Small nucleolar RNAs(snoRNAs)represent a class of non-coding RNAs that play pivotal roles in post-transcriptional RNA processing and modification,thereby contributing significantly to the maintenance of cellular funct...Small nucleolar RNAs(snoRNAs)represent a class of non-coding RNAs that play pivotal roles in post-transcriptional RNA processing and modification,thereby contributing significantly to the maintenance of cellular functions related to protein synthesis.SnoRNAs have been discovered to possess the ability to influence cell fate and alter disease progression,holding immense potential in controlling human diseases.It is suggested that the dysregulation of snoRNAs in cancer exhibits differential expression across various cancer types,stages,metastasis,treatment response and/or prognosis in patients.On the other hand,colorectal cancer(CRC),a prevalent malignancy of the digestive system,is characterized by high incidence and mortality rates,ranking as the third most common cancer type.Recent research indicates that snoRNA dysregulation is associated with CRC,as snoRNA expression significantly differs between normal and cancerous conditions.Consequently,assessing snoRNA expression level and function holds promise for the prognosis and diagnosis of CRC.Nevertheless,current comprehension of the potential roles of snoRNAs in CRC remains limited.This review offers a comprehensive survey of the aberrant regulation of snoRNAs in CRC,providing valuable insights into the discovery of novel biomarkers,therapeutic targets,and potential tools for the diagnosis and treatment of CRC and furnishing critical cues for advancing research into CRC and the judicious selection of therapeutic targets.展开更多
Chronic inflammation is known to increase the risk of gastrointestinal cancers(GICs),the common solid tumors worldwide.Precancerous lesions,such as chronic atrophic inflammation and ulcers,are related to inflammatory ...Chronic inflammation is known to increase the risk of gastrointestinal cancers(GICs),the common solid tumors worldwide.Precancerous lesions,such as chronic atrophic inflammation and ulcers,are related to inflammatory responses in vivo and likely to occur in hyperplasia and tumorigenesis.Unfortunately,due to the lack of effective therapeutic targets,the prognosis of patients with GICs is still unsatisfactory.Interestingly,it is found that six transmembrane epithelial antigens of the prostate(STEAPs),a group of metal reductases,are significantly associated with the progression of malignancies,playing a crucial role in systemic metabolic homeostasis and inflammatory responses.The structure and functions of STEAPs suggest that they are closely related to intracellular oxidative stress,responding to inflammatory reactions.Under the imbalance status of abnormal oxidative stress,STEAP members are involved in cell transformation and the development of GICs by inhibiting or activating inflammatory process.This review focuses on STEAPs in GICs along with exploring their potential molecular regulatory mechanisms,with an aim to provide a theoretical basis for diagnosis and treatment strategies for patients suffering from these types of cancers.展开更多
The sine oculis homeobox homolog(SIX)family,a group of transcription factors characterized by a conserved DNA-binding homology domain,plays a critical role in orchestrating embryonic development and organogenesis acro...The sine oculis homeobox homolog(SIX)family,a group of transcription factors characterized by a conserved DNA-binding homology domain,plays a critical role in orchestrating embryonic development and organogenesis across various organisms,including humans.Comprising six distinct members,from SIX1 to SIX6,each member contributes uniquely to the development and differentiation of diverse tissues and organs,underscoring the versatility of the SIX family.Dysregulation or mutations in SIX genes have been implicated in a spectrum of developmental disorders,as well as in tumor initiation and progression,highlighting their pivotal role in maintaining normal developmental trajectories and cellular functions.Efforts to target the transcriptional complex of the SIX gene family have emerged as a promising strategy to inhibit tumor development.While the development of inhibitors targeting this gene family is still in its early stages,the significant potential of such interventions holds promise for future therapeutic advances.Therefore,this review aimed to comprehensively explore the advancements in understanding the SIX family within gastrointestinal cancers,focusing on its critical role in normal organ development and its implications in gastrointestinal cancers,including gastric,pancreatic,colorectal cancer,and hepatocellular carcinomas.In conclusion,this review deepened the understanding of the functional roles of the SIX family and explored the potential of utilizing this gene family for the diagnosis,prognosis,and treatment of gastrointestinal cancers.展开更多
Ferroptosis is a newly discovered type of cell-regulated death.It is characterized by the accumulation of iron-dependent lipid peroxidation and can be distinguished from other forms of cell-regulated death by differen...Ferroptosis is a newly discovered type of cell-regulated death.It is characterized by the accumulation of iron-dependent lipid peroxidation and can be distinguished from other forms of cell-regulated death by different morphology,biochemistry,and genetics.Recently,studies have shown that ferroptosis is associated with a variety of diseases,including liver,kidney and neurological diseases,as well as cancer.Ferroptosis has been shown to be associated with colorectal epithelial disorders,which can lead to cancerous changes in the gut.However,the potential role of ferroptosis in the occurrence and development of colorectal cancer(CRC)is still controversial.To elucidate the underlying mechanisms of ferroptosis in CRC,this article systematically reviews ferroptosis,and its cellular functions in CRC,for furthering the understanding of the pathogenesis of CRC to aid clinical treatment.展开更多
Colorectal cancer(CRC),the third most common type of cancer worldwide,threaten human health and quality of life.With multidisciplinary,including surgery,chemotherapy and/or radiotherapy,patients with an early diagnosi...Colorectal cancer(CRC),the third most common type of cancer worldwide,threaten human health and quality of life.With multidisciplinary,including surgery,chemotherapy and/or radiotherapy,patients with an early diagnosis of CRC can have a good prognosis.However,metastasis in CRC patients is the main risk factor causing cancer-related death.To elucidate the underlying molecular mechanisms of CRC metastasis is the difficult and research focus on the investigation of the CRC mechanism.On the other hand,the tumor microenvironment(TME)has been confirmed as having an essential role in the tumorigenesis and metastasis of malignancies,including CRCs.Among the different factors in the TME,exosomes as extracellular vesicles,function as bridges in the communication between cancer cells and different components of the TME to promote the progression and metastasis of CRC.MicroRNAs packaged in exosomes can be derived from different sources and transported into the TME to perform oncogenic or tumor-suppressor roles accordingly.This article focuses on CRC exosomes and illustrates their role in regulating the metastasis of CRC,especially through the packaging of miRNAs,to evoke exosomes as novel biomarkers for their impact on the metastasis of CRC progression.展开更多
BACKGROUND Immune cells play an important role in regulating the behavior of tumor cells.According to emerging evidence,six-transmembrane epithelial antigen of the prostate 4(STEAP4)performs a crucial part in tumor mi...BACKGROUND Immune cells play an important role in regulating the behavior of tumor cells.According to emerging evidence,six-transmembrane epithelial antigen of the prostate 4(STEAP4)performs a crucial part in tumor microenvironmental immune response and tumorigenesis,and serves as the potential target for cellular and antibody immunotherapy.However,the immunotherapeutic role of STEAP4 in gastric cancer(GC)remains unclear.AIM To investigate the expression of STEAP4 in GC and its relationship with immune infiltrating cells,and explore the potential value of STEAP4 as an immune prognostic indicator in GC.METHODS The expression level of STEAP4 was characterized by immunohistochemistry in tumors and adjacent non-cancerous samples in 96 GC patients.Tumor Immune Estimation Resource was used to study the correlation between STEAP4 and tumor immune infiltration level and immune infiltration gene signature.R package was used to analyze the relationship between STEAP4 expression and immune and stromal scores in GC(GSE62254)by the ESTIMATE algorithm,and Kaplan-Meier Plotter and Gene Expression Profiling Interactive Analysis were applied to analyze the effect of STEAP4 on clinical prognosis.RESULTS Immunohistochemistry analysis showed that STEAP4 expression was higher in GC tissues than in adjacent tissues,and STEAP4 expression was positively correlated with the clinical stage of GC.In GC,the expression of STEAP4 was positively correlated with the infiltration levels of B cells,CD4+T cells,macrophages,neutrophils,and dendritic cells.The expression level of STEAP4 was strongly correlated with most of the immune markers.In addition,STEAP4 expression was inversely correlated with tumor purity,but correlated with stromal score(r=0.43,P<0.001),immune score(r=0.29,P<0.001)and estimate score(r=0.39,P<0.001).Moreover,stromal,immune,and estimate scores were higher in the STEAP4 high expression group,whereas tumor purity was higher in the STEAP4 Low expression group.The relationship between STEAP4 expression and prognosis of patients with GC was further investigated,and the results showed that high STEAP4 expression was associated with poor overall survival and disease-free survival.In addition,Kaplan-Meier Plotter showed that high expression of STEAP4 was significantly correlated with poor survival of patients with GC.CONCLUSION The current findings suggest an oncogenic role for STEAP4 in GC,with significantly high levels being associated with poor prognosis.Investigation of the GC tumor microenvironment suggests the potential function of STEAP4 is connected with the infiltration of diverse immune cells,which may contribute to the regulation of the tumor microenvironment.In conclusion,STEAP4 may serve as a potential therapeutic target for GC to improve the immune infiltration,as well as serve as a prognostic biomarker for judging the prognosis and immune infiltration status of GC.展开更多
BACKGROUND Ras suppressor 1(RSU1),a highly conserved protein,plays an important role in actin cytoskeleton remodeling and cell-extracellular matrix adhesion.Aberration of RSU1 activity can cause changes in cell adhesi...BACKGROUND Ras suppressor 1(RSU1),a highly conserved protein,plays an important role in actin cytoskeleton remodeling and cell-extracellular matrix adhesion.Aberration of RSU1 activity can cause changes in cell adhesion and migration,thereby enhancing tumor proliferation and metastasis.However,the correlation between RSU1 and gastrointestinal cancers(GICs),as well as its prognostic role related to tumor-infiltrating immune cells(TIICs)remains unclear.AIM To shows RSU1 plays a potential promoting role in facilitating tumor immune escape in GIC.METHODS Differential expression of RSU1 in different tumors and their corresponding normal tissues was evaluated by exploring the Gene Expression Profiling Interactive Analysis(GEPIA)dataset.The correlation between RSU1 expression and prognosis of GIC cancer patients was evaluated by Kaplan-Meier plotter.Then,RSU1-correlated genes were screened and functionally characterized via enrichment analysis.The correlation between RSU1 and TIICs was further characterized using the Tumor Immune Estimation Resource(TIMER).In addition,the correlation between RSU1 and immune cell surface molecules was also analyzed by TIMER.RESULTS High RSU1 expression was associated with poor overall survival of gastric cancer patients,exhibiting a hazard ratio(HR)=1.36,first progression HR=1.53,and post progression survival HR=1.6.Specifically,high RSU1 Levels were associated with prognosis of gastric cancer in females,T4 and N3 stages,and Her-2-negative subtypes.Regarding immune-infiltrating cells,RSU1 expression level was positively correlated with infiltration of CD4+T cells,macrophages,neutrophils,and dendritic cells(DCs)in colorectal adenocarcinoma and stomach adenocarcinoma.RSU1 expression was also predicted to be strongly correlated with immune marker sets in M2 macrophage,DCs and T cell exhaustion in GICs.CONCLUSION In gastrointestinal cancers,RSU1 is increased in tumor tissues,and predicts poor survival of patients.Increased RSU1 may be involved in promoting macrophage polarization,DC infiltration,and T cell exhaustion,inducing tumor immune escape and the development of tumors in GICs.We suggest that RSU1 is a promising prognostic biomarker reflecting immune infiltration level of GICs,as well as a potential therapeutic target for precision treatment through improving the immune response.展开更多
Gastric cancer(GC)is the fifth most diagnosed cancer and the third leading causeof cancer-related death worldwide.Although progress has been made in diagnosis,surgical resection,systemic chemotherapy,and immunotherapy...Gastric cancer(GC)is the fifth most diagnosed cancer and the third leading causeof cancer-related death worldwide.Although progress has been made in diagnosis,surgical resection,systemic chemotherapy,and immunotherapy,patientswith GC still have a poor prognosis.The overall 5-year survival rate in patientswith advanced GC is less than 5%.The FOXO subfamily,of the forkhead boxfamily of transcription factors,consists of four members,FOXO1,FOXO3,FOXO4,and FOXO6.This subfamily plays an important role in many cellular processes,such as cell cycle,cell growth,apoptosis,autophagy,stress resistance,protectionfrom aggregate toxicity,DNA repair,tumor suppression,and metabolism,in bothnormal tissue and malignant tumors.Various studies support a role for FOXOs astumor suppressors based on their ability to inhibit angiogenesis and metastasis,and promote apoptosis,yet several other studies have shown that FOXOs mightalso promote tumor progression in certain circumstances.To elucidate the diverseroles of FOXOs in GC,this article systematically reviews the cellular functions ofFOXOs in GC to determine potential therapeutic targets and treatment strategiesfor patients with GC.展开更多
BACKGROUND Immune cells play a role in the regulation of tumor cell behavior, and accumulating evidence supports their significance in predicting outcomes and therapeutic efficacy in colorectal cancers(CRC). Human six...BACKGROUND Immune cells play a role in the regulation of tumor cell behavior, and accumulating evidence supports their significance in predicting outcomes and therapeutic efficacy in colorectal cancers(CRC). Human six-transmembrane epithelial antigen of the prostate(STEAP) proteins have been recognized and utilized as promising targets for cell-and antibody-based immunotherapy. One STEAP family member, STEAP4, is expected to be an attractive biomarker for the immunotherapy of prostate and breast cancer. However, the immunotherapeutic role of STEAP4 for colorectal carcinomas has not been demonstrated.AIM To explore the expression pattern of STEAPs in CRC and their relationship with immune infiltration, and investigate the potential utilization of STEAPs as novel prognostic indicators in colorectal carcinomas.METHODS The expression level of STEAPs in CRC was evaluated using various openresource databases and online tools to explore the expression characteristics and prognostic significance of STEAPs, as well as their correlation with immunerelated biomarkers, such as immune infiltration. Immunohistochemical(IHC) experiments were subsequently performed to verify the database conclusions.RESULTS The levels of STEAPs in CRC were inconsistent. The expression of STEAPs 1-3 in CRC was not significantly different from that in normal tissues. However,STEAP4 mRNA levels were significantly lower in CRC than in normal tissue and were positively correlated with immune-related biomarkers, such as immune cell infiltration, immune stimulation, major histocompatibility complex levels, and chemokines. Interestingly, the expression of STEAP4 in microsatellite instability-high CRC subtype was higher than that in microsatellite stability subtype. IHC staining was performed on colon cancer tissue samples and showed that high expression of STEAP4 in adjacent tissues positively correlated with immune-related biomarkers, including MLH1, MLH6, and PMS2, but negatively correlated with programmed death ligand 1, to varying degrees.CONCLUSION Our results provide an analysis of the expression of STEAP family members in CRC. Among different STEAP family members, STEAP4 plays a different role in CRC compared to STEAPs 1-3. In CRC, STEAP4 expression is not only lower than that in normal tissues, but it is also positively correlated with immune infiltration and immune-related biomarkers. These findings suggest that STEAP4 may be a potential biomarker for predicting CRC immune infiltration status.展开更多
BACKGROUND Abnormal expression patterns of mucin 2(MUC2)have been reported in a variety of malignant tumors and precancerous lesions.Reduced MUC2 expression in the intestinal mucosa,caused by various pathogenic factor...BACKGROUND Abnormal expression patterns of mucin 2(MUC2)have been reported in a variety of malignant tumors and precancerous lesions.Reduced MUC2 expression in the intestinal mucosa,caused by various pathogenic factors,is related to mechanical dysfunction of the intestinal mucosa barrier and increased intestinal mucosal permeability.However,the relationship between MUC2 and the intestinal mucosal barrier in patients with colorectal cancer(CRC)is not clear.AIM To explore the relationship between MUC2 and intestinal mucosal barrier by characterizing the multiple expression patterns of MUC2 in CRC.METHODS Immunohistochemical staining was performed on intestinal tissue specimens from 100 CRC patients,including both cancer tissues and adjacent normal tissues.Enzyme-linked immunosorbent assays were performed on preoperative sera from 66 CRC patients and 20 normal sera to detect the serum levels of MUC2,diamine oxide(DAO),and D-lactate(D-LAC).The relationship between MUC2 expression and clinical parameters was calculated by theχ2 test or Fisher’s exact test.Prognostic value of MUC2 was evaluated by Kaplan-Meier curve and log-rank tests.RESULTS Immunohistochemical staining of 100 CRC tissues showed that the expression of MUC2 in cancer tissues was lower than that in normal tissues(54%vs 79%,P<0.05),and it was correlated with tumor-node-metastasis(TNM)stage and lymph node metastasis in CRC patients(P<0.05).However,the serum level of MUC2 in CRC patients was higher than that in normal controls,and was positively associated with serum levels of human DAO(χ2=3.957,P<0.05)and D-LAC(χ^(2)=7.236,P<0.05),which are the biomarkers of the functional status of the intestinal mucosal barrier.And the serum level of MUC2 was correlated with TNM stage,tumor type,and distant metastasis in CRC patients(P<0.05).Kaplan-Meier curves showed that decreased MUC2 expression in CRC tissues predicted a poor survival.CONCLUSION MUC2 in tissues may play a protective role by participating in the intestinal mucosal barrier and can be used as an indicator to evaluate the prognosis of CRC patients.展开更多
BACKGROUND Several genes,important for development,are reduced or silenced in adulthood,and their abnormal expression has been related to the occurrence and development of malignant tumors.Human sine oculis homeobox h...BACKGROUND Several genes,important for development,are reduced or silenced in adulthood,and their abnormal expression has been related to the occurrence and development of malignant tumors.Human sine oculis homeobox homolog(SIX)proteins belong to the homeobox family and play important roles in the development of different organs.Importantly,SIXs are predicted to have chromatin-binding and DNA-binding transcription factor activity with reported roles in cancers.However,a comprehensive analysis of SIXs in colorectal cancers(CRCs)has not been performed.AIM To explore the expression pattern of six SIX proteins in CRCs and their relationship with the clinicopathological parameters of CRC patients as well as investigate the potential utilization of SIXs as novel prognostic indicators in CRCs.METHODS The expression level of SIXs in normal tissues of different organs and related cancerous tissues was analyzed in the Human Protein Atlas.Kaplan-Meier Plotter and GEPIA2 were used to analyze the prognostic values of SIXs.To analyze the potential signaling pathways with SIX family involvement,LinkedOmics was used to perform Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses of SIX4-related genes.Subsequently,immunohistochemical experiments were performed on CRC tissues and adjacent normal tissues,and we examined the SIX4 expression level in 87 pairs of patients with tissue microarray.The relationship between SIX4 and clinicopathological parameters in CRC patients was tested using theχ2 test and Fisher’s exact probability to verify the results of the database analysis.RESULTS The RNA levels of SIX1-4 and SIX6 were relatively low in normal human tissues,while SIX5 was highly expressed at both the RNA and protein levels.However,the protein level of SIX4 was found to be elevated in various malignancies.In CRC tissues,SIX1,SIX2 and SIX4 were elevated in cancer tissues compared with adjacent normal tissue.Among all SIXs,a high level of SIX4 was found to be associated with poor overall and disease-free survival in patients with CRC.For different clinicopathological parameters,increased SIX4 expression was positively correlated with advanced CRC.The top 50 SIX4-related genes were involved with oxidative phosphorylation and the respiratory chain signaling pathways.CONCLUSION The current results provided a comprehensive analysis of the expression and prognostic values of SIX family members in CRC.Among different SIXs,SIX4 plays an oncogenic role in CRC to promote the development of malignancy.In CRC,SIX4 mRNA and protein expression is higher than that in normal tissues and associated with shorter CRC patient survival,suggesting that SIX4 may be a potential therapeutic target for treatment of CRC patients.展开更多
Objective:To study the expression and significance of TNF-transcription factor M1(FoxM1)in bladder cancer and cystitis glandularis(CG).Methods:A total of 30 patients with bladder cancer admitted to our hospital and re...Objective:To study the expression and significance of TNF-transcription factor M1(FoxM1)in bladder cancer and cystitis glandularis(CG).Methods:A total of 30 patients with bladder cancer admitted to our hospital and received surgical treatment from February 2017 to February 2019 were included for the study.During surgery,bladder cancer tissues and normal bladder tissues(tissues more than 5cm away from the cancer tissue center)were collected.Meanwhile,we retained 30 CG tissues from 30 CG patients who received surgical treatment in our hospital at the same time.Bladder cancer cell lines RT4 and BIU87 were cultured and treated with TNF-αat different concentrations(0nM,1nM,5nM,10nM).The expressions of TNF-αand FoxM1 in different bladder tissues were analyzed,and the effects of different concentrations of TNF-αon the expressions of FoxM1 in bladder cancer cell lines and cyclin B1 and cyclin D1 in bladder cancer cell lines were analyzed.Results:The expression levels of TNF-αand FoxM1 in normal bladder,CG and bladder cancer tissues were gradually increased,and univariate analysis of variance showed that the differences between groups were statistically significant(all P<0.05).FoxM1 expression in bladder cancer cell lines treated with TNF-αat concentrations of 0nM,1nM,5nM and 10nM showed a gradual increase trend,and one-way anova showed that the difference between the groups was statistically significant(all P<0.05).After the treatment of bladder cancer cell lines with TNF-αat concentrations of 0nM,1nM,5nM and 10nM,the expression of cyclin B1 and cyclin D1 showed a gradually increasing trend,and one-way anova showed that the difference between groups was statistically significant(all P<0.05).Conclusion:TNF-αmay play a crucial role in the occurrence and development of CG by regulating the expression of transcription factor FoxM1,and then affecting the expression of cyclin B1 and cyclin D1,which is worthy of clinical attention.展开更多
基金the National Natural Science Foundation of China,No.82273457Guangdong Basic and Applied Basic Research Foundation,No.2021A1515012180 and No.2023A1515012762+1 种基金Special Grant for Key Area Programs of Guangdong Department of Education,No.2021ZDZX2040and Science and Technology Special Project of Guangdong Province,No.210715216902829.
文摘Small nucleolar RNAs(snoRNAs)represent a class of non-coding RNAs that play pivotal roles in post-transcriptional RNA processing and modification,thereby contributing significantly to the maintenance of cellular functions related to protein synthesis.SnoRNAs have been discovered to possess the ability to influence cell fate and alter disease progression,holding immense potential in controlling human diseases.It is suggested that the dysregulation of snoRNAs in cancer exhibits differential expression across various cancer types,stages,metastasis,treatment response and/or prognosis in patients.On the other hand,colorectal cancer(CRC),a prevalent malignancy of the digestive system,is characterized by high incidence and mortality rates,ranking as the third most common cancer type.Recent research indicates that snoRNA dysregulation is associated with CRC,as snoRNA expression significantly differs between normal and cancerous conditions.Consequently,assessing snoRNA expression level and function holds promise for the prognosis and diagnosis of CRC.Nevertheless,current comprehension of the potential roles of snoRNAs in CRC remains limited.This review offers a comprehensive survey of the aberrant regulation of snoRNAs in CRC,providing valuable insights into the discovery of novel biomarkers,therapeutic targets,and potential tools for the diagnosis and treatment of CRC and furnishing critical cues for advancing research into CRC and the judicious selection of therapeutic targets.
基金the National Natural Science Foundation of China,No.82273457the Natural Science Foundation of Guangdong Province,No.2021A1515012180,2023A1515012762 and No.2019A1515010962+1 种基金Special Grant for Key Area Programs of Guangdong Department of Education,No.2021ZDZX2040Science and Technology Special Project of Guangdong Province,No.210715216902829.
文摘Chronic inflammation is known to increase the risk of gastrointestinal cancers(GICs),the common solid tumors worldwide.Precancerous lesions,such as chronic atrophic inflammation and ulcers,are related to inflammatory responses in vivo and likely to occur in hyperplasia and tumorigenesis.Unfortunately,due to the lack of effective therapeutic targets,the prognosis of patients with GICs is still unsatisfactory.Interestingly,it is found that six transmembrane epithelial antigens of the prostate(STEAPs),a group of metal reductases,are significantly associated with the progression of malignancies,playing a crucial role in systemic metabolic homeostasis and inflammatory responses.The structure and functions of STEAPs suggest that they are closely related to intracellular oxidative stress,responding to inflammatory reactions.Under the imbalance status of abnormal oxidative stress,STEAP members are involved in cell transformation and the development of GICs by inhibiting or activating inflammatory process.This review focuses on STEAPs in GICs along with exploring their potential molecular regulatory mechanisms,with an aim to provide a theoretical basis for diagnosis and treatment strategies for patients suffering from these types of cancers.
基金Supported by the National Natural Science Foundation of China,No.82273457the Natural Science Foundation of Guangdong Province,No.2023A1515012762 and No.2021A1515010846+1 种基金Special Grant for Key Area Programs of Guangdong Department of Education,No.2021ZDZX2040Science and Technology Special Project of Guangdong Province,No.210715216902829.
文摘The sine oculis homeobox homolog(SIX)family,a group of transcription factors characterized by a conserved DNA-binding homology domain,plays a critical role in orchestrating embryonic development and organogenesis across various organisms,including humans.Comprising six distinct members,from SIX1 to SIX6,each member contributes uniquely to the development and differentiation of diverse tissues and organs,underscoring the versatility of the SIX family.Dysregulation or mutations in SIX genes have been implicated in a spectrum of developmental disorders,as well as in tumor initiation and progression,highlighting their pivotal role in maintaining normal developmental trajectories and cellular functions.Efforts to target the transcriptional complex of the SIX gene family have emerged as a promising strategy to inhibit tumor development.While the development of inhibitors targeting this gene family is still in its early stages,the significant potential of such interventions holds promise for future therapeutic advances.Therefore,this review aimed to comprehensively explore the advancements in understanding the SIX family within gastrointestinal cancers,focusing on its critical role in normal organ development and its implications in gastrointestinal cancers,including gastric,pancreatic,colorectal cancer,and hepatocellular carcinomas.In conclusion,this review deepened the understanding of the functional roles of the SIX family and explored the potential of utilizing this gene family for the diagnosis,prognosis,and treatment of gastrointestinal cancers.
基金National Natural Science Foundation of China,No.81501539Natural Science Foundation of Guangdong Province,No.2021A1515012180 and 2016A030312008+2 种基金Special Grant for Key Area Programs of Guangdong Department of Education,No.2021ZDZX2004Science and Technology Special Project of Guangdong Province,No.210715216902829Dengfeng Project”for the Construction of High-level Hospitals in Guangdong Province-First Affiliated Hospital of Shantou University College Supporting Funding,No.202003-10.
文摘Ferroptosis is a newly discovered type of cell-regulated death.It is characterized by the accumulation of iron-dependent lipid peroxidation and can be distinguished from other forms of cell-regulated death by different morphology,biochemistry,and genetics.Recently,studies have shown that ferroptosis is associated with a variety of diseases,including liver,kidney and neurological diseases,as well as cancer.Ferroptosis has been shown to be associated with colorectal epithelial disorders,which can lead to cancerous changes in the gut.However,the potential role of ferroptosis in the occurrence and development of colorectal cancer(CRC)is still controversial.To elucidate the underlying mechanisms of ferroptosis in CRC,this article systematically reviews ferroptosis,and its cellular functions in CRC,for furthering the understanding of the pathogenesis of CRC to aid clinical treatment.
基金Supported by National Natural Science Foundation of China,No. 82273457Natural Science Foundation of Guangdong Province,No. 2021A1515012180 and 2016A030312008+1 种基金Special Grant for Key Area Programs of Guangdong Department of Education,No. 2021ZDZX2040Science and Technology Special Project of Guangdong Province,No. 210715216902829
文摘Colorectal cancer(CRC),the third most common type of cancer worldwide,threaten human health and quality of life.With multidisciplinary,including surgery,chemotherapy and/or radiotherapy,patients with an early diagnosis of CRC can have a good prognosis.However,metastasis in CRC patients is the main risk factor causing cancer-related death.To elucidate the underlying molecular mechanisms of CRC metastasis is the difficult and research focus on the investigation of the CRC mechanism.On the other hand,the tumor microenvironment(TME)has been confirmed as having an essential role in the tumorigenesis and metastasis of malignancies,including CRCs.Among the different factors in the TME,exosomes as extracellular vesicles,function as bridges in the communication between cancer cells and different components of the TME to promote the progression and metastasis of CRC.MicroRNAs packaged in exosomes can be derived from different sources and transported into the TME to perform oncogenic or tumor-suppressor roles accordingly.This article focuses on CRC exosomes and illustrates their role in regulating the metastasis of CRC,especially through the packaging of miRNAs,to evoke exosomes as novel biomarkers for their impact on the metastasis of CRC progression.
基金the National Natural Science Foundation of China,No.82273457 and No.81501539Guangdong Basic and Applied Basic Research Foundation,No.2023A1515012762 and No.2021A1515012180+1 种基金Special Grant for Key Area Programs of Guangdong Department of Education,No.2021ZDZX2040Science and Technology Special Project of Guangdong Province,No.210715216902829.
文摘BACKGROUND Immune cells play an important role in regulating the behavior of tumor cells.According to emerging evidence,six-transmembrane epithelial antigen of the prostate 4(STEAP4)performs a crucial part in tumor microenvironmental immune response and tumorigenesis,and serves as the potential target for cellular and antibody immunotherapy.However,the immunotherapeutic role of STEAP4 in gastric cancer(GC)remains unclear.AIM To investigate the expression of STEAP4 in GC and its relationship with immune infiltrating cells,and explore the potential value of STEAP4 as an immune prognostic indicator in GC.METHODS The expression level of STEAP4 was characterized by immunohistochemistry in tumors and adjacent non-cancerous samples in 96 GC patients.Tumor Immune Estimation Resource was used to study the correlation between STEAP4 and tumor immune infiltration level and immune infiltration gene signature.R package was used to analyze the relationship between STEAP4 expression and immune and stromal scores in GC(GSE62254)by the ESTIMATE algorithm,and Kaplan-Meier Plotter and Gene Expression Profiling Interactive Analysis were applied to analyze the effect of STEAP4 on clinical prognosis.RESULTS Immunohistochemistry analysis showed that STEAP4 expression was higher in GC tissues than in adjacent tissues,and STEAP4 expression was positively correlated with the clinical stage of GC.In GC,the expression of STEAP4 was positively correlated with the infiltration levels of B cells,CD4+T cells,macrophages,neutrophils,and dendritic cells.The expression level of STEAP4 was strongly correlated with most of the immune markers.In addition,STEAP4 expression was inversely correlated with tumor purity,but correlated with stromal score(r=0.43,P<0.001),immune score(r=0.29,P<0.001)and estimate score(r=0.39,P<0.001).Moreover,stromal,immune,and estimate scores were higher in the STEAP4 high expression group,whereas tumor purity was higher in the STEAP4 Low expression group.The relationship between STEAP4 expression and prognosis of patients with GC was further investigated,and the results showed that high STEAP4 expression was associated with poor overall survival and disease-free survival.In addition,Kaplan-Meier Plotter showed that high expression of STEAP4 was significantly correlated with poor survival of patients with GC.CONCLUSION The current findings suggest an oncogenic role for STEAP4 in GC,with significantly high levels being associated with poor prognosis.Investigation of the GC tumor microenvironment suggests the potential function of STEAP4 is connected with the infiltration of diverse immune cells,which may contribute to the regulation of the tumor microenvironment.In conclusion,STEAP4 may serve as a potential therapeutic target for GC to improve the immune infiltration,as well as serve as a prognostic biomarker for judging the prognosis and immune infiltration status of GC.
基金Supported by the National Natural Science Foundation of China,No.82273457the Natural Science Foundation of Guangdong Province,No.2023A1515012762+2 种基金and 2021A1515012180Special Grant for Key Area Programs of Guangdong Department of Education,No.2021ZDZX2040Science and Technology Special Project of Guangdong Province,No.210715216902829.
文摘BACKGROUND Ras suppressor 1(RSU1),a highly conserved protein,plays an important role in actin cytoskeleton remodeling and cell-extracellular matrix adhesion.Aberration of RSU1 activity can cause changes in cell adhesion and migration,thereby enhancing tumor proliferation and metastasis.However,the correlation between RSU1 and gastrointestinal cancers(GICs),as well as its prognostic role related to tumor-infiltrating immune cells(TIICs)remains unclear.AIM To shows RSU1 plays a potential promoting role in facilitating tumor immune escape in GIC.METHODS Differential expression of RSU1 in different tumors and their corresponding normal tissues was evaluated by exploring the Gene Expression Profiling Interactive Analysis(GEPIA)dataset.The correlation between RSU1 expression and prognosis of GIC cancer patients was evaluated by Kaplan-Meier plotter.Then,RSU1-correlated genes were screened and functionally characterized via enrichment analysis.The correlation between RSU1 and TIICs was further characterized using the Tumor Immune Estimation Resource(TIMER).In addition,the correlation between RSU1 and immune cell surface molecules was also analyzed by TIMER.RESULTS High RSU1 expression was associated with poor overall survival of gastric cancer patients,exhibiting a hazard ratio(HR)=1.36,first progression HR=1.53,and post progression survival HR=1.6.Specifically,high RSU1 Levels were associated with prognosis of gastric cancer in females,T4 and N3 stages,and Her-2-negative subtypes.Regarding immune-infiltrating cells,RSU1 expression level was positively correlated with infiltration of CD4+T cells,macrophages,neutrophils,and dendritic cells(DCs)in colorectal adenocarcinoma and stomach adenocarcinoma.RSU1 expression was also predicted to be strongly correlated with immune marker sets in M2 macrophage,DCs and T cell exhaustion in GICs.CONCLUSION In gastrointestinal cancers,RSU1 is increased in tumor tissues,and predicts poor survival of patients.Increased RSU1 may be involved in promoting macrophage polarization,DC infiltration,and T cell exhaustion,inducing tumor immune escape and the development of tumors in GICs.We suggest that RSU1 is a promising prognostic biomarker reflecting immune infiltration level of GICs,as well as a potential therapeutic target for precision treatment through improving the immune response.
基金National Natural Science Foundation of China,No.81501539Natural Science Foundation of Guangdong Province,No.2021A1515012180 and No.2016A030312008+2 种基金Science and Technology Planning Project of Shantou,China,No.200617105260368“Dengfeng Project”for the Construction of High-level Hospitals in Guangdong Province—the First Affiliated Hospital of Shantou University College Supporting Funding,No.202003-10Guangdong Provincial Undergraduate Innovation and Entrepreneurship Training Project,No.S202010560121.
文摘Gastric cancer(GC)is the fifth most diagnosed cancer and the third leading causeof cancer-related death worldwide.Although progress has been made in diagnosis,surgical resection,systemic chemotherapy,and immunotherapy,patientswith GC still have a poor prognosis.The overall 5-year survival rate in patientswith advanced GC is less than 5%.The FOXO subfamily,of the forkhead boxfamily of transcription factors,consists of four members,FOXO1,FOXO3,FOXO4,and FOXO6.This subfamily plays an important role in many cellular processes,such as cell cycle,cell growth,apoptosis,autophagy,stress resistance,protectionfrom aggregate toxicity,DNA repair,tumor suppression,and metabolism,in bothnormal tissue and malignant tumors.Various studies support a role for FOXOs astumor suppressors based on their ability to inhibit angiogenesis and metastasis,and promote apoptosis,yet several other studies have shown that FOXOs mightalso promote tumor progression in certain circumstances.To elucidate the diverseroles of FOXOs in GC,this article systematically reviews the cellular functions ofFOXOs in GC to determine potential therapeutic targets and treatment strategiesfor patients with GC.
基金Supported by the National Natural Science Foundation of China,No. 81501539the Natural Science Foundation of Guangdong Province,No. 2021A1515012180 and 2016A030312008+2 种基金the Special Grant for Key Area Programs of Guangdong Department of Education,No. 2021ZDZX2004the Science and Technology Special Project of Guangdong Province,No. 210715216902829“Dengfeng Project” for the Construction of High-level Hospitals in Guangdong Province-First Affiliated Hospital of Shantou University College Supporting Funding,No. 202003-10。
文摘BACKGROUND Immune cells play a role in the regulation of tumor cell behavior, and accumulating evidence supports their significance in predicting outcomes and therapeutic efficacy in colorectal cancers(CRC). Human six-transmembrane epithelial antigen of the prostate(STEAP) proteins have been recognized and utilized as promising targets for cell-and antibody-based immunotherapy. One STEAP family member, STEAP4, is expected to be an attractive biomarker for the immunotherapy of prostate and breast cancer. However, the immunotherapeutic role of STEAP4 for colorectal carcinomas has not been demonstrated.AIM To explore the expression pattern of STEAPs in CRC and their relationship with immune infiltration, and investigate the potential utilization of STEAPs as novel prognostic indicators in colorectal carcinomas.METHODS The expression level of STEAPs in CRC was evaluated using various openresource databases and online tools to explore the expression characteristics and prognostic significance of STEAPs, as well as their correlation with immunerelated biomarkers, such as immune infiltration. Immunohistochemical(IHC) experiments were subsequently performed to verify the database conclusions.RESULTS The levels of STEAPs in CRC were inconsistent. The expression of STEAPs 1-3 in CRC was not significantly different from that in normal tissues. However,STEAP4 mRNA levels were significantly lower in CRC than in normal tissue and were positively correlated with immune-related biomarkers, such as immune cell infiltration, immune stimulation, major histocompatibility complex levels, and chemokines. Interestingly, the expression of STEAP4 in microsatellite instability-high CRC subtype was higher than that in microsatellite stability subtype. IHC staining was performed on colon cancer tissue samples and showed that high expression of STEAP4 in adjacent tissues positively correlated with immune-related biomarkers, including MLH1, MLH6, and PMS2, but negatively correlated with programmed death ligand 1, to varying degrees.CONCLUSION Our results provide an analysis of the expression of STEAP family members in CRC. Among different STEAP family members, STEAP4 plays a different role in CRC compared to STEAPs 1-3. In CRC, STEAP4 expression is not only lower than that in normal tissues, but it is also positively correlated with immune infiltration and immune-related biomarkers. These findings suggest that STEAP4 may be a potential biomarker for predicting CRC immune infiltration status.
基金Supported by National Natural Science Foundation of China,No.81501539the Natural Science Foundation of Guangdong Province,China,No.2016A030312008+2 种基金Science and Technology Planning Project of Shantou,China,No.200617105260368Medical Scientific Research Foundation of Guangdong,China,No.A2020627“Dengfeng Project”for the Construction of High-level Hospital in Guangdong Province-The First Affiliated Hospital of Shantou University College Supporting Funding,No.202003-10.
文摘BACKGROUND Abnormal expression patterns of mucin 2(MUC2)have been reported in a variety of malignant tumors and precancerous lesions.Reduced MUC2 expression in the intestinal mucosa,caused by various pathogenic factors,is related to mechanical dysfunction of the intestinal mucosa barrier and increased intestinal mucosal permeability.However,the relationship between MUC2 and the intestinal mucosal barrier in patients with colorectal cancer(CRC)is not clear.AIM To explore the relationship between MUC2 and intestinal mucosal barrier by characterizing the multiple expression patterns of MUC2 in CRC.METHODS Immunohistochemical staining was performed on intestinal tissue specimens from 100 CRC patients,including both cancer tissues and adjacent normal tissues.Enzyme-linked immunosorbent assays were performed on preoperative sera from 66 CRC patients and 20 normal sera to detect the serum levels of MUC2,diamine oxide(DAO),and D-lactate(D-LAC).The relationship between MUC2 expression and clinical parameters was calculated by theχ2 test or Fisher’s exact test.Prognostic value of MUC2 was evaluated by Kaplan-Meier curve and log-rank tests.RESULTS Immunohistochemical staining of 100 CRC tissues showed that the expression of MUC2 in cancer tissues was lower than that in normal tissues(54%vs 79%,P<0.05),and it was correlated with tumor-node-metastasis(TNM)stage and lymph node metastasis in CRC patients(P<0.05).However,the serum level of MUC2 in CRC patients was higher than that in normal controls,and was positively associated with serum levels of human DAO(χ2=3.957,P<0.05)and D-LAC(χ^(2)=7.236,P<0.05),which are the biomarkers of the functional status of the intestinal mucosal barrier.And the serum level of MUC2 was correlated with TNM stage,tumor type,and distant metastasis in CRC patients(P<0.05).Kaplan-Meier curves showed that decreased MUC2 expression in CRC tissues predicted a poor survival.CONCLUSION MUC2 in tissues may play a protective role by participating in the intestinal mucosal barrier and can be used as an indicator to evaluate the prognosis of CRC patients.
基金Supported by the National Natural Science Foundation of China,No.81501539the Natural Science Foundation of Guangdong Province,No.2021A1515012180 and 2016A030312008+2 种基金Special Grant for Key Area Programs of Guangdong Department of Education,No.2021ZDZX2004Science and Technology Special Project of Guangdong Province,No.210715216902829“Dengfeng Project”for the construction of high-level hospitals in Guangdong Province-First Affiliated Hospital of Shantou University College Supporting Funding,No.202003-10.
文摘BACKGROUND Several genes,important for development,are reduced or silenced in adulthood,and their abnormal expression has been related to the occurrence and development of malignant tumors.Human sine oculis homeobox homolog(SIX)proteins belong to the homeobox family and play important roles in the development of different organs.Importantly,SIXs are predicted to have chromatin-binding and DNA-binding transcription factor activity with reported roles in cancers.However,a comprehensive analysis of SIXs in colorectal cancers(CRCs)has not been performed.AIM To explore the expression pattern of six SIX proteins in CRCs and their relationship with the clinicopathological parameters of CRC patients as well as investigate the potential utilization of SIXs as novel prognostic indicators in CRCs.METHODS The expression level of SIXs in normal tissues of different organs and related cancerous tissues was analyzed in the Human Protein Atlas.Kaplan-Meier Plotter and GEPIA2 were used to analyze the prognostic values of SIXs.To analyze the potential signaling pathways with SIX family involvement,LinkedOmics was used to perform Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses of SIX4-related genes.Subsequently,immunohistochemical experiments were performed on CRC tissues and adjacent normal tissues,and we examined the SIX4 expression level in 87 pairs of patients with tissue microarray.The relationship between SIX4 and clinicopathological parameters in CRC patients was tested using theχ2 test and Fisher’s exact probability to verify the results of the database analysis.RESULTS The RNA levels of SIX1-4 and SIX6 were relatively low in normal human tissues,while SIX5 was highly expressed at both the RNA and protein levels.However,the protein level of SIX4 was found to be elevated in various malignancies.In CRC tissues,SIX1,SIX2 and SIX4 were elevated in cancer tissues compared with adjacent normal tissue.Among all SIXs,a high level of SIX4 was found to be associated with poor overall and disease-free survival in patients with CRC.For different clinicopathological parameters,increased SIX4 expression was positively correlated with advanced CRC.The top 50 SIX4-related genes were involved with oxidative phosphorylation and the respiratory chain signaling pathways.CONCLUSION The current results provided a comprehensive analysis of the expression and prognostic values of SIX family members in CRC.Among different SIXs,SIX4 plays an oncogenic role in CRC to promote the development of malignancy.In CRC,SIX4 mRNA and protein expression is higher than that in normal tissues and associated with shorter CRC patient survival,suggesting that SIX4 may be a potential therapeutic target for treatment of CRC patients.
基金Medical science and technology research in Guangdong province(B2018106).
文摘Objective:To study the expression and significance of TNF-transcription factor M1(FoxM1)in bladder cancer and cystitis glandularis(CG).Methods:A total of 30 patients with bladder cancer admitted to our hospital and received surgical treatment from February 2017 to February 2019 were included for the study.During surgery,bladder cancer tissues and normal bladder tissues(tissues more than 5cm away from the cancer tissue center)were collected.Meanwhile,we retained 30 CG tissues from 30 CG patients who received surgical treatment in our hospital at the same time.Bladder cancer cell lines RT4 and BIU87 were cultured and treated with TNF-αat different concentrations(0nM,1nM,5nM,10nM).The expressions of TNF-αand FoxM1 in different bladder tissues were analyzed,and the effects of different concentrations of TNF-αon the expressions of FoxM1 in bladder cancer cell lines and cyclin B1 and cyclin D1 in bladder cancer cell lines were analyzed.Results:The expression levels of TNF-αand FoxM1 in normal bladder,CG and bladder cancer tissues were gradually increased,and univariate analysis of variance showed that the differences between groups were statistically significant(all P<0.05).FoxM1 expression in bladder cancer cell lines treated with TNF-αat concentrations of 0nM,1nM,5nM and 10nM showed a gradual increase trend,and one-way anova showed that the difference between the groups was statistically significant(all P<0.05).After the treatment of bladder cancer cell lines with TNF-αat concentrations of 0nM,1nM,5nM and 10nM,the expression of cyclin B1 and cyclin D1 showed a gradually increasing trend,and one-way anova showed that the difference between groups was statistically significant(all P<0.05).Conclusion:TNF-αmay play a crucial role in the occurrence and development of CG by regulating the expression of transcription factor FoxM1,and then affecting the expression of cyclin B1 and cyclin D1,which is worthy of clinical attention.
