Aberrant expression of DUSP4 is a specific phenomenon in betel quid-related oral cancer

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ORIGINAL PAPER

Aberrant expression of DUSP4 is a specific phenomenon in betel quid‑related oral cancer Bhoj Raj Adhikari1 · Koki Yoshida1 · Durga Paudel1 · Tetsuro Morikawa1 · Osamu Uehara2 · Jun Sato1 · Malsantha Muthumala3 · Prasad Amaratunga4 · Toshiya Arakawa5 · Itsuo Chiba2 · Yoshihiro Abiko1  Received: 12 July 2020 / Accepted: 8 September 2020 © The Japanese Society for Clinical Molecular Morphology 2020

Abstract Oral cancer due to betel quid chewing habit is very common in South Asian countries. We attempted to detect the presence of a novel gene in epithelial cells stimulated with arecoline, a main component of betel quid. Human gingival epithelial progenitors were cultured and treated with a 3-day alternating regimen with/without 50 μg/ml arecoline for 1 month. DNA microarray and methylation arrays were analyzed to identify the candidate genes. Immunohistochemical staining was performed in the tissue samples. Genome-wide analyses, quantitative reverse transcription PCR and quantitative methylation-specific PCR revealed DUSP4 as the most significant and promising gene. The methylation levels of DUSP4 were significantly higher in the betel quid-related oral squamous cell carcinoma (OSCC) than those in the non-related OSCC and controls (Mann– Whitney U test, p