IGFBP3 gene promoter methylation analysis and its association with clinicopathological characteristics of colorectal car
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ORIGINAL ARTICLE
IGFBP3 gene promoter methylation analysis and its association with clinicopathological characteristics of colorectal carcinoma Alok Kumar1,2 · Pradyumn Singh2 · Anshuman Pandey3 · Sunil Babu Gosipatala1 Received: 30 December 2019 / Accepted: 28 August 2020 © Springer Nature B.V. 2020
Abstract Promoter methylation mediated silencing of tumor suppressor genes plays an important role in the tumorigenesis of colorectal carcinoma (CRC). Tumor suppressor gene, Insulin-like Growth Factor Binding Protein-3 (IGFBP-3) expression is frequently downregulated in CRC due to promoter methylations. The aim of this study was to analyze the methylation status of IGFBP-3 gene promoter in stage II and III of CRC cases; find its association with clinicopathological characteristics of CRC patients and the methylation patterns as a prognostic biomarker. 58 histopathologically confirmed cases of CRC were included in the study. Methylation status of IGFBP-3 gene promoter was determined by using methylation specific PCR (MS-PCR) and bisulfite sequencing. Kaplan–Meier survival curve and univariate cox regression analysis were used for survival analysis; Chi-square test used for association analysis. IGFBP3 promoter methylation was found in 37 (63.8%) out of 58 CRC cases. This promoter methylation status was significantly associated with lymph-node metastasis (P = 0.013) and the survival period. In stage II CRC cases, unmethylated gene promoter status showed better survival than the methylated. Mean overall survival (OS) of methylated and unmethylated group was 22.23 months, and 49.15 months respectively (P = 0.045), HR = 6.432, 95% CI 0.986–41.943. The IGFBP-3 promoter methylations found in 63.8% CRC cases in this study. The methylations was found to be associated with lymph-node metastasis and overall survival of the patients particularly in stage II CRC patients. However, promoter methylation was not associated with other clinocopathological characteristics such as age, gender, tumor location etc. Keywords Colorectal carcinoma · IGFBP-3 gene · Promoter methylation · Methylation specific PCR
Introduction Colorectal Carcinoma (CRC) remains a big human health problem with higher incidence rate and contributes 8.2% cancer associated deaths in 2018 globally [1]. In India, it is recorded as fourth most common cancer in males and fifth most in females with 6.4%, and 3.4% incidence rates respectively [1]. Even with the development of several diagnostic, prognostic approaches and therapies for CRC, existing * Sunil Babu Gosipatala [email protected]; [email protected] 1
Department of Biotechnology, School for Bio‑Science and Biotechnology, Babasaheb Bhimrao Ambedkar University, Lucknow 226025, India
2
Department of Pathology, Dr. Ram Manohar Lohia Institute of Medical Sciences, Lucknow 226010, India
3
Department of Surgical Gastroenterology, Dr. Ram Manohar Lohia Institute of Medical Science, Lucknow 226010, India
treatments do not effectively improve the chances of curability. Prognostic markers, which c
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