Colon cancer associated transcript‐1: A novel RNA expressed in malignant and pre‐malignant human tissues

TLDR

Early detection of colorectal cancer relies on fecal occult blood testing and colonoscopy, yet these methods suffer from low sensitivity, specificity, and high labor and cost burdens. The study aims to discover novel biomarkers that can improve colorectal cancer screening, diagnosis, staging, and therapeutic targeting. The authors employed representational difference analysis to identify and characterize CCAT1, a transcript strongly expressed in colon adenocarcinoma but largely absent in normal tissues. CCAT1 is expressed on average 235‑fold higher in colorectal cancer than in normal mucosa, is present in early tumorigenesis stages such as adenomatous polyps and tumor‑proximal epithelium, is detectable in all H&E‑positive lymph nodes and 40 % of negative nodes, and appears in 40 % of peripheral blood samples from CRC patients but not in healthy controls, making it a highly specific and sensitive marker.

Abstract

Abstract Early detection of colorectal cancer (CRC) is currently based on fecal occult blood testing (FOBT) and colonoscopy, both which can significantly reduce CRC‐related mortality. However, FOBT has low‐sensitivity and specificity, whereas colonoscopy is labor‐ and cost‐intensive. Therefore, the discovery of novel biomarkers that can be used for improved CRC screening, diagnosis, staging and as targets for novel therapies is of utmost importance. To identify novel CRC biomarkers we utilized representational difference analysis (RDA) and characterized a colon cancer associated transcript (CCAT1), demonstrating consistently strong expression in adenocarcinoma of the colon, while being largely undetectable in normal human tissues ( p < 000.1). CCAT1 levels in CRC are on average 235‐fold higher than those found in normal mucosa. Importantly, CCAT1 is strongly expressed in tissues representing the early phase of tumorigenesis: in adenomatous polyps and in tumor‐proximal colonic epithelium, as well as in later stages of the disease (liver metastasis, for example). In CRC‐associated lymph nodes, CCAT1 overexpression is detectable in all H&E positive, and 40.0% of H&E and immunohistochemistry negative lymph nodes, suggesting very high sensitivity. CCAT1 is also overexpressed in 40.0% of peripheral blood samples of patients with CRC but not in healthy controls. CCAT1 is therefore a highly specific and readily detectable marker for CRC and tumor‐associated tissues.