An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

Liu, Jianfang; Lichtenberg, Tara M.; Hoadley, Katherine A.; Poisson, Laila; Lazar, Alexander J.; Cherniack, Andrew D.; Kovatich, Albert J.; Benz, Christopher C.; Levine, Douglas A.; Lee, Adrian V.; Omberg, Larsson; Wolf, Denise M.; Shriver, Craig D.; Thórsson, Vésteinn; Hu, Hai

doi:10.1016/j.cell.2018.02.052

Cited by 2,292 publications

(1,855 citation statements)

References 49 publications

(82 reference statements)

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“…TCGA bam files used in the analyses were downloaded from the Genomic Data Commons Data Portal (https://portal.gdc.cancer.gov). Clinical and survival data of TCGA samples were retrieved from Reference . Genetic variability data of ABC transporters in the general population were retrieved from the Genome Aggregation Database (http://gnomad.broadinstitute.org/).…”

Section: Methodsmentioning

confidence: 99%

Germline variant burden in multidrug resistance transporters is a therapy‐specific predictor of survival in breast cancer patients

Xiao

Zhou

Winter

et al. 2020

Intl Journal of Cancer

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Multidrug resistance due to facilitated drug efflux mediated by ATP‐binding cassette (ABC) transporters is a main cause for failure of cancer therapy. Genetic polymorphisms in ABC genes affect the disposition of chemotherapeutics and constitute important biomarkers for therapeutic response and toxicity. Here we correlated germline variability in ABC transporters with disease‐specific survival (DSS) in 960 breast cancer (BRCA), 314 clear cell renal cell carcinoma and 325 hepatocellular carcinoma patients. We find that variant burden in ABCC1 is a strong predictor of DSS in BRCA patients, whereas candidate polymorphisms are not associated with DSS. This association is highly drug‐specific for subgroups treated with the MRP1 substrates cyclophosphamide (log‐rank p = 0.0011) and doxorubicin (log‐rank p = 0.0088) independent of age and tumor stage, whereas no association was found in individuals treated with tamoxifen (log‐rank p = 0.13). Structural mapping of significant variants revealed multiple variants at residues involved in protein stability, cofactor stabilization or substrate binding. Our results demonstrate that BRCA patients with high variant burden in ABCC1 are less prone to respond appropriately to pharmacological therapy with MRP1 substrates, thus incentivizing the consideration of genomic germline data for precision cancer medicine.

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Section: Methodsmentioning

confidence: 99%

Germline variant burden in multidrug resistance transporters is a therapy‐specific predictor of survival in breast cancer patients

Xiao

Zhou

Winter

et al. 2020

Intl Journal of Cancer

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“…For the first time, we assessed the expression of PP2A endogenous inhibitors (Table ) in two mesothelioma patient data sets: the Gordon data set from NCBI Gene Expression Omnibus database (Gordon et al, ), which contains five samples of normal pleura and 40 samples of mesothelioma tumor samples, and The Cancer Genome Atlas (TCGA) data set with 87 mesothelioma tumor samples (Liu et al, ). At first, we found that ARPP19, ANP32E, TIPRL, SET, PPME1, and ANP32A genes are all overexpressed in patient samples when compared to normal pleural tissue samples (Figures a and b).…”

Section: Resultsmentioning

confidence: 99%

“…(a) Expression of SET, ARPP19, ANP32E, TIPRL, (b) PPME1 and ANP32A in normal pleura and pleural mesothelioma samples from publicly available data set (GSE2549; Gordon et al, ). (c) Overexpression percentage (red portions) of ANP32E, CIP2A (KIAA1524), TIPRL, ANP32A, ARPP19, SET and PPME1 in pleural mesothelioma samples retrieved from cBIOportal (TCGA‐MESO phs000178, (Gao et al, ; Liu et al, ). (d) Overall survival Kaplan‐Meyer curve of concomitant ANP32E and CIP2A altered gene expression in The Cancer Genome Atlas (TCGA) mesothelioma patient data set…”

Section: Resultsmentioning

confidence: 99%

Data mining analysis of the PP2A cell cycle axis in mesothelioma patients

Pippa

Boffo

Odero

et al. 2019

Journal Cellular Physiology

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Mesothelioma is an aggressive tumor that affects thousands of people every year. The therapeutic options for patients are limited; hence, a better understanding of mesothelioma biology is crucial to improve patient survival. To find new molecular targets and therapeutic strategies related to the protein phosphatase 2A (PP2A) network, we analyzed the gene expression of known PP2A inhibitors in mesothelioma patient samples. Our analysis disclosed a general overexpression of all PP2A‐negative regulators in mesothelioma patients. Moreover, the expression of ANP32E and CIP2A genes, increased in 16% and 11% of cases, positively correlates with the ones of all the other PP2A regulators and the ones of the main cyclins and CDKs, suggesting the existence of a feed‐forward loop that might contribute to the mesothelioma progression via PP2A inactivation. Overall, our study indicates the existence of a strategic and targetable axis between PP2A inhibitors (ANP32E and CIP2A) and cell cycle regulators (cyclin B2/CDK1) and provides a valuable rationale for using a personalized combinational therapy approach to improve mesothelioma patient survival.

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Section: Methodsmentioning

confidence: 99%

“…The clinical and follow‐up information of 134 TGCT samples were obtained from a previous TCGA study (Table ). As for the few disease‐specific survival and overall deaths of TGCT patients, we used disease‐free interval (DFI) and progression‐free interval (PFI) as clinical outcome endpoints . We performed a multivariate Cox proportional hazards regression model to calculate the Hazard Ratio (HR), the 95% confidence interval (95% CI), and P ‐values with adjustments for age and tumor stage.…”

Section: Methodsmentioning

confidence: 99%

Comprehensive characterization of cancer‐testis genes in testicular germ cell tumor

Chang

Wang

et al. 2019

Cancer Medicine

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Cancer‐testis (CT) genes are a group of genes restrictedly expressed in testis and multiple cancers and can serve as candidate driver genes participating in the development of cancers. Our previous study identified a number of CT genes in nongerm cell tumors, but their expression pattern in testicular germ cell tumor (TGCT), a cancer type characterized by less genomic alterations, remained largely unknown. In this study, we systematically investigated the expression pattern of CT genes in TGCT samples and evaluated the transcriptome difference between TGCT and normal testis tissues, using datasets from the UCSC Xena platform, The Cancer Genome Atlas (TCGA) and the Genotype‐Tissue Expression (GTEx) project. Pathway enrichment analysis and survival analysis were conducted to evaluate the biological function and prognostic effect of expressed CT genes. We identified that 1036 testis‐specific expressed protein‐coding genes and 863 testis‐specific expressed long noncoding RNAs (lncRNAs) were expressed in TGCT samples, including 883 CT protein‐coding genes and 710 CT lncRNAs defined previously. The number of expressed CT genes was significantly higher in seminomas ( P = 3.48 × 10 −13 ) which were characterized by frequent mutations in driver genes ( KIT , KRAS and NRAS ). In contrast, the number of expressed CT genes showed a moderate negative correlation with the fraction of copy number altered genomes (cor = −0.28, P = 1.20 × 10 −3 ). Unlike other cancers, our analysis revealed that 96.16% of the CT genes were down‐regulated in TGCT samples, while CT genes in stem cell maintenance related pathways were up‐regulated. Further survival analysis provided evidence that CT genes could also predict the prognosis of TGCT patients with both disease‐free interval and progression‐free interval as clinical endpoints. Taken together, our study provided a global view of CT genes in TGCT and provided evidence that CT genes played important roles in the progression and maintenance of TGCT.

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An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

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Cited by 2,292 publications

References 49 publications

Germline variant burden in multidrug resistance transporters is a therapy‐specific predictor of survival in breast cancer patients

Germline variant burden in multidrug resistance transporters is a therapy‐specific predictor of survival in breast cancer patients

Data mining analysis of the PP2A cell cycle axis in mesothelioma patients

Comprehensive characterization of cancer‐testis genes in testicular germ cell tumor

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