A straightforward method to quantify circulating mRNAs as biomarkers of colorectal cancer

一种量化循环 mRNA 作为结直肠癌生物标志物的直接方法

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作者:Marie Grosgeorges #, Laurence Picque Lasorsa #, Brice Pastor #, Corinne Prévostel, Evelyne Crapez, Cynthia Sanchez, Florence Frayssinoux, Marta Jarlier, Véronique Pezzella, Laure Monard, Marc Ychou, Alain R Thierry, Thibault Mazard, Philippe Blache

Abstract

Optimizing the biomarker combination to be analyzed in liquid biopsies should improve personalized medicine. We developed a method to purify circulating cell-free mRNAs from plasma samples and to quantify them by RT-qPCR. We selected three candidate colorectal cancer biomarkers (B2M, TIMP-1, and CLU). Their mRNA levels were significantly higher in plasma of patients with metastatic colorectal cancer patients (mCRC) (n = 107) than in healthy individuals (HI) (n = 53). To increase the discriminating performance of our method, we analyzed the sum of the three mRNA levels (BTC index). The area under the ROC curve (AUC) to estimate the BTC index capacity to discriminate between mCRC and HI plasma was 0.903. We also determined the optimal BTC index cut-off to distinguish between plasma samples, with 82% of sensitivity and 93% of specificity. By using mRNA as a novel liquid biopsy analytical parameter, our method has the potential to facilitate rapid screening of CRCm.

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