Aberrant methylation of dipeptidyl peptidase‑like 6 as a potential prognostic biomarker for lung adenocarcinoma

Munkhjargal,Batkhishig; Kondo,Kazuya; Soejima,Shiho; Tegshee,Bilguun; Takai,Chikako; Kawakita,Naoya; Toba,Hiroaki; Takizawa,Hiromitsu

doi:10.3892/ol.2023.13792

Aberrant methylation of dipeptidyl peptidase‑like 6 as a potential prognostic biomarker for lung adenocarcinoma

Authors:
- Batkhishig Munkhjargal
- Kazuya Kondo
- Shiho Soejima
- Bilguun Tegshee
- Chikako Takai
- Naoya Kawakita
- Hiroaki Toba
- Hiromitsu Takizawa
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Affiliations: Department of Oncological Medical Services, Graduate School of Biomedical Sciences, Tokushima University, Tokushima 770‑8509, Japan, Department of Medicine, Division of Cancer Biology, Case Western Reserve University at MetroHealth Medical Center, Cleveland, OH 44109, USA, Department of Thoracic, Endocrine Surgery and Oncology, Graduate School of Biomedical Sciences, Tokushima University, Tokushima 770‑8503, Japan
Published online on: April 5, 2023 https://doi.org/10.3892/ol.2023.13792
Article Number: 206
Copyright: © Munkhjargal et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

We previously performed the genome‑wide screening of aberrantly methylated CpG islands (CGIs) using the paired tumorous and non‑tumorous tissues of 12 lung adenocarcinomas (LADC). In comparisons with paired normal lung tissues, dipeptidyl peptidase‑like 6 (DPP6) has been identified as the most significantly hypermethylated CGI in LADC. DPP6 is a protein that modulates A‑type potassium channels in the somatodendritic compartments of neurons, which play a role in synaptic plasticity. Previous studies have showed that DPP6 is downregulated in cancers, such as acute myeloid leukemia and melanoma, but upregulated in colon cancer, which is attributed to hyper‑ and hypomethylation, respectively. The present study investigated the methylation and expression levels of DPP6 and its prognostic value in patients with LADC. The DNA methylation and mRNA expression levels of DPP6 in surgically resected LADC tissues were examined by bisulfite pyrosequencing and reverse transcription‑quantitative PCR, respectively. The DNA methylation and mRNA expression levels of DPP6 were both significantly higher in LADC tissues compared with in normal lung tissues (n=25; P<0.0001). Overall and disease‑free survival rates were significantly higher in LADC with high mRNA expression levels compared with those with low levels. In conclusion, epigenetic alterations in DPP6 were significantly higher in LADC tissues compared with in normal lung tissues, which may contribute to the malignant features and worse prognosis of these patients.

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