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

Martha L Slattery,Erica Wolff,Lila E Mullany,Daniel F Pellatt,Michael D Hoffman,Wade Samowitz,Roger K Wolff,Jennifer S Herrick,John R Stevens

doi:10.18632/oncotarget.11173

Abstract

BackgroundMicroRNAs (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).ResultsIndividuals 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 MethodsThis 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.ConclusionsMiRNAs dysregulated for both colon and rectal cancer had a greater impact on survival after a diagnosis with rectal cancer.

Highlights

MicroRNAs are small non-coding RNAs that regulate gene expression and are involved in numerous physiological and cellular processes, including tumor initiation and growth, cell proliferation, apoptosis, and angiogenesis [1,2,3]
Two miRNAs infrequently expressed in the population and not previously reported were associated with survival after diagnosis with colon cancer
Among those diagnosed with rectal cancer, 201 miRNAs were associated with survival when the false discovery rate (FDR) q value was < 0.05

Summary

Introduction

MicroRNAs (miRNA) are small non-coding RNAs that regulate gene expression and are involved in numerous physiological and cellular processes, including tumor initiation and growth, cell proliferation, apoptosis, and angiogenesis [1,2,3]. Given the extensive role of miRNAs in gene regulation and cellular processes, the evaluation of miRNAs as regulators of tumor aggressiveness and prognosis is of interest [5, 6]. To this end, several miRNAs have been shown to be associated with either disease stage or survival after diagnosis with CRC [7]. MiRNA expression may alter survival after diagnosis with colorectal cancer (CRC)

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Results

Conclusion