Dataset Information

Allele Loss and Reduced Expression of CYCLOPS Genes is a Characteristic Feature of Chromophobe Renal Cell Carcinoma.

ABSTRACT: Copy-number alterations Yielding Cancer Liabilities Owing to Partial losS (CYCLOPS) genes have been recently identified as the most enriched class of copy-number associated gene dependencies in human cancer. These genes are cell essential and render tumor cells highly sensitive to the expression of the remaining copy. Chromophobe renal cell carcinoma (chRCC) is characterized by frequent chromosomal deletions, but the relevance of CYCLOPS genes in this tumor subtype is unclear. We found 39 (31%) of 124 recently published candidate CYCLOPS genes (B. Paolella et al., eLife 2017;6:e23268) located on 7 autosomes that are frequently lost in chRCC. GISTIC and RNA-seq data obtained from the TCGA-KICH database showed that 62% of these CYCLOPS genes had significantly lower expression levels in samples with deletion of the respective gene. As copy number (CN) loss of the CYCLOPS gene SF3B1 (Splicing factor 3B subunit 1) has been recently reported in 71% chRCC, we explored the relevance of SF3B1 CN alteration and SF3B1 expression in a set of chRCC and additional oncocytic renal neoplasms. The frequency of SF3B1 CN loss (65%) was similar to that obtained from the TCGA-KICH database and correlated significantly with both lower SF3B1 mRNA (P?

SUBMITTER: Ohashi R

PROVIDER: S-EPMC6563336 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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Allele Loss and Reduced Expression of CYCLOPS Genes is a Characteristic Feature of Chromophobe Renal Cell Carcinoma.

Ohashi Riuko R Schraml Peter P Batavia Aashil A Angori Silvia S Simmler Patrik P Rupp Niels N Ajioka Yoichi Y Oliva Esther E Moch Holger H

Translational oncology 20190611 9

Copy-number alterations Yielding Cancer Liabilities Owing to Partial losS (CYCLOPS) genes have been recently identified as the most enriched class of copy-number associated gene dependencies in human cancer. These genes are cell essential and render tumor cells highly sensitive to the expression of the remaining copy. Chromophobe renal cell carcinoma (chRCC) is characterized by frequent chromosomal deletions, but the relevance of CYCLOPS genes in this tumor subtype is unclear. We found 39 (31%) ...[more]

PMID: 31200327

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Project description:The present techniques of clinical and histopathological diagnosis hardly distinguish chromophobe renal cell carcinoma (ChRCC) from renal oncocytoma (RO). To identify differentially expressed genes (DEGs) as effective biomarkers for diagnosis and prognosis of ChRCC and RO, three mRNA microarray datasets (GSE12090, GSE19982, and GSE8271) were downloaded from the GEO database. Functional enrichment analysis of DEGs was performed by DAVID. STRING and Cytoscape were applied to construct the protein-protein interaction (PPI) network and key modules of DEGs. Visualized plots were conducted by the R language. We downloaded clinical data from the TCGA database and the influence of key genes on the overall survival of ChRCC was performed by Kaplan-Meier and Cox analyses. Gene set enrichment analysis (GSEA) was utilized in exploring the function of key genes. A total of 79 DEGs were identified. Enrichment analyses revealed that the DEGs are closely related to tissue invasion and metastasis of cancer. Subsequently, 14 hub genes including ESRP1, AP1M2, CLDN4, and CLDN7 were detected. Kaplan-Meier analysis indicated that the low expression of CLDN7 and GNAS was related to the worse overall survival in patients with ChRCC. Univariate Cox analysis showed that CLDN7 might be a helpful biomarker for ChRCC prognosis. Subgroup analysis revealed that the expression of CLDN7 showed a downtrend with the development of the clinical stage, topography, and distant metastasis of ChRCC. GSEA analysis identified that cell adhesion molecules cams, B cell receptor signaling pathway, T cell receptor signaling pathway, RIG-I like receptor signaling pathway, Toll-like receptor signaling pathway, and apoptosis pathway were associated with the expression of CLDN7. In conclusion, ESRP1, AP1M2, CLDN4, PRSS8, and CLDN7 were found to distinguish ChRCC from RO. Besides, the low expression of CLDN7 was closely related to ChRCC progression and could serve as an independent risk factor for the overall survival in patients with ChRCC.

Dataset Information

Allele Loss and Reduced Expression of CYCLOPS Genes is a Characteristic Feature of Chromophobe Renal Cell Carcinoma.

Publications

Allele Loss and Reduced Expression of CYCLOPS Genes is a Characteristic Feature of Chromophobe Renal Cell Carcinoma.

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