LGALS4, CEACAM6, TSPAN8, and COL1A2: Blood Markers for Colorectal Cancer-Validation in a Cohort of Subjects With Positive Fecal Immunochemical Test Result

Abstract

Background: A noninvasive blood test for the early detection of colorectal cancer (CRC) is highly required. We evaluated a panel of 4 mRNAs as putative markers of CRC.

Materials and methods: We tested LGALS4, CEACAM6, TSPAN8, and COL1A2, referred to as the CELTiC panel, using quantitative reverse transcription polymerase chain reaction, on subjects with positive fecal immunochemical test (FIT) results and undergoing colonoscopy. Using a nonparametric test and multinomial logistic model, FIT-positive subjects were compared with CRC patients and healthy individuals.

Results: All the genes of the CELTiC panel displayed statistically significant differences between the healthy subjects (n = 67), both low-risk (n = 36) and high-risk/CRC (n = 92) subjects, and those in the negative-colonoscopy, FIT-positive group (n = 36). The multinomial logistic model revealed LGALS4 was the most powerful marker discriminating the 4 groups. When assessing the diagnostic values by analysis of the areas under the receiver operating characteristic curves (AUCs), the CELTiC panel reached an AUC of 0.91 (sensitivity, 79%; specificity, 94%) comparing normal subjects to low-risk subjects, and 0.88 (sensitivity, 75%; specificity, 87%) comparing normal and high-risk/CRC subjects. The comparison between the normal subjects and the negative-colonoscopy, FIT-positive group revealed an AUC of 0.93 (sensitivity, 82%; specificity, 97%).

Conclusion: The CELTiC panel could represent a useful tool for discriminating subjects with positive FIT findings and for the early detection of precancerous adenomatous lesions and CRC.

Keywords: CRC; Colonoscopy; FIT; Fecal occult blood test; Liquid biopsy.