Circulating microRNA expressions in colorectal cancer as predictors of response to chemotherapy

Abstract

Colorectal cancer (CRC) is the third most frequently diagnosed cancer and the third leading cause of cancer death in the Western world. Chemotherapy has been shown to improve outcomes in patients with CRC; however, only selected patients would benefit from this treatment. We aimed to identify predictors of response to chemotherapy in CRC using circulating microRNAs (miRNAs). We studied differential miRNA expression by miRNA array from serum of 253 patients who had chemotherapy treatment. We screened the differentially expressed serum miRNAs with TaqMan low-density arrays using pooled CRC patient serum samples. Differential expression was validated using hydrolysis probe-based stem-loop quantitative reverse transcription PCR in individual samples. We performed additional unsupervised cluster to analyse the differential expression of serum miRNA between the chemosensitive and chemoresistant patients. A distinct miRNA expression signature in response to chemotherapy was identified. The TaqMan low-density array results demonstrated that 17 serum miRNAs could predict chemosensitivity and chemoresistance. The quantitative reverse transcription PCR analysis further identified a profile of five serum miRNAs (miR-20a, miR-130, miR-145, miR-216 and miR-372) as a biomarker for predicting the chemosensitivity of CRC. The areas under the receiver operating characteristic curve of this five-serum miRNA signature were 0.841 and 0.918 for the two sets of serum samples, respectively. We identified a group of miRNA predictors in response to chemosensitivity for CRC patients. This could lead to a significant improvement in chemotherapy regimen selection strategy and personalized CRC management.

Circulating MicroRNAs in Colorectal Cancer

“…candidate biomarkers for CRC diagnosis, miR-92a was down-regulated in CRC than control samples [18]. The similar contradictory results were also observed in the circulating miRNAs miR-145, miR-150 and miR-203 [19][20][21][22].…”

Biomarkers and Molecular Imaging as Predictors of Response to Neoadjuvant Chemoradiotherapy in Patients With Locally Advanced Rectal Cancer

“…Moreover, like the previously mentioned studies, the dynamic variations in these circulating markers during treatment strongly reflect therapy efficacy, with a significant reduction in hTERT levels only in responsive patients. 70 Although recent findings highlight the correlation between circulating miR expression levels in some tumors, including colorectal cancer, and response to chemotherapy, 71 to our knowledge no studies focused on LARC and NCRT have produced significant results.…”

Circulating microRNAs: emerging biomarkers for diagnosis and prognosis in patients with gastrointestinal cancers

“…They found 17 serum miRNAs correlated with chemosensitivity, and finally selected a panel of five miRNAs (miR-20a, miR-130, miR-145, miR-216 and miR-372), which were significantly downregulated in the responder group. This panel reached an AUC of up to 0.918 for its ability to distinguish between responders and non-responders (AUC for CEA = 0.689 and CA19-9 =0.746) [31]. Finally, another research group compared the expression of 742 miRNAs in plasma samples from cancer patients before commencement and after four cycles of 5-FU/oxaliplatin chemotherapy.…”

“…Circulating miRNAs can originate from 1) active secretion via microversicles (MV) including exosomes [23][24][25], 2) active secretion in a protein / miRNA complex [15,24,25], 3) circulating miRNAs originating from blood cells such as immunocytes [25], and 4) passive secretion by tumor apoptosis and necrosis [24][25][26]. Consequently, when actively secreted, circulating miRNAs can indicate certain characteristics of the underlying tumor such as metastatic potential [27][28][29] or chemosensitivity [30][31][32][33]. Furthermore, when passively secreted, they might be used as biomarkers of cell destruction, for example, in the context of myocardial infarction [26,34] or liver cirrhosis [35].…”