Journal
INTERNATIONAL JOURNAL OF CANCER
Volume 140, Issue 1, Pages 176-187Publisher
WILEY
DOI: 10.1002/ijc.30433
Keywords
circulating miRNA; miR-200 family; miR-122; CRC; prognosis
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Circulating microRNAs (miRNAs) have been proposed as minimally invasive prognostic markers for various types of cancers, including colorectal cancer (CRC), the third most diagnosed cancer worldwide. We aimed to evaluate the levels of circulating miRNAs that might serve as markers for CRC prognosis and survival. We included plasma samples of 543 CRC patients with stage I-IV disease from a population-based study carried out in Germany. After comprehensive evaluation of current literature, 95 miRNAs were selected and measured with Custom TaqMan (R) Array MicroRNA Cards. Plasma samples of non-metastatic and metastatic colon cancer patients, each group consisting of ten patients with good' and ten patients with bad' prognosis were screened. Identified candidate miRNAs were further validated by RT-qPCR in the whole study cohort. The association of the miRNA levels with patients' survival and the prognostic subtypes was analyzed with uni- and multivariate logistic regression and Cox proportional hazards regression models. Increased miR-122 levels were associated with a bad' prognostic subtype in metastatic CRC (Odds ratio: 1.563, 95% confidence interval (CI): 1.038-2.347) and a shorter relapse-free survival and overall survival for non-metastatic (Hazard ratio (HR): 1.370, 95% CI: 1.028-1.825; HR: 1.353, 95% CI: 1.002-1.828) and metastatic (HR: 1.264, 95% CI: 1.050-1.520; HR: 1.292, 95% CI: 1.078-1.548) CRC patients. Additionally, several members of the miR-200 family showed associations with patients' prognosis and correlations to clinicopathological characteristics. The here identified miRNA markers, miR-122 and the miR-200 family members, could be of use in the development of a multi-marker blood test for CRC prognosis. What's new? Metastasis is the major cause of death for colorectal cancer (CRC) patients. Prognostic markers that are constantly measurable using liquid biopsies could facilitate the earlier prediction of relapse events and metastasis formation. In a prospective study cohort of 543 colorectal cancer patients, the authors evaluated the role of circulating miRNAs as potential prognostic markers for CRC with a specific focus on miRNAs known to be involved in tumor progression and metastasis formation. MiR-122 and several members of the miR-200 family were identified as prognostic markers, suggesting their potential use in the development of a multi-marker blood test for CRC prognosis.
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