Increased S100A15 expression and decreased DNA methylation of its gene promoter are involved in high metastasis potential and poor outcome of lung adenocarcinoma

被引：12

作者：

Chen, Yung-Che ^{[1
,6
]}

Lin, Meng-Chih ^{[1
,6
]}

Hsiao, Chang-Chun ^{[6
,7
]}

Zheng, Yi-Xin ^{[1
]}

Chen, Kuang-Den ^{[2
]}

Sung, Ming-Tse ^{[3
]}

Chen, Chung-Jen ^{[4
]}

Wang, Ting-Ya ^{[1
]}

Lin, Yong-Yong ^{[1
]}

Chang, Huang-Chih ^{[1
,6
]}

Chen, Yu-Mu ^{[1
]}

Chang, Jen-Chieh ^{[5
]}

机构：

[1] Chang Gung Univ, Coll Med, Kaohsiung Chang Gung Mem Hosp, Div Pulm & Crit Care Med, Kaohsiung, Taiwan

[2] Chang Gung Univ, Coll Med, Kaohsiung Chang Gung Mem Hosp, Ctr Translat Res Biomed Sci, Kaohsiung, Taiwan

[3] Chang Gung Univ, Coll Med, Kaohsiung Chang Gung Mem Hosp, Dept Pathol, Kaohsiung, Taiwan

[4] Chang Gung Univ, Coll Med, Kaohsiung Chang Gung Mem Hosp, Div Rheumatol, Kaohsiung, Taiwan

[5] Chang Gung Univ, Coll Med, Kaohsiung Chang Gung Mem Hosp, Dept Med Res, Kaohsiung, Taiwan

[6] Chang Gung Univ, Coll Med, Kaohsiung Chang Gung Mem Hosp, Grad Inst Clin Med Sci, Kaohsiung, Taiwan

[7] Kaohsiung Chang Gung Mem Hosp, Ctr Shockwave Med & Tissue Engn, Kaohsiung, Taiwan

来源：

ONCOTARGET | 2017年 / 8卷 / 28期

关键词：

lung adenocarcinoma; S100A15; DNA methylation; next generation sequencing; SQUAMOUS-CELL CARCINOMA; HYPOMETHYLATION-INDUCED EXPRESSION; BREAST-CANCER; PSORIASIN S100A7; WIDE ANALYSIS; DIFFERENTIATION; KNOCKDOWN; INVASIVENESS; BIOMARKERS; PROTEINS;

D O I：

10.18632/oncotarget.17391

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Purpose: This study aims to determine the functional role of S100A15 and its promoter DNA methylation patterns in lung cancer progression. Experimental Design: We analyzed 178 formalin-fixed paraffin embedded specimens from lung cancer patients, including 24 early stage and 91 advanced stage adenocarcinoma. S100A15 protein expression was evaluated by immunohistochemistry stain, and its DNA methylation levels were measured by pyrosequencing. Results: S100A15 nuclear staining was increased in lung adenocarcinoma patients with distant metastasis versus those without distant metastasis. There was reduced one/three-year overall survival in adenocarcinoma patients receiving first line target therapy and harboring high nuclear expressions of S100A15. Both DNA methylation levels over -423 and -248 CpG sites of the S100A15 gene promoter were decreased in adenocarcinoma patients with distant metastasis, and the former was associated with lower one-year overall survival. The highly invasive CL1-5 cell lines display decreased DNA methylation over -412/-248/-56 CpG sites of the S100A15 gene promoter and increased S100A15 gene/protein expressions as compared with the less invasive CL1-0 cell lines. Knockdown of S100A15 in CL1-5 cell line inhibited cell proliferation, migration, and invasion, while over-expression of S100A15 in CL1-0 cell line promoted cell proliferation, migration, and invasion. RNA sequencing analysis revealed potential biological effects of S100A15 over-expression and knock-down with CTNNB1, ZEB1, CDC42, HSP90AA1, BST2, and PCNA being the pivotal down-stream mediators. Conclusions: Increased S100A15 expression and decreased DNA methylation of its gene promoter region were associated with high metastasis potential and poor outcome in lung adenocarcinoma, probably through triggering CTNNB1 -centered pathways.

引用

页码：45710 / 45724

页数：15