Genetic variants in super-enhancers(SEs)are increasingly implicated as a disease risk-driving mechanism.Previous studies have reported an associations between benzo[a]pyrene(BaP)exposure and some malignant tumor risk....Genetic variants in super-enhancers(SEs)are increasingly implicated as a disease risk-driving mechanism.Previous studies have reported an associations between benzo[a]pyrene(BaP)exposure and some malignant tumor risk.Currently,it is unclear whether BaP is involved in the effect of genetic variants in SEs on prostate cancer risk,nor the associated intrinsic molecular mechanisms.In the current study,by using logistic regression analysis,we found that rs5750581T>C in 22q-SE was significantly associated with prostate cancer risk(odds ratio=1.26,P=7.61×10^(-5)).We also have found that the rs6001092T>G,in a high linkage disequilibrium with rs5750581T>C(r^(2)=0.98),is located in a regulatory aryl hydrocarbon receptor(AhR)motif and may interact with the FAM227A promoter in further bioinformatics analysis.We then performed a series of functional and BaP acute exposure experiments to assess biological function of the genetic variant and the target gene.Biologically,the rs6001092-G allele strengthened the transcription factor binding affinity to AhR,thereby upregulating FAM227A,especially upon exposure to BaP,which induced the malignant phenotypes of prostate cancer.The current study highlights that AhR acts as an environmental sensor of BaP and is involved in the SE-mediated prostate cancer risk,which may provide new insights into the etiology of prostate cancer associated with the inherited SE variants under environmental carcinogen stressors.展开更多
The interplay between DNA replication stress and immune microenvironment alterations is known to play a crucial role in colorectal tumorigenesis,but a comprehensive understanding of their association with and relevant...The interplay between DNA replication stress and immune microenvironment alterations is known to play a crucial role in colorectal tumorigenesis,but a comprehensive understanding of their association with and relevant biomarkers involved in colorectal tumorigenesis is lacking.To address this gap,we conducted a study aiming to investigate this association and identify relevant biomarkers.We analyzed transcriptomic and proteomic profiles of 904 colorectal tumor tissues and 342 normal tissues to examine pathway enrichment,biological activity,and the immune microenvironment.Additionally,we evaluated genetic effects of single variants and genes on colorectal cancer susceptibility using data from genome-wide association studies(GWASs)involving both East Asian(7062 cases and 195745 controls)and European(24476 cases and 23073 controls)populations.We employed mediation analysis to infer the causal pathway,and applied multiplex immunofluorescence to visualize colocalized biomarkers in colorectal tumors and immune cells.Our findings revealed that both DNA replication activity and the flap structure-specific endonuclease 1(FEN1)gene were significantly enriched in colorectal tumor tissues,compared with normal tissues.Moreover,a genetic variant rs4246215 G>T in FEN1 was associated with a decreased risk of colorectal cancer(odds ratio=0.94,95%confidence interval:0.90–0.97,P_(meta)=4.70×10^(-9)).Importantly,we identified basophils and eosinophils that both exhibited a significantly decreased infiltration in colorectal tumors,and were regulated by rs4246215 through causal pathways involving both FEN1 and DNA replication.In conclusion,this trans-omics incorporating GWAS data provides insights into a plausible pathway connecting DNA replication and immunity,expanding biological knowledge of colorectal tumorigenesis and therapeutic targets.展开更多
Objective To assess the feasibility of internal suspension technique in retroperitoneal robot-assisted laparoscopic partial nephrectomy(rRAPN)with a new robotic platform called KangDuo Surgical Robot-01(KD-SR-01)syste...Objective To assess the feasibility of internal suspension technique in retroperitoneal robot-assisted laparoscopic partial nephrectomy(rRAPN)with a new robotic platform called KangDuo Surgical Robot-01(KD-SR-01)system(Suzhou KangDuo Robot Co.,Ltd.,Suzhou,China)and discuss its surgical technique.Methods A 44-year-old male patient was admitted with a 2.5 cm tumor on dorsolateral upper pole of the left kidney.The R.E.N.A.L.nephrometry score of this patient was 4x.This patient underwent rRAPN with KD-SR-01.The perinephric fat between the tumor and Gerota's fascia was preserved,which was used for internal suspension traction during tumor resection.Postoperative follow-up data were collected.Results The surgery was successfully carried out with a duration of 127 min,in which the docking time was 6 min 25 s and console time was 60 min.The warm ischemia time was 19 min 53 s,and the estimated blood loss was 0 mL.The pathological histology showed a pathological tumor stage 1a clear cell renal cell carcinoma,with a negative surgical margin.The World Health Organization/International Society of Urological Pathology(WHO/ISUP)grade of this patient was Grade 2.No recurrence was observed during the 6-month follow-up.Conclusion Internal suspension in rRAPN is feasible and effective with use of the new robotic system KD-SR-01.展开更多
文摘Genetic variants in super-enhancers(SEs)are increasingly implicated as a disease risk-driving mechanism.Previous studies have reported an associations between benzo[a]pyrene(BaP)exposure and some malignant tumor risk.Currently,it is unclear whether BaP is involved in the effect of genetic variants in SEs on prostate cancer risk,nor the associated intrinsic molecular mechanisms.In the current study,by using logistic regression analysis,we found that rs5750581T>C in 22q-SE was significantly associated with prostate cancer risk(odds ratio=1.26,P=7.61×10^(-5)).We also have found that the rs6001092T>G,in a high linkage disequilibrium with rs5750581T>C(r^(2)=0.98),is located in a regulatory aryl hydrocarbon receptor(AhR)motif and may interact with the FAM227A promoter in further bioinformatics analysis.We then performed a series of functional and BaP acute exposure experiments to assess biological function of the genetic variant and the target gene.Biologically,the rs6001092-G allele strengthened the transcription factor binding affinity to AhR,thereby upregulating FAM227A,especially upon exposure to BaP,which induced the malignant phenotypes of prostate cancer.The current study highlights that AhR acts as an environmental sensor of BaP and is involved in the SE-mediated prostate cancer risk,which may provide new insights into the etiology of prostate cancer associated with the inherited SE variants under environmental carcinogen stressors.
基金supported by the National Natural Science Foundation of China(Grant No.82173601)Yili&Jiangsu Joint Institute of Health(Grant No.yl2021ms02).
文摘The interplay between DNA replication stress and immune microenvironment alterations is known to play a crucial role in colorectal tumorigenesis,but a comprehensive understanding of their association with and relevant biomarkers involved in colorectal tumorigenesis is lacking.To address this gap,we conducted a study aiming to investigate this association and identify relevant biomarkers.We analyzed transcriptomic and proteomic profiles of 904 colorectal tumor tissues and 342 normal tissues to examine pathway enrichment,biological activity,and the immune microenvironment.Additionally,we evaluated genetic effects of single variants and genes on colorectal cancer susceptibility using data from genome-wide association studies(GWASs)involving both East Asian(7062 cases and 195745 controls)and European(24476 cases and 23073 controls)populations.We employed mediation analysis to infer the causal pathway,and applied multiplex immunofluorescence to visualize colocalized biomarkers in colorectal tumors and immune cells.Our findings revealed that both DNA replication activity and the flap structure-specific endonuclease 1(FEN1)gene were significantly enriched in colorectal tumor tissues,compared with normal tissues.Moreover,a genetic variant rs4246215 G>T in FEN1 was associated with a decreased risk of colorectal cancer(odds ratio=0.94,95%confidence interval:0.90–0.97,P_(meta)=4.70×10^(-9)).Importantly,we identified basophils and eosinophils that both exhibited a significantly decreased infiltration in colorectal tumors,and were regulated by rs4246215 through causal pathways involving both FEN1 and DNA replication.In conclusion,this trans-omics incorporating GWAS data provides insights into a plausible pathway connecting DNA replication and immunity,expanding biological knowledge of colorectal tumorigenesis and therapeutic targets.
文摘Objective To assess the feasibility of internal suspension technique in retroperitoneal robot-assisted laparoscopic partial nephrectomy(rRAPN)with a new robotic platform called KangDuo Surgical Robot-01(KD-SR-01)system(Suzhou KangDuo Robot Co.,Ltd.,Suzhou,China)and discuss its surgical technique.Methods A 44-year-old male patient was admitted with a 2.5 cm tumor on dorsolateral upper pole of the left kidney.The R.E.N.A.L.nephrometry score of this patient was 4x.This patient underwent rRAPN with KD-SR-01.The perinephric fat between the tumor and Gerota's fascia was preserved,which was used for internal suspension traction during tumor resection.Postoperative follow-up data were collected.Results The surgery was successfully carried out with a duration of 127 min,in which the docking time was 6 min 25 s and console time was 60 min.The warm ischemia time was 19 min 53 s,and the estimated blood loss was 0 mL.The pathological histology showed a pathological tumor stage 1a clear cell renal cell carcinoma,with a negative surgical margin.The World Health Organization/International Society of Urological Pathology(WHO/ISUP)grade of this patient was Grade 2.No recurrence was observed during the 6-month follow-up.Conclusion Internal suspension in rRAPN is feasible and effective with use of the new robotic system KD-SR-01.
