Messenger RNA (mRNA) stool based biomarkers represent a promising approach for the diagnosis of colorectal cancer (CRC) and advanced precancerous lesions (AA). But it is unclear which mRNA biomarkers have the most clinical utility. This study aims to partially fill this gap by performing an analysis which first ranks genes based on their expression profile in RNA-seq tissue datasets.

The diagnostic performance of the top 20 ranked genes was then tested using 113 clinical samples (CRC N=33, AA N=28, Controls N=53). Fourteen of the genes had significant differential expression in the stool of CRC patients compared to controls (false discovery rate or FDR < 0.05). The Pearson correlation coefficient between tissue and stool expression was 0.57 (p-value = 0.007). The combined performance of the 20 genes in clinical stool samples had an area under the receiver operator curve (AUC) of 0.94 for CRC detection (sensitivity 75.5%, specificity 95%) and an AUC of 0.83 (sensitivity 55.8%, specificity 92.6%) for AA detection. The ability to use existing public transcriptomic datasets to identify promising candidate genes can substantially reduce the cost and effort required to screen for clinically useful mRNA biomarkers.

Loren Hansen, Xiao Yang, Wenying Pan, Changpu Song, Haijiu Lin, Dan Chen all work for companies involved in colorectal cancer diagnostic research. (El Capitan Biosciences and Guangdong Jiyin Biotech)

This study was funded by El Capitan Biosciences.

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The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

Ethics Committee of Shenzhen Nanshan Peoples Hospital Approval number KY-2020-045-01 gave ethical approval for this work.

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All data produced in the present study may be available upon request to the the authors.