Dataset Information

Genome-wide identification of cancer/testis genes and their association with prognosis in a pan-cancer analysis.

ABSTRACT: Cancer/testis (CT) genes are excellent candidates for cancer immunotherapies because of their restrict expression in normal tissues and the capacity to elicit an immune response when expressed in tumor cells. In this study, we provide a genome-wide screen for CT genes with the identification of 745 putative CT genes. Comparison with a set of known CT genes shows that 201 new CT genes were identified. Integration of gene expression and clinical data led us to identify dozens of CT genes associated with either good or poor prognosis. For the CT genes related to good prognosis, we show that there is a direct relationship between CT gene expression and a signal for CD8+ cells infiltration for some tumor types, especially melanoma.

SUBMITTER: da Silva VL

PROVIDER: S-EPMC5696236 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

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Genome-wide identification of cancer/testis genes and their association with prognosis in a pan-cancer analysis.

da Silva Vandeclecio Lira VL Fonseca André Faustino AF Fonseca Marbella M da Silva Thayna Emilia TE Coelho Ana Carolina AC Kroll José Eduardo JE de Souza Jorge Estefano Santana JES Stransky Beatriz B de Souza Gustavo Antonio GA de Souza Sandro José SJ

Oncotarget 20171010 54

Cancer/testis (CT) genes are excellent candidates for cancer immunotherapies because of their restrict expression in normal tissues and the capacity to elicit an immune response when expressed in tumor cells. In this study, we provide a genome-wide screen for CT genes with the identification of 745 putative CT genes. Comparison with a set of known CT genes shows that 201 new CT genes were identified. Integration of gene expression and clinical data led us to identify dozens of CT genes associate ...[more]

PMID: 29190970

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Project description:ObjectiveGenome wide association studies (GWAs) of breast cancer mortality have identified few potential associations. The concordance between these studies is unclear. In this study, we used a meta-analysis of two prognostic GWAs and a replication cohort to identify the strongest associations and to evaluate the loci suggested in previous studies. We attempt to identify those SNPs which could impact overall survival irrespective of the age of onset.MethodsTo facilitate the meta-analysis and to refine the association signals, SNPs were imputed using data from the 1000 genomes project. Cox-proportional hazard models were used to estimate hazard ratios (HR) in 536 patients from the POSH cohort (Prospective study of Outcomes in Sporadic versus Hereditary breast cancer) and 805 patients from the HEBCS cohort (Helsinki Breast Cancer Study). These hazard ratios were combined using a Mantel-Haenszel fixed effects meta-analysis and a p-value threshold of 5×10(-8) was used to determine significance. Replication was performed in 1523 additional patients from the POSH study.ResultsAlthough no SNPs achieved genome wide significance, three SNPs have significant association in the replication cohort and combined p-values less than 5.6×10(-6). These SNPs are; rs421379 which is 556 kb upstream of ARRDC3 (HR?=?1.49, 95% confidence interval (CI)?=?1.27-1.75, P?=?1.1×10(-6)), rs12358475 which is between ECHDC3 and PROSER2 (HR?=?0.75, CI?=?0.67-0.85, P?=?1.8×10(-6)), and rs1728400 which is between LINC00917 and FOXF1.ConclusionsIn a genome wide meta-analysis of two independent cohorts from UK and Finland, we identified potential associations at three distinct loci. Phenotypic heterogeneity and relatively small sample sizes may explain the lack of genome wide significant findings. However, the replication at three SNPs in the validation cohort shows promise for future studies in larger cohorts. We did not find strong evidence for concordance between the few associations highlighted by previous GWAs of breast cancer survival and this study.

Dataset Information

Genome-wide identification of cancer/testis genes and their association with prognosis in a pan-cancer analysis.

Publications

Genome-wide identification of cancer/testis genes and their association with prognosis in a pan-cancer analysis.

Similar Datasets

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