Dataset Information

Observed Survival Interval: A Supplement to TCGA Pan-Cancer Clinical Data Resource.

ABSTRACT: To drive high-quality omics translational research using The Cancer Genome Atlas (TCGA) data, a TCGA Pan-Cancer Clinical Data Resource was proposed. However, there is an out-of-step issue between clinical outcomes and the omics data of TCGA for skin cutaneous melanoma (SKCM), due to the majority of metastatic samples. In clinical cases, the survival time started from the initial SKCM diagnosis, while the omics data were characterized at TCGA sampling. This study aimed to address this issue by proposing an observed survival interval (OBS), which was defined as the time interval from TCGA sampling to patient death or last follow-up. We compared the OBS with the usual recommended overall survival (OS) by associating them with both clinical data and microRNA sequencing data of TCGA-SKCM. We found that the OS of primary SKCM was significantly shorter than that of metastatic SKCM, while the opposite happened if OBS was compared. OS was associated with the pathological stage of both primary and metastatic SKCM, while OBS was associated with the pathological stage of primary SKCM but not that of metastatic SKCM. Five previously cross-validated survival-associated microRNAs were found to be associated with the OBS rather than OS in metastatic SKCM. Thus, the OBS was more appropriate for associating microRNA-omics data of TCGA-SKCM than OS, and it is a timely supplement to TCGA Pan-Cancer Clinical Data Resource.

SUBMITTER: Xiong J

PROVIDER: S-EPMC6468755 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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Observed Survival Interval: A Supplement to TCGA Pan-Cancer Clinical Data Resource.

Xiong Jie J Bing Zhitong Z Guo Shengyu S

Cancers 20190226 3

To drive high-quality omics translational research using The Cancer Genome Atlas (TCGA) data, a TCGA Pan-Cancer Clinical Data Resource was proposed. However, there is an out-of-step issue between clinical outcomes and the omics data of TCGA for skin cutaneous melanoma (SKCM), due to the majority of metastatic samples. In clinical cases, the survival time started from the initial SKCM diagnosis, while the omics data were characterized at TCGA sampling. This study aimed to address this issue by pr ...[more]

PMID: 30813652

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Project description:BACKGROUND:Ovarian cancer remains a significant public health burden, with the highest mortality rate of all the gynecological cancers. This is attributable to the late stage at which the majority of ovarian cancers are diagnosed, coupled with the low and variable response of advanced tumors to standard chemotherapies. To date, clinically useful predictors of treatment response remain lacking. Identifying the genetic determinants of ovarian cancer survival and treatment response is crucial to the development of prognostic biomarkers and personalized therapies that may improve outcomes for the late-stage patients who comprise the majority of cases. METHODS:To identify constitutional genetic variations contributing to ovarian cancer mortality, we systematically investigated associations between germline polymorphisms and ovarian cancer survival using data from The Cancer Genome Atlas Project (TCGA). Using stage-stratified Cox proportional hazards regression, we examined >650,000 SNP loci for association with survival. We additionally examined whether the association of significant SNPs with survival was modified by somatic alterations. RESULTS:Germline polymorphisms at rs4934282 (AGAP11/C10orf116) and rs1857623 (DNAH14) were associated with stage-adjusted survival (p= 1.12e-07 and 1.80e-07, FDR q= 1.2e-04 and 2.4e-04, respectively). A third SNP, rs4869 (C10orf116), was additionally identified as significant in the exome sequencing data; it is in near-perfect LD with rs4934282. The associations with survival remained significant when somatic alterations. CONCLUSIONS:Discovery analysis of TCGA data reveals germline genetic variations that may play a role in ovarian cancer survival even among late-stage cases. The significant loci are located near genes previously reported as having a possible relationship to platinum and taxol response. Because the variant alleles at the significant loci are common (frequencies for rs4934282 A/C alleles = 0.54/0.46, respectively; rs1857623 A/G alleles = 0.55/0.45, respectively) and germline variants can be assayed noninvasively, our findings provide potential targets for further exploration as prognostic biomarkers and individualized therapies.

Dataset Information

Observed Survival Interval: A Supplement to TCGA Pan-Cancer Clinical Data Resource.

Publications

Observed Survival Interval: A Supplement to TCGA Pan-Cancer Clinical Data Resource.

Similar Datasets

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