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

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.Colorectal cancer (CRC) is a common disease affecting over a million people annually, worldwide. 1 Novel cytotoxic agents alone or in combination with targeted systemic therapy significantly improve median survival in patients with advanced or metastatic CRC. These adjuvant therapeutic agents reduce the risk of disease-recurrence in patients who undergo complete resection of CRC, but are at high risk of disease relapse. Despite major advances in systemic therapy for CRC, nearly 50% of patients diagnosed with this common malignancy will recur and die of disease within 5 years of diagnosis and treatment with curative intent. 2 To improve overall outcome of this disease, prevention and early detection through effective screening methods are imperative.Current CRC screening and diagnosis is based mainly on fecal occult blood testing (FOBT) and fiber-optic colonoscopy, both which have demonstrated clinical utility and efficacy in early diagnosis and reduction of CRC-related mortality. 3,4 Recently, stool-based DNA assays were developed for

Pan-cancer transcriptome analysis reveals long noncoding RNAs with conserved function

“…Several well-studied lncRNAs are included in our list of oncolncRNAs, including: CCAT1, 31 (Table S6). Additionally, many well-characterized lncRNAs, such as ANRIL and MALAT1, are altered in only a single cancer within our cohort and thus are not considered to be onco-lncRNAs.…”

Colorectal cancer carcinogenesis: a review of mechanisms

“…In vivo studies indicate PRKA kinase anchor protein 9 (AKAP-9) as a target gene of MALAT-1. Its upregulation is correlated with MALAT-1 tumor promoting activity 188 .…”

Long non-coding RNAs in colorectal cancer: implications for pathogenesis and clinical application

“…6,7,[79][80][81] Notably, similar to other nucleic acids, lncRNAs can also be present in peripheral blood components, such as serum, plasma, and peripheral blood mononuclear cells. [82][83][84] The peripheral lncRNA profiles may potentially contribute to the characterization of novel biomarkers for CRC patients. Indeed, some lncRNAs appear to have strong diagnostic potential as blood biomarkers for colorectal neoplasia.…”

“…Recently, based on its unique expression characteristics in CRC, the lncRNA CCAT1 has emerged as a potential biomarker for screening precancerous lesions. CCAT1 is markedly overexpressed in CRC 84 and is also upregulated in precancerous tissues, including benign inflammatory colonic tissues and adenomatous polyps. 85 CCAT1 can be detected in CRC tissue and in the blood and stool samples of CRC patients.…”