American Association for Cancer Research
00085472can120656-sup-t3_50k.pdf (50.12 kB)

Supplementary Table 3 from Multilevel Whole-Genome Analysis Reveals Candidate Biomarkers in Clear Cell Renal Cell Carcinoma

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journal contribution
posted on 2023-03-30, 21:06 authored by Andrew H. Girgis, Vladimir V. Iakovlev, Ben Beheshti, Jane Bayani, Jeremy A. Squire, Anna Bui, Marina Mankaruos, Youssef Youssef, Bishoy Khalil, Heba Khella, Maria Pasic, George M. Yousef

PDF file - 50K, Significantly expressed genes located on the 3p and 5q chromosomal arms among aberrant versus normal kidney and integration of protein and miRNA data in ccRCC



Renal cell carcinoma (RCC) is the most common neoplasm of the kidney. We conducted an integrated analysis of copy number, gene expression (mRNA and miRNA), protein expression, and methylation changes in clear cell renal cell carcinoma (ccRCC). We used a stepwise approach to identify the most significant copy number aberrations (CNA) and identified regions of peak and broad copy number gain and loss, including peak gains (3q21, 5q32, 5q34-q35, 7p11, 7q21, 8q24, 11q13, and 12q14) and deletions (1p36, 2q34-q37, 3p25, 4q33-q35, 6q23-q27, and 9p21). These regions harbor novel tumor-related genes and miRNAs not previously reported in renal carcinoma. Integration of genome-wide expression data and gene set enrichment analysis revealed 75 gene sets significantly altered in tumors with CNAs compared with tumors without aberration. We also identified genes located in peak CNAs with concordant methylation changes (hypomethylated in copy number gains such as STC2 and CCND1 and hypermethylated in deletions such as CLCNKB, VHL, and CDKN2A/2B). For other genes, such as CA9, expression represents the net outcome of opposing forces (deletion and hypomethylation) that also significantly influences patient survival. We also validated the prognostic value of miRNA let-7i in RCCs. miR-138, located in chromosome 3p deletion, was also found to have suppressive effects on tumor proliferation and migration abilities. Our findings provide a significant advance in the delineation of the ccRCC genome by better defining the impact of CNAs in conjunction with methylation changes on the expression of cancer-related genes, miRNAs, and proteins and their influence on patient survival. Cancer Res; 72(20); 5273–84. ©2012 AACR.