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GHSR DNA hypermethylation is a new epigenetic biomarker for gastric adenocarcinoma and beyond |
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| Authors: | Mohammad Amini Kobra Foroughi Fatemeh Talebi Hemat Aghagolzade Haji Fatemeh Kamali Pouria Jandaghi Jörg D Hoheisel Mehdi Manoochehri |
| Institution: | 1. School of Medicine, Shahroud University of Medical Sciences, Shahroud, Iran
Amini and Foroughi should be considered joint first author.;2. School of Medicine, Shahroud University of Medical Sciences, Shahroud, Iran;3. Department of Biochemistry, Faculty of Medicine, Babol University of Medical Sciences, Babol, Iran;4. Iran National Tumor Bank, Cancer Institute of Iran, Tehran, Iran;5. Department of Human Genetics, McGill University, Montreal, Quebec, Canada McGill University and Genome Quebec Innovation Centre, Montreal, Quebec, Canada;6. Division of Functional Genome Analysis (B070), German Cancer Research Center (DKFZ), Heidelberg, Germany |
| Abstract: | Aberrations of DNA methylation are early events in the development of tumors. In this study, we investigated the DNA methylation status of growth hormone secretagogue receptor (GHSR), a promising pan-cancer biomarker, in gastric cancer (GC). Initially, data sets from DNA methylation and gene expression studies available at Gene Expression Omnibus (GEO) were analyzed. Confirmation was done on primary tumor specimens and adjacent normal stomach tissue samples. Both analyses showed significant hypermethylation of GHSR. For further validation, The Cancer Genome Atlas data on stomach cancer was used. A receiver operating characteristic curve analysis yielded an area under the curve value of 0.85, corroborating its usefulness as a diagnostic marker. A genome-wide comethylation analysis revealed several correlated genes. CREB1 was found to act as an upstream regulator of this gene network. Furthermore, GHSR methylation was found to be a biomarker in several other tumor entities, namely cancers of the bladder, endometrium, esophagus, head and neck, liver, thyroid, kidney, and ovary. Our findings along with previous reports on other types of cancer suggest a high potential of GHSR gene methylation as a pan-cancer biomarker, which could be considered for liquid biopsy applications. |
| Keywords: | biomarker DNA methylation gastric cancer GHSR |