The High Ratio of the Plasma miR-96/miR-99b Correlated With Poor Prognosis in Patients With Metastatic Colorectal Cancer

Abstract

Object: This study aims to clarify the expression of plasma miRNA in CRC patients, and to clarify the potential use of these miRNAs in diagnosis and prognosis, and to establish a prognostic model to initially explore its clinical value.Methods: We detected the expression of 6 miRNAs in normal colon epithelial cell lines and colorectal cancer cell lines by qRT-PCR and they were validated in the tissues of three subtypes: 20 healthy subjects, 41 pCRC and 49 mCRC patients. COX regression and ROC analyses use to evaluate the diagnostic and prognostic efficacy of candidate miRNAs. Subsequently, we initially established a nomogram prognostic model. MiRNA is also used to construct miRNA-mRNA interaction network and PPI network modules.Results: Five miRNAs showed significant differential expression in pCRC, mCRC patients and normal groups. ROC analysis showed that CEA, miR-96, miR-99b and miR-96/miR-99b are distinguishable from pCRC and mCRC patients, with AUC ranging from 0.65 to 0.91; among them, the ratio of miR-96/miR-99b is stronger than any diagnostic indicators, such as CEA and CA125. Multivariate survival analysis identified miR-96, miR-99b, N stage, M stage and clinical stage as independent prognostic indicators of mCRC. The nomogram based on these 5 characteristics has satisfactory prognostic values.Conclusion: Our data indicate that plasma miR-96/miR-99b can be used as a promising biomarker for early detection of mCRC patients; our nomogram has a promising evaluation value.