title: Downregulation of ADAMTS8 by DNA Hypermethylation in Gastric Cancer and Its Clinical Significance.
abstract: A disintegrin and metallopeptidase with thrombospondin motif type 8 (ADAMTS8), a member of the ADAMTS family, was discovered as a novel angiogenesis inhibitor. We analyzed the expression and methylation of ADAMTS8 in primary gastric tumors and gastric cancer cell lines. We also examined the relationship between ADAMTS8 expression and methylation and clinicopathologic features. The results showed that the significant downregulation of ADAMTS8 mRNA expression was observed in gastric cancer cell lines and tissues, and its expression was related to invasive depth and lymph node metastasis. CpG was hypermethylated in gastric cancer cell lines MKN45, MGC803, and BGC823, as well as primary gastric cancer specimens. ADAMTS8 mRNA expression was significantly lower in methylated primary gastric tumors. A significant association was found between ADAMTS8 methylation status and lymph node metastasis in primary gastric cancer. Moreover, ADAMTS8 expression was upregulated in the gastric cancer cell lines MGC803, BGC823, and MKN45 after treatment with 5-aza-2'-deoxycytidine. Thus, our results demonstrate that expression of ADAMTS8 mRNA is significantly decreased and DNA methylation is frequent in gastric cancer. ADAMTS8 hypermethylation is associated with decreased expression in gastric cancer and may play an important role in the invasion and metastasis of gastric cancer.
authors: Department of Gastrointestinal Surgery, The Fourth Affiliated Hospital, China Medical University, No. 4 Chongshandong Road, Shenyang 110032, China.
authors: Jing
authors: 0000-0002-4238-4917
authors: J
authors: Chen
authors: Department of Gastrointestinal Surgery, The Fourth Affiliated Hospital, China Medical University, No. 4 Chongshandong Road, Shenyang 110032, China.
authors: Jiakui
authors: J
authors: Zhang
authors: Department of Gastrointestinal Surgery, The Fourth Affiliated Hospital, China Medical University, No. 4 Chongshandong Road, Shenyang 110032, China.
authors: Xin
authors: X
authors: Li
authors: Department of Gastrointestinal Surgery, The Fourth Affiliated Hospital, China Medical University, No. 4 Chongshandong Road, Shenyang 110032, China.
authors: Chundong
authors: C
authors: Zhang
authors: Department of Gastrointestinal Surgery, The Fourth Affiliated Hospital, China Medical University, No. 4 Chongshandong Road, Shenyang 110032, China.
authors: Hongbin
authors: H
authors: Zhang
authors: Department of Gastrointestinal Surgery, The Fourth Affiliated Hospital, China Medical University, No. 4 Chongshandong Road, Shenyang 110032, China.
authors: Junzhe
authors: J
authors: Jin
authors: Department of Gastrointestinal Surgery, The Fourth Affiliated Hospital, China Medical University, No. 4 Chongshandong Road, Shenyang 110032, China.
authors: Dongqiu
authors: D
authors: Dai
mesh_terms: D000071096:ADAMTS Proteins / Q000235:genetics* / Q000378:metabolism; D000368:Aged; D001374:Azacitidine / Q000494:pharmacology; D045744:Cell Line, Tumor; D019175:DNA Methylation / Q000187:drug effects / Q000235:genetics*; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: D012333:RNA, Messenger; D000071096:ADAMTS Proteins; C120807:ADAMTS8 protein, human; D001374:Azacitidine