Circulating let-7e-5p, miR-106a-5p, miR-28-3p, and miR-542-5p as a Promising microRNA Signature for the Detection of Colorectal Cancer

Abstract

Colorectal cancer (CRC) is a disease with high incidence and mortality. Colonoscopy is a gold standard among tests used for CRC traceability. However, serious complications, such as colon perforation, may occur. Non-invasive diagnostic procedures are an unmet need. We aimed to identify a plasma microRNA (miRNA) signature for CRC detection. Plasma samples were obtained from subjects (n = 109) at different stages of colorectal carcinogenesis. The patients were stratified into a non-cancer (27 healthy volunteers, 17 patients with hyperplastic polyps, 24 with adenomas), and a cancer group (20 CRC and 21 metastatic CRC). miRNAs (381) were screened by TaqMan Low-Density Array. A classifier based on four differentially expressed miRNAs (miR-28-3p, let-7e-5p, miR-106a-5p, and miR-542-5p) was able to discriminate cancer versus non-cancer cases. The overexpression of these miRNAs was confirmed by RT-qPCR, and a cross-study validation step was implemented using eight data series retrieved from Gene Expression Omnibus (GEO). In addition, another external data validation using CRC surgical specimens from The Cancer Genome Atlas (TCGA) was carried out. The predictive model’s performance in the validation set was 76.5% accuracy, 59.4% sensitivity, and 86.8% specificity (area under the curve, AUC = 0.716). The employment of our model in the independent publicly available datasets confirmed a good discrimination performance in five of eight datasets (median AUC = 0.823). Applying this algorithm to the TCGA cohort, we found 99.5% accuracy, 99.7% sensitivity, and 90.9% specificity (AUC = 0.998) when the model was applied to solid colorectal tissues. Overall, we suggest a novel signature of four circulating miRNAs, i.e., miR-28-3p, let-7e-5p, miR-106a-5p, and miR-542-5p, as a predictive tool for the detection of CRC.

Exosomes from mmu_circ_0001052-modified adipose-derived stem cells promote angiogenesis of DFU via miR-106a-5p and FGF4/p38MAPK pathway

“…We found that high glucose increased miR-106a-5p in HUVECs. MiR-106a-5p, a member of miRNA family, plays the molecular regulatory role in multiple sclerosis, colorectal cancer and other chronic diseases [ 27 – 29 ]. Commonly, mmu_circ_0001052 could be involved in cell process by targeting miRNAs.…”

Dynamic liquid biopsy components as predictive and prognostic biomarkers in colorectal cancer

“…Several exosomal miRNAs have also been found differentially expressed in CRC patients and reported as potential biomarkers for the CRC clinical diagnosis [ 53 – 55 ]. A study by Karimi et al identified 11 miRNAs and found that out of these 11 miRNAs, the expression of miR-23a and miR-301a was significantly higher in serum exosomes from CRC patients as compared to healthy controls [ 56 ].…”

Elevated LINC00894 relieves the oncogenic properties of thyroid cancer cell by sponging let-7e-5p to promote TIA-1 expression

“…Previous studies have demonstrated that let-7e-5p was significantly downregulated and let-7e-5p inhibited tumorigenesis and aggressive behavior in head and neck squamous cell carcinoma and non-small cell lung cancer [ 25 , 26 ]. Conversely, let-7e-5p was significantly upregulated in young patients with oral cavity cancer, colorectal cancer, and rectal carcinoma with liver metastases and promoted the tumorigenesis and aggressive behavior of cancer cells [ 27 – 29 ]. Similarly, let-7e-5p was overexpressed in thyroid cancer cells, and a high level of let-7e-5p was correlated with poor prognosis.…”