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

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.

SUBMITTER: Grosgeorges M

PROVIDER: S-EPMC9932139 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature

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

Grosgeorges Marie M Picque Lasorsa Laurence L Pastor Brice B Prévostel Corinne C Crapez Evelyne E Sanchez Cynthia C Frayssinoux Florence F Jarlier Marta M Pezzella Véronique V Monard Laure L Ychou Marc M Thierry Alain R AR Mazard Thibault T Blache Philippe P

Scientific reports 20230215 1

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 discriminati ...[more]

PMID: 36792801

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Project description:BackgroundProteomics-based technologies are emerging tools used for cancer biomarker discovery. Limited prospective studies have been conducted to evaluate the role of circulating proteins in colorectal cancer (CRC) development.MethodsA two-stage case-control proteomics study nested in the Shanghai Women's Health Study was conducted. A total of 1104 circulating proteins were measured in the discovery phase, consisting of 100 incident CRC cases and 100 individually matched controls. An additional 60 case-control pairs were selected for validation. Protein profiling at both stages was completed using the Olink platforms. Conditional logistic regression was used to evaluate the associations between circulating proteins and CRC risk. The elastic net method was employed to develop a protein score for CRC risk.ResultsIn the discovery set, 27 proteins showed a nominally significant association with CRC risk, among which 22 were positively and 5 were inversely associated. Six of the 27 protein markers were significantly associated with CRC risk in the validation set. In the analysis of pooled discovery and validation sets, odds ratios (ORs) per standard deviation (SD) increase in levels of these proteins were 1.54 (95% confidence interval (CI): 1.15-2.06) for CD79B; 1.71 (95% CI: 1.24-2.34) for DDR1; 2.04 (95% CI: 1.39-3.01) for EFNA4; 1.54 (95% CI: 1.16-2.02) for FLRT2; 2.09 (95% CI: 1.47-2.98) for LTA4H and 1.88 (95% CI: 1.35-2.62) for NCR1. Sensitivity analyses showed consistent associations for all proteins with the exclusion of cases diagnosed within the first two years after the cohort enrollment, except for CD79B. Furthermore, a five-protein score was developed based on the six proteins identified and showed significant associations with CRC risk in both discovery and validation sets (Discovery: OR1-SD = 2.46, 95% CI: 1.53-3.95; validation: OR1-SD = 4.16, 95% CI: 1.92-8.99).ConclusionsA panel of five protein markers was identified as potential biomarkers for CRC risk. Our findings provide novel insights into the etiology of CRC and may facilitate the risk assessment of the malignancy.

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

Publications

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

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