Esophageal squamous-cell carcinoma （ESCC） is one of the most lethal malignancies in the world and occurs at particularly higher frequency in China. While several genome-wide association studies （GWAS） of germline ...Esophageal squamous-cell carcinoma （ESCC） is one of the most lethal malignancies in the world and occurs at particularly higher frequency in China. While several genome-wide association studies （GWAS） of germline variants and whole-genome or whole-exome sequencing studies of somatic mutations in ESCC have been published, there is no comprehensive database publically available for this cancer. Here, we developed the Chinese Cancer Genomic Database-Esophageal Squamous Cell Carcinoma （CCGD-ESCC） database, which contains the associations of 69,593 single nucleotide polymorphisms （SNPs） with ESCC risk in 2022 cases and 2039 controls, survival time of 1006 ESCC patients （survival GWAS） and gene expression （expression quantitative trait loci,eQTL） in 94 ESCC patients. Moreover, this database also provides the associations between8833 somatic mutations and survival time in 675 ESCC patients. Our user-friendly database is a resource useful for biologists and oncologists not only in identifying the associations of genetic variants or somatic mutations with the development and progression of ESCC but also in studying the underlying mechanisms for tumorigenesis of the cancer. CCGD-ESCC is freely accessible at http：//db.cbi.pku.edu.cn/ccgd/ESCCdb.展开更多
Dear Editor,Esophageal squamous cell carcinoma(ESCC)has poor prognosis because of the difficulty in early detection and low sensitivity of advanced disease to radiochemotherapy.1,2 ESCC presents a high proportion of p...Dear Editor,Esophageal squamous cell carcinoma(ESCC)has poor prognosis because of the difficulty in early detection and low sensitivity of advanced disease to radiochemotherapy.1,2 ESCC presents a high proportion of primary resistance to radiochemotherapy,2which may be due to certain individual genetic variations.Expression quantitative trait loci(eQTLs)as proximal and continuous cellular phenotypes have been shown to be helpful to determine how genetic variants may influence phenotype.展开更多
Background:Pancreatic duct adenocarcinoma(PDAC)remains a major health problem because conventional can-cer treatments are relatively ineffective against it.Microarray studies have linked many genes to pancreatic cance...Background:Pancreatic duct adenocarcinoma(PDAC)remains a major health problem because conventional can-cer treatments are relatively ineffective against it.Microarray studies have linked many genes to pancreatic cancer,but the available data have not been extensively mined for potential insights into PDAC.This study attempted to identify PDAC-associated genes and signaling pathways based on six microarray-based profiles of gene expression in pancre-atic cancer deposited in the gene expression omnibus database.Methods:Pathway network methods were used to analyze core pathways in six publicly available pancreatic cancer gene(GSE71989,GSE15471,GSE16515,GSE32676,GSE41368 and GSE28735)expression profiles.Genes potentially linked to PDAC were assessed for potential impact on survival time based on data in The Cancer Genome Atlas and International Cancer Genome Consortium databases,and the expression of one candidate gene(CKS2)and its association with survival was examined in 102 patients with PDAC from our hospital.Effects of CKS2 knockdown were explored in the PDAC cell lines BxPC-3 and CFPAC-1.Results:The KEGG signaling pathway called“pathway in cancer”may play an important role in pancreatic cancer development and progression.Five genes(BIRC5,CKS2,ITGA3,ITGA6 and RALA)in this pathway were significantly associated with survival time in patients with PDAC.CKS2 was overexpressed in PDAC samples from our hospital,and higher CKS2 expression in these patients was associated with shorter survival time.CKS2 knockdown substantially inhibited PDAC cell proliferation in vitro.Conclusions:Analysis integrating existing microarray datasets allowed identification of the“pathway in cancer”as an important signaling pathway in PDAC.This integrative approach may be powerful for identifying genes and pathways involved in cancer.展开更多
基金supported by CAMS Innovation Fund for Medical Sciences (Grant No. 2016-I2M-4-002 awarded to CW)the National Key R&D Program (Grant No. 2016YFC1302701 to CW and Grant No. 2016YFC0901603 to GG)
文摘Esophageal squamous-cell carcinoma （ESCC） is one of the most lethal malignancies in the world and occurs at particularly higher frequency in China. While several genome-wide association studies （GWAS） of germline variants and whole-genome or whole-exome sequencing studies of somatic mutations in ESCC have been published, there is no comprehensive database publically available for this cancer. Here, we developed the Chinese Cancer Genomic Database-Esophageal Squamous Cell Carcinoma （CCGD-ESCC） database, which contains the associations of 69,593 single nucleotide polymorphisms （SNPs） with ESCC risk in 2022 cases and 2039 controls, survival time of 1006 ESCC patients （survival GWAS） and gene expression （expression quantitative trait loci,eQTL） in 94 ESCC patients. Moreover, this database also provides the associations between8833 somatic mutations and survival time in 675 ESCC patients. Our user-friendly database is a resource useful for biologists and oncologists not only in identifying the associations of genetic variants or somatic mutations with the development and progression of ESCC but also in studying the underlying mechanisms for tumorigenesis of the cancer. CCGD-ESCC is freely accessible at http：//db.cbi.pku.edu.cn/ccgd/ESCCdb.
基金This study was funded by National Science Fund for Distinguished Young Scholars(81725015 to CW)Chinese Academy Medical Sciences Innovation Fund for Medical Sciences(2021-2M-1-013)+1 种基金Beijing Outstanding Young Scientist Program(BJJWZYJH01201910023027 to C.W.)National Natural Science Foundation of China(81988101 to D.L.and C.W.).
文摘Dear Editor,Esophageal squamous cell carcinoma(ESCC)has poor prognosis because of the difficulty in early detection and low sensitivity of advanced disease to radiochemotherapy.1,2 ESCC presents a high proportion of primary resistance to radiochemotherapy,2which may be due to certain individual genetic variations.Expression quantitative trait loci(eQTLs)as proximal and continuous cellular phenotypes have been shown to be helpful to determine how genetic variants may influence phenotype.
基金supported by the National Natural Science Foundation of China(No.81572793,81772586 and 81602461)a Grant(No.2016A030313283)from the Natural Science Foundation of Guangdong Provincethe Peking Union Medical College Doctor Innovation Fund(No.2015-0710-17).
文摘Background:Pancreatic duct adenocarcinoma(PDAC)remains a major health problem because conventional can-cer treatments are relatively ineffective against it.Microarray studies have linked many genes to pancreatic cancer,but the available data have not been extensively mined for potential insights into PDAC.This study attempted to identify PDAC-associated genes and signaling pathways based on six microarray-based profiles of gene expression in pancre-atic cancer deposited in the gene expression omnibus database.Methods:Pathway network methods were used to analyze core pathways in six publicly available pancreatic cancer gene(GSE71989,GSE15471,GSE16515,GSE32676,GSE41368 and GSE28735)expression profiles.Genes potentially linked to PDAC were assessed for potential impact on survival time based on data in The Cancer Genome Atlas and International Cancer Genome Consortium databases,and the expression of one candidate gene(CKS2)and its association with survival was examined in 102 patients with PDAC from our hospital.Effects of CKS2 knockdown were explored in the PDAC cell lines BxPC-3 and CFPAC-1.Results:The KEGG signaling pathway called“pathway in cancer”may play an important role in pancreatic cancer development and progression.Five genes(BIRC5,CKS2,ITGA3,ITGA6 and RALA)in this pathway were significantly associated with survival time in patients with PDAC.CKS2 was overexpressed in PDAC samples from our hospital,and higher CKS2 expression in these patients was associated with shorter survival time.CKS2 knockdown substantially inhibited PDAC cell proliferation in vitro.Conclusions:Analysis integrating existing microarray datasets allowed identification of the“pathway in cancer”as an important signaling pathway in PDAC.This integrative approach may be powerful for identifying genes and pathways involved in cancer.
