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

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.

内容要旨・審査要旨・論文本文の公開
本論文は，著者Batkhishig Munkhjargalの学位論文として提出され，学位審査・授与の対象となっている。

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