Promoter hypermethylation regulates vitamin D receptor (VDR) expression in colorectal cancer-A study from Kashmir valley
| Autor: | Bushra Nissar, Bashir A. Ganai, Falaque ul Afshan, Akbar Masood, Niyaz Ahmad Naykoo, Nisar A. Chowdri, Misbah Majid |
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| Rok vydání: | 2021 |
| Předmět: |
Male
Cancer Research Colorectal cancer India Biology Retinoid X receptor Calcitriol receptor Cohort Studies 03 medical and health sciences 0302 clinical medicine Vitamin D Response Element Genetics Vitamin D and neurology medicine Humans Epigenetics Promoter Regions Genetic Molecular Biology Transcription factor DNA Methylation Middle Aged Prognosis medicine.disease Survival Rate 030220 oncology & carcinogenesis DNA methylation Cancer research Receptors Calcitriol Female Colorectal Neoplasms |
| Zdroj: | Cancer Genetics. :96-106 |
| ISSN: | 2210-7762 |
| DOI: | 10.1016/j.cancergen.2021.01.002 |
| Popis: | Colorectal carcinogenesis (CRC) is a multistep process, involving both genetic and epigenetic modifications of genes involved in diverse pathways ranging from tumor suppression to DNA mismatch repair.This study was undertaken to assess the role of promoter methylation of vitamin D receptor (VDR) gene, a transcription factor with myriad biological functions, in relation to its expression and clinicopathological parameters.Tissue specimens were taken from a total of 75 colorectal cancer cases paired with their normal surrounding epithelium and analyzed by Real-time RT-PCR for assessing the expression profile and MS-PCR for analyzing the promoter methylation status of the VDR gene. Blood sample from the same patients was drawn for vitamin D estimation.The frequency of promoter methylation in cancerous tissue was 37.33% against 9.33% in normal tissues (p0.001). The hypermethylated status of VDR promoter showed significantly inverse association with its expression (p=0.008). Furthermore, when compared with the clinical parameters, methylation status of VDR promoter was significantly associated with tumor staging (p=0.008), grading (p0.001), depth of invasion (p=0.002) and lymph node metastases (p0.001). Univariate and multivariate analysis indicated patients with increased VDR expression (p0.001) and decreased methylation status (p=0.012) exhibited longer overall survival. Additionally, serum 25(OH)DOur study, first of its kind from Kashmir, indicated that VDR shows aberrant methylation pattern in CRC with consequent loss in its expression. |
| Databáze: | OpenAIRE |
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