Development and Clinical Validation of a Blood Test Based on 29-Gene Expression for Early Detection of Colorectal Cancer

Abstract

Purpose: A blood test for early detection of colorectal cancer is a valuable tool for testing asymptomatic individuals and reducing colorectal cancer-related mortality. The objective of this study was to develop and validate a novel blood test able to differentiate patients with colorectal cancer and adenomatous polyps (AP) from individuals with a negative colonoscopy.Experimental Design: A case-control, multicenter clinical study was designed to collect blood samples from patients referred for colonoscopy or surgery. Predictive algorithms were developed on 75 controls, 61 large AP (LAP) !1 cm, and 45 colorectal cancer cases and independently validated on 74 controls, 42 LAP, and 52 colorectal cancer cases (23 stages I-II) as well as on 245 cases including other colorectal findings and diseases other than colorectal cancer. The test is based on a 29-gene panel expressed in peripheral blood mononuclear cells alone or in combination with established plasma tumor markers.Results: The 29-gene algorithm detected colorectal cancer and LAP with a sensitivity of 79.5% and 55.4%, respectively, with 90.0% specificity. Combination with the protein tumor markers carcinoembryonic antigen (CEA) and CYFRA21-2 resulted in a specificity increase (92.2%) with a sensitivity for colorectal cancer and LAP detection of 78.1% and 52.3%, respectively.Conclusions: We report the validation of a novel blood test, Colox Ò , for the detection of colorectal cancer and LAP based on a 29-gene panel and the CEA and CYFRA21-1 plasma biomarkers. The performance and convenience of this routine blood test provide physicians a useful tool to test average-risk individuals unwilling to undergo upfront colonoscopy.

Cross-sectional analysis of circulating tumor DNA in primary colorectal cancer at surgery and during post-surgery follow-up by liquid biopsy

“…Thus, ctDNA poorly correlates with yet another classical CRC readout, opening the possibility to integrate ctDNA and CEA into a single early-detection multimarker assay. From the available data, it appears that our results and conclusions are similar, although not identical, to those by Ciarloni et al [25] and Cohen et al [28].…”

“…In addition, although based on molecular barcoding, the TST panel used for LB was not specifically designed for low-noise variant calling. With these caveats and limitations, the reported ctDNA sensitivities by ourselves, Ciarloni et al and Cohen et al [25,28] are not drastically different (58.8% vs 78 and 65%, approximately), and invariably lower than those (93%) reported in metastatic cancer [13]. We conclude that even simple LB assays, like the one described herein, may find immediate clinical application in conditions of low CRC burden.…”

“…Whereas a large number of studies have addressed mCRC [15][16][17][18][19][20][21][22][23] only a few have investigated the role of liquid biopsy in early, non-metastatic CRC patients at surgery, e.g. in conditions of extremely low tumor burden [24][25][26][27][28]. Reinert et al [26] applied genome-wide sequencing to a small pilot cohort.…”

Nanowire Sensors in Cancer

“…Owing to inter-and intrapatient heterogeneity, a cancer marker that combines multiple analytes and functions as a signature is more specific and sensitive. For example, Colox 1 , a blood test based on a 29-gene panel, detects colorectal cancer and large adenomatous polyps with sensitivities of 78.1% and 52.3%, respectively, with 92.20% specificity [34]. Volatile organic compounds (VOCs) from the TME are detectable at the very early stages of cancer and have been used for the early diagnosis of lung, head and neck, breast, gastric, and liver cancers as well as in mesothelioma [35].…”

Biomarkers for Early Cancer Diagnosis: Prospects for Success through the Lens of Tumor Genetics

“…For instance, testing for 29 genes expressed in peripheral blood mononuclear cells and for two proteinaceous plasma biomarkers (carcinoembryonic antigen and CYFRA21‐1) had 92.2% specificity and 78.1% sensitivity for the early detection of colorectal cancer. [ 48 ]…”