Studies have shown that gut microbiota metabolites can enter the central nervous system via the blood-spinal cord barrier and cause neuroinflammation, thus constituting secondary injury after spinal cord injury. To in...Studies have shown that gut microbiota metabolites can enter the central nervous system via the blood-spinal cord barrier and cause neuroinflammation, thus constituting secondary injury after spinal cord injury. To investigate the correlation between gut microbiota and metabolites and the possible mechanism underlying the effects of gut microbiota on secondary injury after spinal cord injury, in this study, we established mouse models of T8–T10 traumatic spinal cord injury. We used 16 S rRNA gene amplicon sequencing and metabolomics to reveal the changes in gut microbiota and metabolites in fecal samples from the mouse model. Results showed a severe gut microbiota disturbance after spinal cord injury, which included marked increases in pro-inflammatory bacteria, such as Shigella, Bacteroides, Rikenella, Staphylococcus, and Mucispirillum and decreases in anti-inflammatory bacteria, such as Lactobacillus, Allobaculum, and Sutterella. Meanwhile, we identified 27 metabolites that decreased and 320 metabolites that increased in the injured spinal cord. Combined with pathway enrichment analysis, five markedly differential amino acids(L-leucine, L-methionine, L-phenylalanine, L-isoleucine and L-valine) were screened out, which play a pivotal role in activating oxidative stress and inflammatory responses following spinal cord injury. Integrated correlation analysis indicated that the alteration of gut microbiota was related to the differences in amino acids, which suggests that disturbances in gut microbiota might participate in the secondary injury through the accumulation of partial metabolites that activate oxidative stress and inflammatory responses. Findings from this study provide a new theoretical basis for improving the secondary injury after spinal cord injury through fecal microbial transplantation.展开更多
AIM: To investigate p53 mutation and p21 expression in hepatocarcinogenesis induced by hepatitis B virus (HBV) and aflatoxin B1 (AFB1) in tree shrews, and to reveal the role of these genes in hepatocarcinogenesis.METH...AIM: To investigate p53 mutation and p21 expression in hepatocarcinogenesis induced by hepatitis B virus (HBV) and aflatoxin B1 (AFB1) in tree shrews, and to reveal the role of these genes in hepatocarcinogenesis.METHODS: Tree shrews were divided into four groups:group A, those infected with HBV and fed with AFB1 (n = 39);group B, those infected with HBV alone (n = 28); group C,those fed with AFB1 alone (n = 29); and group D, normal controls (n = 20). The tree shrews underwent liver biopsies once every 15 wk. Expression of p53 and p21 proteins and genes in the biopsies and tumor tissues of the experimental tree shrews was detected, respectively, by immunohistochemistry,and by Southem blotting and reverse transcription-polymerase chain reaction and sequencing.RESULTS: The incidence of hepatocellular carcinomas (HCC) was higher in group A (66.7%) than that in group B (3.57%) and C (30%). The time of HCC occurrence was also earlier in group A than that in group C (120.0±16.6 wk vs 153.3±5.8 wk, respectively, P<0.01). p53 protein was not detected by immunohistochemistry in all groups before the 75^th wk of the experiment. At the 105^th wk, the positive rates fo p53 were 78.6%, 60% and 71.4% in groups A, B and C, respectively, which were significantly higher than that in group D (10%) (all P<0.05). An abnormal band of p53 gene was observed in groups A and C. The mutation points of p53gene in tree shrews with HCC were at codons 275, 78 and 13. The nucleotide sequence and amino acid sequence of tree shrew's wild-type p53 showed 91.7% and 93.4% homologies with those of human p53,respectively. The immunopositivity for p21 was found before HCC development. The incidence of HCC was significantly higher in tree shrews that were positive for p21 than those negative for p21 (80.0% vs 11.0%, P<0.001).The incidence of HCC in p21 positive animals in group A was significantly higher than those positive for p21 in group C (P<O.05).CONCLUSION: A remarkable synergistic effect on HCC development exists between HBV and AFB1. p53 mutation promotes the development of HCC. HBV and AFB1 may synergistically induce p53 gene mutation, and stimulate ras gene expression, ras gene is activated at the earlier stage during hepatocarcinogenesis, p21 protein may be an early marker, and the alterations of p53 may be a late event in the development of HCC.展开更多
Background: Esophageal squamous cell carcinoma(ESCC) is a leading cause of cancer?related death, and new prognostic biomarkers are urgently needed. Apoptosis?stimulating P53?binding protein 1(ASPP1) and 2(ASPP2) have ...Background: Esophageal squamous cell carcinoma(ESCC) is a leading cause of cancer?related death, and new prognostic biomarkers are urgently needed. Apoptosis?stimulating P53?binding protein 1(ASPP1) and 2(ASPP2) have been reported to play important roles in the development, progression, metastasis, and prognosis of cancers, but their roles in ESCC have not been elucidated. In this study, we examined the expression of ASPP1 and ASPP2 in ESCC to evaluate their prognostic values.Methods: The protein expression of ASPP1, ASPP2, and P53 in 175 specimens of ESCC was detected using immuno?histochemical staining; their expression in cancerous and noncancerous tissues was scored according to the stain?ing intensity and the percentage of stained cells. The associations of ASPP1, ASPP2, and P53 with clinicopathologic parameters, overall survival(OS), and disease?free survival(DFS) were analyzed.Results: The protein expression levels of ASPP2 and P53 were significantly higher in cancerous tissues than in paired noncancerous tissues(P < 0.001), whereas the expression levels of ASPP1 in the two groups were similar. In ESCCs, ASPP1 expression was significantly associated with histological differentiation(P = 0.002) and invasive depth(P = 0.014); ASPP2 expression was associated with age(P = 0.029) and histological differentiation(P < 0.001); and P53 expression was associated with age(P and P53 expression. Survival an= 0.021) and tumor size(P alysis revealed that high AS= 0.040). No correlations were found between ASPP1, ASPP2,PP2 expression was significantly associated with increased 5?year OS(P = 0.001) and DFS rates(P ate of ESCC patients(= 0.010) and that high P53 expression was significantly associated with a reduced 5?year DFS rP atio(HR): 0.541, 9= 0.015). Multivariate Cox analysis indicated that ASPP2 was an inde?pendent predictor of OS [hazard r5% confidence interval(CI) 0.363–0.804] and DFS(HR: 0.599, 95% CI 0.404–0.888) of ESCC patients and that P53 was an independent predictor of DFS(HR: 2.161, 95% CI 1.100–4.245).Conclusions: ASPP1 might be involved in the progression of ESCC, and ASPP2 was a potential prognostic biomarker of ESCC and should be evaluated in future studies.展开更多
AIM To explore the effects of omeprazole on chemoradiotherapy efficacy and tumor recurrence in rectal cancer. METHODS The medical data of 125 rectal cancer patients who received the same neoadjuvant chemoradiotherapy(...AIM To explore the effects of omeprazole on chemoradiotherapy efficacy and tumor recurrence in rectal cancer. METHODS The medical data of 125 rectal cancer patients who received the same neoadjuvant chemoradiotherapy(CRT) followed by surgery were retrospectively collected. Patients who received omeprazole(OME) orally at a dose of 20 mg at least once daily for six days and/or intravenously at 40 mg a day were recognized as eligible OME users(EOU). Otherwise, patients were regarded as non-eligible OME users(non-EOU).Moreover, a preferred OME dose cut-off of 200 mg on tumor recurrence was obtained by receiver operating characteristic(ROC) curves. Patients were divided into two groups: the effective OME group(EOG, OME ≥ 200 mg) and the non-effective OME group(non-EOG, OME < 200 mg). RESULTS The good response rate of CRT efficacy(50.8%) in EOU was significantly increased compared with nonEOU(30.6%)(P = 0.02). The recurrence rate in the EOG was 10.3%, which was significantly lower compared with 31.3% in non-EOG(P = 0.025). The good response rate of CRT efficacy in EOG was 55.2%, which was obviously higher compared with 36.5% in non-EOG, with a significant difference(P = 0.072). Multivariate Cox analysis demonstrated that OME(nonEOG and EOG) was an independent and significant impact factor for DFS(P = 0.048, HR = 0.30, 95%CI: 0.09-0.99).CONCLUSION When applied as an adjuvant drug in cancer treatment for relieving common side effects of chemotherapy, omeprazole has a synergetic effect in improving CRT efficacy and decreasing rectal cancer recurrence.展开更多
AIM: To investigate the clinical significance of methylmethanesulfonate sensitivity 19(MMS19) expression in esophageal squamous cell carcinoma(ESCC).METHODS: Between June 2008 and May 2013, specimens from 103 patients...AIM: To investigate the clinical significance of methylmethanesulfonate sensitivity 19(MMS19) expression in esophageal squamous cell carcinoma(ESCC).METHODS: Between June 2008 and May 2013, specimens from 103 patients who underwent endoscopic biopsy for the diagnosis of ESCC at the endoscopy center of Sun Yat-Sen University Cancer Center were collected; 52 matched-normal esophageal squamous epithelium samples were biopsied as controls.MMS19 protein expression was measured by immunohistochemistry.Of the 103 cases of ESCC, 49 received radical surgery following neoadjuvant chemoradiotherapy consisting of concurrent radiation in a total dose of 40 Gy and two cycles of chemotherapy with vinorelbine and cisplatin.Relationships between MMS19 expression, clinicopathologic characteristics and chemoradiotherapy response were analyzed.RESULTS: The MMS19 protein could be detected in both the cytoplasm and nucleus of most specimens.High cytoplasmic expression of MMS19 was detected in 63.1% of ESCC samples, whereas high nuclearexpression of MMS19 was found in 35.0%.High cytoplasmic MMS19 expression was associated with regional lymph node metastases(OR = 11.3, 95%CI: 2.3-54.7; P < 0.001) and distant metastases(OR = 13.1, 95%CI: 1.7-103.0; P = 0.002).Furthermore, high cytoplasmic MMS19 expression was associated with a response of ESCC to chemoradiotherapy(OR = 11.5, 95%CI: 3.0-44.5; P < 0.001), with a high cytoplasmic MMS19 expression rates in 79.3% and 25.0% of patients from the good chemoradiotherapy response group and poor response group, respectively.Nuclear MMS19 expression did not show any significant association with clinicopathologic characteristics or chemoradiotherapy response in ESCC.CONCLUSION: The results of our preliminary study suggest that MMS19 may be a potential new predictor of metastasis and chemoradiotherapy response in ESCC.展开更多
AIMTo identify the disease-causing gene mutation in a Chinese pedigree with autosomal dominant cone-rod dystrophy (adCORD).METHODSA southern Chinese adCORD pedigree including 9 affected individuals was studied. Whole-...AIMTo identify the disease-causing gene mutation in a Chinese pedigree with autosomal dominant cone-rod dystrophy (adCORD).METHODSA southern Chinese adCORD pedigree including 9 affected individuals was studied. Whole-exome sequencing (WES), coupling the Agilent whole-exome capture system to the Illumina HiSeq 2000 DNA sequencing platform was used to search the specific gene mutation in 3 affected family members and 1 unaffected member. After a suggested variant was found through the data analysis, the putative mutation was validated by Sanger DNA sequencing of samples from all available family members.RESULTSThe results of both WES and Sanger sequencing revealed a novel nonsense mutation c.C766T (p.Q256X) within exon 5 of CRX gene which was pathogenic for adCORD in this family. The mutation could affect photoreceptor-specific gene expression with a dominant-negative effect and resulted in loss of the OTX tail, thus the mutant protein occupies the CRX-binding site in target promoters without establishing an interaction and, consequently, may block transactivation.CONCLUSIONAll modes of Mendelian inheritance in CORD have been observed, and genetic heterogeneity is a hallmark of CORD. Therefore, conventional genetic diagnosis of CORD would be time-consuming and labor-intensive. Our study indicated the robustness and cost-effectiveness of WES in the genetic diagnosis of CORD.展开更多
Hepatocellular carcinoma(HCC)is a common malignant tumor with high incidence and cancer mortality worldwide.Post-translational modifications(PTMs)of proteins have a great impact on protein function.Almost all proteins...Hepatocellular carcinoma(HCC)is a common malignant tumor with high incidence and cancer mortality worldwide.Post-translational modifications(PTMs)of proteins have a great impact on protein function.Almost all proteins can undergo PTMs,including phosphorylation,acetylation,methylation,glycosylation,ubiquitination,and so on.Many studies have shown that PTMs are related to the occurrence and development of cancers.The findings provide novel therapeutic targets for cancers,such as glypican-3 and mucin-1.Other clinical implications are also found in the studies of PTMs.Diagnostic or prognostic value,and response to therapy have been identified.In HCC,it has been shown that glycosylated alpha-fetoprotein(AFP)has a higher detection rate for early liver cancer than conventional AFP.In this review,we mainly focused on the diagnostic and prognostic value of PTM,in order to provide new insights into the clinical implication of PTM in HCC.展开更多
基金supported by the National Natural Science Foundation of China,Nos. 81771346, 82071383the Natural Science Foundation of Shandong Province (Key Project),No. ZR2020KH007+3 种基金the Taishan Scholar Youth Program of Shandong Province,No. tsqn201812156Academic Promotion Program of Shandong First Medical University,Nos. 2019QL025, 2019RC021Spring Industry Leader Talent Support Plan,No. 201984Rongxiang Regenerative Medicine Fund,No. 2019SDRX-23 (all to BN)。
文摘Studies have shown that gut microbiota metabolites can enter the central nervous system via the blood-spinal cord barrier and cause neuroinflammation, thus constituting secondary injury after spinal cord injury. To investigate the correlation between gut microbiota and metabolites and the possible mechanism underlying the effects of gut microbiota on secondary injury after spinal cord injury, in this study, we established mouse models of T8–T10 traumatic spinal cord injury. We used 16 S rRNA gene amplicon sequencing and metabolomics to reveal the changes in gut microbiota and metabolites in fecal samples from the mouse model. Results showed a severe gut microbiota disturbance after spinal cord injury, which included marked increases in pro-inflammatory bacteria, such as Shigella, Bacteroides, Rikenella, Staphylococcus, and Mucispirillum and decreases in anti-inflammatory bacteria, such as Lactobacillus, Allobaculum, and Sutterella. Meanwhile, we identified 27 metabolites that decreased and 320 metabolites that increased in the injured spinal cord. Combined with pathway enrichment analysis, five markedly differential amino acids(L-leucine, L-methionine, L-phenylalanine, L-isoleucine and L-valine) were screened out, which play a pivotal role in activating oxidative stress and inflammatory responses following spinal cord injury. Integrated correlation analysis indicated that the alteration of gut microbiota was related to the differences in amino acids, which suggests that disturbances in gut microbiota might participate in the secondary injury through the accumulation of partial metabolites that activate oxidative stress and inflammatory responses. Findings from this study provide a new theoretical basis for improving the secondary injury after spinal cord injury through fecal microbial transplantation.
基金Supported by the National Natural Science Foundation of China,No.39260033Natural Science Foundation of Guangxi,No.0143058
文摘AIM: To investigate p53 mutation and p21 expression in hepatocarcinogenesis induced by hepatitis B virus (HBV) and aflatoxin B1 (AFB1) in tree shrews, and to reveal the role of these genes in hepatocarcinogenesis.METHODS: Tree shrews were divided into four groups:group A, those infected with HBV and fed with AFB1 (n = 39);group B, those infected with HBV alone (n = 28); group C,those fed with AFB1 alone (n = 29); and group D, normal controls (n = 20). The tree shrews underwent liver biopsies once every 15 wk. Expression of p53 and p21 proteins and genes in the biopsies and tumor tissues of the experimental tree shrews was detected, respectively, by immunohistochemistry,and by Southem blotting and reverse transcription-polymerase chain reaction and sequencing.RESULTS: The incidence of hepatocellular carcinomas (HCC) was higher in group A (66.7%) than that in group B (3.57%) and C (30%). The time of HCC occurrence was also earlier in group A than that in group C (120.0±16.6 wk vs 153.3±5.8 wk, respectively, P<0.01). p53 protein was not detected by immunohistochemistry in all groups before the 75^th wk of the experiment. At the 105^th wk, the positive rates fo p53 were 78.6%, 60% and 71.4% in groups A, B and C, respectively, which were significantly higher than that in group D (10%) (all P<0.05). An abnormal band of p53 gene was observed in groups A and C. The mutation points of p53gene in tree shrews with HCC were at codons 275, 78 and 13. The nucleotide sequence and amino acid sequence of tree shrew's wild-type p53 showed 91.7% and 93.4% homologies with those of human p53,respectively. The immunopositivity for p21 was found before HCC development. The incidence of HCC was significantly higher in tree shrews that were positive for p21 than those negative for p21 (80.0% vs 11.0%, P<0.001).The incidence of HCC in p21 positive animals in group A was significantly higher than those positive for p21 in group C (P<O.05).CONCLUSION: A remarkable synergistic effect on HCC development exists between HBV and AFB1. p53 mutation promotes the development of HCC. HBV and AFB1 may synergistically induce p53 gene mutation, and stimulate ras gene expression, ras gene is activated at the earlier stage during hepatocarcinogenesis, p21 protein may be an early marker, and the alterations of p53 may be a late event in the development of HCC.
基金supported by grants from the Research Fund of Guangdong Esophageal Cancer Institute of China(Grant No:M201412 for H-YW)the Research Fund of the State Key Laboratory of Oncology in South China(to H-YW)
文摘Background: Esophageal squamous cell carcinoma(ESCC) is a leading cause of cancer?related death, and new prognostic biomarkers are urgently needed. Apoptosis?stimulating P53?binding protein 1(ASPP1) and 2(ASPP2) have been reported to play important roles in the development, progression, metastasis, and prognosis of cancers, but their roles in ESCC have not been elucidated. In this study, we examined the expression of ASPP1 and ASPP2 in ESCC to evaluate their prognostic values.Methods: The protein expression of ASPP1, ASPP2, and P53 in 175 specimens of ESCC was detected using immuno?histochemical staining; their expression in cancerous and noncancerous tissues was scored according to the stain?ing intensity and the percentage of stained cells. The associations of ASPP1, ASPP2, and P53 with clinicopathologic parameters, overall survival(OS), and disease?free survival(DFS) were analyzed.Results: The protein expression levels of ASPP2 and P53 were significantly higher in cancerous tissues than in paired noncancerous tissues(P < 0.001), whereas the expression levels of ASPP1 in the two groups were similar. In ESCCs, ASPP1 expression was significantly associated with histological differentiation(P = 0.002) and invasive depth(P = 0.014); ASPP2 expression was associated with age(P = 0.029) and histological differentiation(P < 0.001); and P53 expression was associated with age(P and P53 expression. Survival an= 0.021) and tumor size(P alysis revealed that high AS= 0.040). No correlations were found between ASPP1, ASPP2,PP2 expression was significantly associated with increased 5?year OS(P = 0.001) and DFS rates(P ate of ESCC patients(= 0.010) and that high P53 expression was significantly associated with a reduced 5?year DFS rP atio(HR): 0.541, 9= 0.015). Multivariate Cox analysis indicated that ASPP2 was an inde?pendent predictor of OS [hazard r5% confidence interval(CI) 0.363–0.804] and DFS(HR: 0.599, 95% CI 0.404–0.888) of ESCC patients and that P53 was an independent predictor of DFS(HR: 2.161, 95% CI 1.100–4.245).Conclusions: ASPP1 might be involved in the progression of ESCC, and ASPP2 was a potential prognostic biomarker of ESCC and should be evaluated in future studies.
文摘AIM To explore the effects of omeprazole on chemoradiotherapy efficacy and tumor recurrence in rectal cancer. METHODS The medical data of 125 rectal cancer patients who received the same neoadjuvant chemoradiotherapy(CRT) followed by surgery were retrospectively collected. Patients who received omeprazole(OME) orally at a dose of 20 mg at least once daily for six days and/or intravenously at 40 mg a day were recognized as eligible OME users(EOU). Otherwise, patients were regarded as non-eligible OME users(non-EOU).Moreover, a preferred OME dose cut-off of 200 mg on tumor recurrence was obtained by receiver operating characteristic(ROC) curves. Patients were divided into two groups: the effective OME group(EOG, OME ≥ 200 mg) and the non-effective OME group(non-EOG, OME < 200 mg). RESULTS The good response rate of CRT efficacy(50.8%) in EOU was significantly increased compared with nonEOU(30.6%)(P = 0.02). The recurrence rate in the EOG was 10.3%, which was significantly lower compared with 31.3% in non-EOG(P = 0.025). The good response rate of CRT efficacy in EOG was 55.2%, which was obviously higher compared with 36.5% in non-EOG, with a significant difference(P = 0.072). Multivariate Cox analysis demonstrated that OME(nonEOG and EOG) was an independent and significant impact factor for DFS(P = 0.048, HR = 0.30, 95%CI: 0.09-0.99).CONCLUSION When applied as an adjuvant drug in cancer treatment for relieving common side effects of chemotherapy, omeprazole has a synergetic effect in improving CRT efficacy and decreasing rectal cancer recurrence.
文摘AIM: To investigate the clinical significance of methylmethanesulfonate sensitivity 19(MMS19) expression in esophageal squamous cell carcinoma(ESCC).METHODS: Between June 2008 and May 2013, specimens from 103 patients who underwent endoscopic biopsy for the diagnosis of ESCC at the endoscopy center of Sun Yat-Sen University Cancer Center were collected; 52 matched-normal esophageal squamous epithelium samples were biopsied as controls.MMS19 protein expression was measured by immunohistochemistry.Of the 103 cases of ESCC, 49 received radical surgery following neoadjuvant chemoradiotherapy consisting of concurrent radiation in a total dose of 40 Gy and two cycles of chemotherapy with vinorelbine and cisplatin.Relationships between MMS19 expression, clinicopathologic characteristics and chemoradiotherapy response were analyzed.RESULTS: The MMS19 protein could be detected in both the cytoplasm and nucleus of most specimens.High cytoplasmic expression of MMS19 was detected in 63.1% of ESCC samples, whereas high nuclearexpression of MMS19 was found in 35.0%.High cytoplasmic MMS19 expression was associated with regional lymph node metastases(OR = 11.3, 95%CI: 2.3-54.7; P < 0.001) and distant metastases(OR = 13.1, 95%CI: 1.7-103.0; P = 0.002).Furthermore, high cytoplasmic MMS19 expression was associated with a response of ESCC to chemoradiotherapy(OR = 11.5, 95%CI: 3.0-44.5; P < 0.001), with a high cytoplasmic MMS19 expression rates in 79.3% and 25.0% of patients from the good chemoradiotherapy response group and poor response group, respectively.Nuclear MMS19 expression did not show any significant association with clinicopathologic characteristics or chemoradiotherapy response in ESCC.CONCLUSION: The results of our preliminary study suggest that MMS19 may be a potential new predictor of metastasis and chemoradiotherapy response in ESCC.
基金Supported by the Zhejiang Provincial Natural Science Foundation of China (No.LY12H12001)the Ningbo Key Foundation of Society Development (No.2014C50091)+2 种基金the Ningbo Natural Science Foundation (No.2012A610192)the Ningbo Yinzhou District S&T Foundation (No.YK2013-90)the Shenzhen Municipal Government of China (No.GJHZ20130417140916986)
文摘AIMTo identify the disease-causing gene mutation in a Chinese pedigree with autosomal dominant cone-rod dystrophy (adCORD).METHODSA southern Chinese adCORD pedigree including 9 affected individuals was studied. Whole-exome sequencing (WES), coupling the Agilent whole-exome capture system to the Illumina HiSeq 2000 DNA sequencing platform was used to search the specific gene mutation in 3 affected family members and 1 unaffected member. After a suggested variant was found through the data analysis, the putative mutation was validated by Sanger DNA sequencing of samples from all available family members.RESULTSThe results of both WES and Sanger sequencing revealed a novel nonsense mutation c.C766T (p.Q256X) within exon 5 of CRX gene which was pathogenic for adCORD in this family. The mutation could affect photoreceptor-specific gene expression with a dominant-negative effect and resulted in loss of the OTX tail, thus the mutant protein occupies the CRX-binding site in target promoters without establishing an interaction and, consequently, may block transactivation.CONCLUSIONAll modes of Mendelian inheritance in CORD have been observed, and genetic heterogeneity is a hallmark of CORD. Therefore, conventional genetic diagnosis of CORD would be time-consuming and labor-intensive. Our study indicated the robustness and cost-effectiveness of WES in the genetic diagnosis of CORD.
基金funded by National Natural Science Foundation of China(81772982)the Special Innovation Fund of Department of Education of Guangdong Province(2019KTSCX049)+1 种基金Discipline Construction Project of Guang-dong Medical University(4SG23034G)Talent Development Foundation of The First Dongguan Affiliated Hospital of Guangdong Medical University(PF100-2-03).
文摘Hepatocellular carcinoma(HCC)is a common malignant tumor with high incidence and cancer mortality worldwide.Post-translational modifications(PTMs)of proteins have a great impact on protein function.Almost all proteins can undergo PTMs,including phosphorylation,acetylation,methylation,glycosylation,ubiquitination,and so on.Many studies have shown that PTMs are related to the occurrence and development of cancers.The findings provide novel therapeutic targets for cancers,such as glypican-3 and mucin-1.Other clinical implications are also found in the studies of PTMs.Diagnostic or prognostic value,and response to therapy have been identified.In HCC,it has been shown that glycosylated alpha-fetoprotein(AFP)has a higher detection rate for early liver cancer than conventional AFP.In this review,we mainly focused on the diagnostic and prognostic value of PTM,in order to provide new insights into the clinical implication of PTM in HCC.
