Site-specific associations between miRNA expression and survival in colorectal cancer cases

// Martha L. Slattery 1 , Jennifer S. Herrick 1 , Daniel F. Pellatt 1 , Lila E. Mullany 1, John R. Stevens 2 , Erica Wolff 1 , Michael D. Hoffman 1 , Roger K. Wolff 1, Wade Samowitz 3 1 Department of Medicine, University of Utah, Salt Lake City, Utah 84108, USA 2 Department of Mathematics and Statistics, Utah State University, Logan, Utah 84322, USA 3 Department of Pathology, University of Utah School, Salt Lake City, Utah 84108, USA Correspondence to: Martha L. Slattery, email: marty.slattery@hsc.utah.edu Keywords: colon cancer, rectal cancer, miRNA, disease stage Received: June 04, 2016      Accepted: July 23, 2016      Published: August 10, 2016 ABSTRACT Background: MicroRNAs (miRNA) are small non-coding RNA involved in cellular processes, including cell proliferation and angiogenesis. Thus, miRNA expression may alter survival after diagnosis with colorectal cancer (CRC). Results: Individuals diagnosed with stage 1 or stage 2 rectal cancer had worse survival than colon cancer cases diagnosed at stage 1 or stage 2. After adjustment for multiple comparisons, no miRNAs were significantly associated with disease stage. Two miRNAs infrequently expressed in the population and not previously reported were associated with survival after diagnosis with colon cancer (miR-1 HR 2.17 95% CI 1.41, 3.36; and miR-101-3p HR 3.51 95% CI 1.72, 7.15). Among those diagnosed with rectal cancer, 201 miRNAs were associated with survival when the FDR q value was < 0.05. Assessment of 105 previously reported miRNAs associated with prognosis showed that four miRNAs influenced colon cancer survival and 17 influenced survival after a diagnosis with rectal cancer when raw p values were considered. Patients and Methods: This study includes data from population-based studies of CRC conducted in Utah and the Kaiser Permanente Medical Care Program. A total of 1893 carcinoma and normal paired colorectal mucosa tissue samples were run using the Agilent Human miRNA Microarray V19.0. We assessed miRNA differential expression between paired carcinoma and normal colonic mucosa tissue with CRC- specific survival evaluating stage and site-specific associations after adjusting for age, sex, microsatellite instability tumor status, and AJCC stage. Conclusions: MiRNAs dysregulated for both colon and rectal cancer had a greater impact on survival after a diagnosis with rectal cancer.