Abstract

ObjectiveAn important criterion for colorectal cancer (CRC) screening is the ability to detect lesions at a curable stage. In the present study, we have assessed the integrin α6 subunit transcript (ITGA6) as part of a stool assay for the detection of colorectal lesions.ResultsIn comparison with control samples, ITGA6 levels were found to be significantly increased at all stages (P < 0.01). Receiver operating characteristic analysis revealed areas under the curve of 0.89 for the prediction of CRC with 81% sensitivity and 88% specificity and of 0.90 for the prediction of advanced adenomas (Ad) with 75% sensitivity and 88% specificity. The ITGA6A variant was also found to be increased relative to ITGA6 in stage II and III CRCs. Combining ITGA6 with other selected transcripts and/or immunochemical fecal occult blood test (iFOBT) results further increased sensitivity and specificity for the detection of colorectal lesions.Patients and MethodsITGA6 detection used alone and under various combinations including detection of other mRNA markers and iFOBT was assessed on stool samples obtained from 175 patients (91 CRCs, 24 Ad and 60 healthy controls).ConclusionsThese data confirm the usefulness and reliability of an mRNA stool assay for the detection of colorectal lesions. The validation of additional candidate genes and their analysis in multiplex qPCR represents a powerful and robust approach that can be combined with iFOBT results to improve the detection of colorectal lesions.

Highlights

  • Colorectal cancer (CRC) remains an important cause of death in the Western world [1]

  • These data confirm the usefulness and reliability of an messenger RNAs (mRNAs) stool assay for the detection of colorectal lesions

  • The validation of additional candidate genes and their analysis in multiplex quantitative real-time PCR (qPCR) represents a powerful and robust approach that can be combined with immunochemical fecal occult blood test (iFOBT) results to improve the detection of colorectal lesions

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Summary

Introduction

Colorectal cancer (CRC) remains an important cause of death in the Western world [1]. Because this cancer can be successfully treated before the occurrence of metastasis, early and efficient diagnosis is crucial [2,3,4]. Other non-invasive methods based on the detection of CRC specific markers released by tumor cells exfoliated into the stools by genomic (stool DNA) or transcriptomic (stool RNA) approaches appear promising [3, 13,14,15,16]. The high rates of exfoliation of epithelial cells that remain at least partially preserved as suggested by the ability to detect long fragments of DNA and mRNA as well as even the cells themselves [20,21,22,23,24,25] support the approach

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