肺多形癌手術検体を顕微鏡的に正常肺組織, 上皮成分, 肉腫様成分に区分けし, 網羅的なDNAメチル化解析を行い, 肺多形癌の発癌・形態分化にDNAメチル化による遺伝子発現の変化が関与していることが示唆された. また, 肺多形癌の発癌に関与するDNAメチル化部位が有意に影響する細胞内シグナル伝達経路を同定. また, 発癌に関与するDNAメチル化が起きている遺伝子領域のうち, 肉腫様成分の分化に関与し, リンパ節転移・リンパ管侵襲と相関関係にある5遺伝子, 再発・生存と相関関係にある３遺伝子を同定した.
Surgical specimens of lung pleomorphic carcinoma were microscopically divided into normal lung tissue, epithelial-like component, and sarcoma-like component, and subjected to comprehensive DNA methylation analysis. Comparative analysis of DNA methylation rates in each region suggested that changes in gene expression due to DNA methylation are involved in carcinogenesis and morphological differentiation of lung pleomorphic carcinoma. We identified several intracellular signaling pathways significantly affected by DNA methylation sites involved in carcinogenesis, including the FGF signaling pathway, the TGF-beta family, and WNT/Beta-catenin signaling. In addition, we identified five genes (THSD1, ZFYVE21, CDT1, LYPD1, BGLAP) correlated with lymph node metastasis and lymphatic invasion, and three genes (LOC101927151, NRN1L, PLCXD3) correlated with recurrence and survival from the DNA methylation regions involved in carcinogenesis and differentiation to sarcoma-like components.
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