Serum exosomal miR-122 as a potential diagnostic and prognostic biomarker of colorectal cancer with liver metastasis

Abstract

Background: Liver is the most common site for metastatic spread of CRC at the time of diagnosis which leads to high mortality. This study aimed to identify novel circulating exosomal miRNAs as biomarkers of colorectal cancer (CRC) with liver metastasis (LM). Materials and methods: Candidate miRNAs were selected through integrated analysis of Gene Expression Omnibus (GEO) database as well as clinical samples. Exosomes isolated from serum and cultured media were identified by using transmission electron microscopy (TEM) and western blot. The expression levels and diagnostic value of candidate miRNAs were further tested and validated through qRT-PCR and receiver operating characteristic curve (ROC) analysis. The association of candidate miRNA expressions with patients' prognosis was analyzed with logistic regression and Cox proportional hazards regression models. Results: After integrated analysis of three GEO datasets and clinical samples, miR-122 was discovered to be remarkably overexpressed in tissues of CRC patients. Then we revealed that elevated serum miR-122 was tumor-derived by being packaged into exosomes. The expressions of serum exosomal miR-122 were significantly upregulated in CRC patients, especially in those with LM. Serum exosomal miR-122 expressions could differentiate CRC patients with LM from healthy controls and patients without LM with area under the ROC curve (AUC) of 0.89 and 0.81. Uni-and multivariate logistic regression showed that serum exosomal miR-122 was an independent prognostic indicator of CRC patients. Conclusions: Serum exosomal miR-122 was a novel potential diagnostic and prognostic biomarker in CRC patients with LM.

Serum microRNA‑592 serves as a novel potential biomarker for early diagnosis of colorectal cancer

“…It is speculated that the combination of currently available tumor biomarkers with miR-592 may improve the diagnostic value or sensitivity and specificity for patients with CRC. Previous studies have reported that tumor cells secrete miRNAs into circulation via exosomes (33)(34)(35); however, this phenomenon was not investigated in the present study. Thus, future studies will aim to determine whether CRC cells have the ability to release miR-592.…”

Construction and Prognostic Analysis of miRNA-mRNA Regulatory Network in Liver Metastasis from Colorectal Cancer

“…[38] Meanwhile, high levels of hsa-miR-122-5p in plasma may indicate colorectal cancer liver metastasis and be associated with shorter relapse-free survival (RFS)and overall survival (OS) time. [39,40] Analysis of differential expression in the invasion front of CRC with early lymph node metastasis reveals high expression of hsa-miR-17-3p, [41]which may enhance the proliferation and inhibit apoptosis of CRC cells by targeting Prostate apoptosis responde-4 (Par4). [42] hsa-miR-33b-5p was shown to constrain tumor cell growth and induce cell cycle arrest, and decreased expression level in liver cancer and CRC, which is inconformity with the results of this paper.…”

Clinical diagnostic value of long non-coding RNAs in Colorectal Cancer: A systematic review and meta-analysis

“…Recent studies have suggested that the expression of lncRNAs in CRC might be involved in cancer development, invasion, metastasis, prognosis [33][34][35][36]. Statistically significant differences in the expression of lncRNAs between precancerous lesions and early-stage cancer have been found in previous studies [37][38][39]. However, there is no relevant systematic review and meta-analyses focused on the expression of lncRNAs in CRC diagnosis.…”