title: Abnormal hypermethylation of promoter region downregulates chemokine CXC ligand 14 expression in gastric cancer.
abstract: CXCL14, a new member of the CXC subfamily of chemokines, is differentially expressed in several types of tumors. The expression of CXCL14 and its clinical significance in gastric cancer are unclear to date. In this study, the expression of CXCL14 was detected by quantitative PCR and immunohistochemistry assay. DNA methylation was analyzed by bisulfite sequencing PCR. Student's t-test and Kruskal-Wallis H test were used to evaluate the differences of the CXCL14 expression between the groups. Kaplan-Meier survival curve and Cox regression model were used to evaluate the clinical significance of CXCL14 expression in gastric cancer. Data indicated that the levels of CXCL14 mRNA declined (P<0.001) in gastric carcinoma tissues compared to the paired normal tissues. Immunohistochemical analysis also showed the decrease of CXCL14 protein in the tumor tissue (P<0.001). Analysis of CpG islands methylation in CXCL14 promoter region and first exon area indicated that the abnormal hypermethylation of promoter region in tumor tissue is one of the mechanisms causing the reduction. When gastric cancer cells were demethylated with 5-Aza-2'-deoxycytidine, CXCL14 expression was restored. Downregulation of CXCL14 was associated with the depth of penetration (P<0.001) and positively correlated with prognosis in stage III/IV (P=0.046). In conclusion, it is possible that CXCL14 is involved in the development and progression of gastric cancer. Hypermethylation in the promoter is one of the reasons that CXCL14 has lower expression in gastric adenocarcinoma tissues. The level of CXCL14 expression may be a valuable adjuvant parameter in predicting the prognosis of gastric cancer patients and, thus, a potential therapeutic target.
authors: Department of General Surgery, The First Affiliated Hospital of Wenzhou Medical University, Ouhai District, Wenzhou, Zhejiang 325035, P.R. China.
authors: Changyuan
authors: C
authors: Hu
authors: Feng
authors: F
authors: Lin
authors: Guangbao
authors: G
authors: Zhu
authors: Xiangyang
authors: X
authors: Xue
authors: Yujie
authors: Y
authors: Ding
authors: Zhiguang
authors: Z
authors: Zhao
authors: Lifang
authors: L
authors: Zhang
authors: Xian
authors: X
authors: Shen
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism / Q000401:mortality; D000328:Adult; D015153:Blotting, Western; D019743:Chemokines, CXC / Q000235:genetics* / Q000378:metabolism; D015331:Cohort Studies; D019175:DNA Methylation; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013270:Stomach / Q000473:pathology; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000401:mortality; D015996:Survival Rate
chemical_list: C118056:CXCL14 protein, human; D019743:Chemokines, CXC; D012333:RNA, Messenger