Multi-omics Approach Reveals Distinct Differences in Left- and Right-Sided Colon Cancer

• Published in: Molecular cancer research Vol. 16; no. 3; pp. 476 - 485
• Main Authors: Hu, Wangxiong, Yang, Yanmei, Li, Xiaofen, Huang, Minran, Xu, Fei, Ge, Weiting, Zhang, Suzhan, Zheng, Shu
• Format: Journal Article
• Language: English
• Published: United States American Association for Cancer Research Inc 01.03.2018
• Subjects: 1-Phosphatidylinositol 3-kinase; Cancer; Colon; Colon cancer; Colorectal cancer; Colorectal carcinoma; Colorectal Neoplasms - genetics; Colorectal Neoplasms - metabolism; Colorectal Neoplasms - pathology; Crosstalk; Deoxyribonucleic acid; DNA; DNA methylation; Female; Gene expression; Genomes; Humans; Male; Medical prognosis; miRNA; p53 Protein; Prognosis; Prostate cancer; Ribonucleic acid; RNA; Signal transduction; Signaling; Survival
• ISSN: 1541-7786; 1557-3125
• DOI: 10.1158/1541-7786.MCR-17-0483

Increasing evidence suggests that left-sided colon cancer (LCC) and right-sided colon cancer (RCC) are emerging as two different colorectal cancer types with distinct clinical characteristics. However, the discrepancy in the underlying molecular event between these types of cancer has not been thoroughly elucidated to date and warrants comprehensive investigation. To this end, an integrated dataset from The Cancer Genome Atlas was used to compare and contrast LCC and RCC, covering mutation, DNA methylation, gene expression, and miRNA. Briefly, the signaling pathway cross-talk is more prevalent in RCC than LCC, such as RCC-specific PI3K pathway, which often exhibits cross-talk with the RAS and P53 pathways. Meanwhile, methylation signatures revealed that RCC was hypermethylated relative to LCC. In addition, differentially expressed genes ( = 253) and differentially expressed miRNAs ( = 16) were determined between LCC and RCC. Especially for Prostate Cancer Susceptibility Candidate 1 ( ), a gene that was closely associated with hypermethylation, was the top significantly downregulated gene in RCC. Multi-omics comparison of LCC and RCC suggests that there are more aggressive markers in RCC and that tumor heterogeneity occurs within the location-based subtypes of colon cancer. These results clarify the debate regarding the conflicting prognosis between LCC and RCC, as proposed by different studies. The underlying molecular features present in LCC and RCC identified in this study are beneficial for adopting reasonable therapeutic approaches to prolong overall survival and progression-free survival in colorectal cancer patients. .