Circulating miRNA as Biomarkers for Colorectal Cancer Diagnosis and Liver Metastasis

Abstract

Colorectal cancer (CRC) is the second leading cause of cancer deaths worldwide. Stage IV CRC patients have poor prognosis with a five-year survival rate of 14%. Liver metastasis is the main cause of mortality in CRC patients. Since current screening tests have several drawbacks, effective stable non-invasive biomarkers such as microRNA (miRNA) are needed. We aim to investigate the expression of miRNA (miR-21, miR-19a, miR-23a, miR-29a, miR-145, miR-203, miR-155, miR-210, miR-31, and miR-345) in the plasma of 62 Lebanese Stage IV CRC patients and 44 healthy subjects using RT-qPCR, as well as to evaluate their potential for diagnosis of advanced CRC and its liver metastasis using the Receiver Operating Characteristics (ROC) curve. miR-21, miR-145, miR-203, miR-155, miR-210, miR-31, and miR-345 were significantly upregulated in the plasma of surgery naïve CRC patients when compared to healthy individuals. We identified two panels of miRNA that could be used for diagnosis of Stage IV CRC (miR-21 and miR-210) with an area under the curve (AUC) of 0.731 and diagnostic accuracy of 69% and liver metastasis (miR-210 and miR-203) with an AUC = 0.833 and diagnostic accuracy of 72%. Panels of specific circulating miRNA, which require further validation, could be potential non-invasive diagnostic biomarkers for CRC and liver metastasis.

miRNAs in Cancer (Review of Literature)

“…Examination of miRNAs for specific fractions can significantly increase both the sensitivity and specificity of selected circulating miRNAs as noninvasive biomarkers [ 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 ].…”

MicroRNAs and ‘Sponging’ Competitive Endogenous RNAs Dysregulated in Colorectal Cancer: Potential as Noninvasive Biomarkers and Therapeutic Targets

“…Similar to other miRNAs, miR-203's activity can be halted by means of sponging by ncRNAs, such as FBXL19-AS1 [236], BANCR [237], and LINC00657 [238]. Many studies into the serum/plasma levels of miR-203 in CRC patients have discovered that differential levels of miR-203 are most often an indicator of poor prognosis and increased metastasis usually marked by an increase in miR-203 [89][90][91][93][94][95][96], with some showing lowered levels [84,92]. A meta-analyses of 11 papers found a higher miR-203 expression in CRC tissue to be significant, and not in serum, but a combination of both serum and CRC tissue was predictive of a poor outcome [239].…”

CRISPR/Cas13-Based Platforms for a Potential Next-Generation Diagnosis of Colorectal Cancer through Exosomes Micro-RNA Detection: A Review

“…Additionally, several studies have indicated that blood samples have emerged as a reliable source of biomarkers [ 127 , 128 ]. Accordingly, cancer-related miRNAs, either CEx-miRNAs or cancer-derived cell-free miRNAs (cf-miRNAs), from blood represents a promising target for more accessible and non-invasive testing [ 129 , 130 ]. In this regard, blood CEx and miRNA extraction can be easily achieved through available commercial kits, delivering precise and valuable diagnostic and prognostic data [ 131 , 132 , 133 ].…”