Detection of serological biomarkers by proximity extension assay for detection of colorectal neoplasias in symptomatic individuals

TLDR

Biomarkers hold promise for early colorectal cancer detection, yet only a few molecular markers are clinically approved. The study aimed to translate biomarkers into practice by evaluating the proximity extension assay and potential additive effects of biomarker panels. Researchers screened 74 plasma biomarkers in a symptomatic case–control cohort, statistically identified 12 significant CRC indicators, and found that a panel of CEA, TFRC, MIF, OPN/SPP1, and CA242 produced additive ROC performance. The five‑protein panel achieved 56 % sensitivity at 90 % specificity for CRC, and a three‑protein subset (CEA, TFRC, CA242) yielded an AUC of 0.861 for early‑stage CRC.

Abstract

Although the potential of biomarkers to aid in early detection of colorectal cancer (CRC) is recognized and numerous biomarker candidates have been reported in the literature, to date only few molecular markers have been approved for daily clinical use. In order to improve the translation of biomarkers from the bench to clinical practice we initiated a biomarker study focusing on a novel technique, the proximity extension assay, with multiplexing capability and the possible additive effect obtained from biomarker panels. We performed a screening of 74 different biomarkers in plasma derived from a case–control sample set consisting of symptomatic individuals representing CRC patients, patients with adenoma, patients with non-neoplastic large bowel diseases and healthy individuals. After statistical evaluation we found 12 significant indicators of CRC and the receiver operating characteristic (ROC) curve of Carcinoembryonic antigen (CEA), Transferrin Receptor-1 (TFRC), Macrophage migration inhibitory factor (MIF), Osteopontin (OPN/SPP1) and cancer antigen 242 (CA242) showed additive effect. This biomarker panel identified CRC patients with a sensitivity of 56% at 90% specificity and thus the performance is sufficiently high to further investigate this combination of five proteins as serological biomarkers for detection of CRC. Furthermore, when applying the indicators to identify early-stage CRC a combination of CEA, TFRC and CA242 resulted in a ROC curve with an area under the curve of 0.861.