Stratification of Digestive Cancers with Different Pathological Features and Survival Outcomes by MicroRNA Expression

Abstract

MicroRNAs (miRNAs) are aberrantly expressed in virtually all cancer types, including digestive cancers. Herein, we aggregated and systematically analyzed miRNA expression profiles of 1765 tumor samples, including esophageal, gastric, liver, pancreatic, colon and rectal cancers, obtained through small RNA sequencing by The Cancer Genome Atlas. We found that digestive cancers of different tissue origins could be differentiated according to their miRNA expression profiles. In particular, esophageal squamous cell carcinoma and esophageal adenocarcinoma exhibited distinct miRNA expression patterns. Thirteen (e.g. miR-135b, miR-182) and sixteen (e.g. miR-139, miR-133a-1, miR-490) miRNAs were commonly upregulated and downregulated in more than four cancer types, respectively. Pertinent to pathological features, low miR-181d expression was associated with microsatellite instability in colon and gastric cancers whereas low miR-106a expression was associated with hepatitis B virus infection in hepatocellular carcinoma. Progression in colon cancer could also be predicted by low let-7f-2 and high miR-106a expression. Molecular subtypes with distinct prognostic outcomes independent of tumor-node-metastasis staging were identified in hepatocellular carcinoma and colon cancer. In total, 4 novel and 6 reported associations between specific miRNAs and patients’ survival were identified. Collectively, novel miRNA markers were identified to stratify digestive cancers with different pathological features and survival outcomes.

Common Deregulation of Seven Biological Processes by MicroRNAs in Gastrointestinal Cancers

“…Since deregulation of epidermal growth factor receptor (EGFR) signaling commonly occurs in colorectal cancer and contributes to its progression, we decided to study how two selected miRNAs, namely miR-17 and miR-145, would affect EGFR endocytosis. Both miR-17 and miR-145 have been identified as two of the most common differentially expressed miRNAs across digestive cancers in our meta-analysis of small RNA sequencing data from The Cancer Genome Atlas 16 . SW1116, a KRAS -wild-type colon cancer cell line, was transfected with control miRNA, miR-17 or miR-145.…”

The Natural Flavonoid Fisetin Inhibits Cellular Proliferation of Hepatic, Colorectal, and Pancreatic Cancer Cells through Modulation of Multiple Signaling Pathways

“…Digestive cancers are major causes of cancer mortality and morbidity in the world [1]. Gastrointestinal cancers include malignancies arising in the esophagus, gallbladder, pancreas, liver and bile ducts, small intestine, stomach, colon and rectum.…”

A coordinate deregulation of microRNAs expressed in mucosa adjacent to tumor predicts relapse after resection in localized colon cancer

“…colonic polyps [ 8 ], and it has been suggested as a prognostic factor for survival of post-operative CRC patients [ 9 ]. The increased expression of miR-183 and miR-182, both members of miR-183 cluster, has been related to advanced clinical stage, lymph node involvement, distant metastases and poor prognosis [ 10 , 11 ]. Concerning miR-139, a recent study highlighted its down-regulation in colon cancer cell lines and patients and its association with metastasis and drug resistance [ 12 ].…”