Suppressed Expression of CXCL14 in Hepatocellular Carcinoma Tissues and Its Reduction in the Advanced Stage of Chronic HBV Infection

Yong Lin,1,2,* Bo-Mei Chen,3,* Xiao-Lu Yu,1,* Huo-Chun Yi,1 Jian-Jun Niu,1,2 Shu-Lian Li4 1Center of Clinical Laboratory, Zhongshan Hospital, School of Medicine, Xiamen University, Xiamen 361004, People’s Republic of China; 2Institution of Infectious Diseases, School of Medicine, Xiamen University, Xiamen 361004, People’s Republic of China; 3Department of Human Resources, Zhongshan Hospital, School of Medicine, Xiamen University, Xiamen 361004, People’s Republic of China; 4Department of Gynecology, Xiamen Huli District Maternity and Child Care Hospital, Xiamen 361009, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jian-Jun NiuCenter of Clinical Laboratory, Zhongshan Hospital, School of Medicine, Xiamen University, Xiamen 361004, People’s Republic of ChinaEmail niujianjun62@163.comShu-Lian LiXiamen Huli District Maternity and Child Care Hospital, Xiamen 361009, People’s Republic of ChinaEmail shu_lian_li@163.comIntroduction: CXCL14 was a significantly under-expressed mRNA in hepatocellular carcinoma tissues according to our microarray analysis, as well as head and neck squamous cell carcinoma and cervical squamous cell carcinoma. CXCL14 was considered a tumor suppressor in some studies; however, its role in HBV infection has not been identified.Methods: CXCL14 mRNA expression was quantified from 20 male HCC patients, and the fold change in cancer tissues was calculated by comparisons with normal adjacent tissues. Overall, 212 patients with chronic HBV infection and 180 HBV-free controls were recruited to investigate the association between CXCL14 polymorphisms and HBV progression as well as liver function parameters. Serum CXCL14 levels were determined by enzyme-linked immunosorbent assay (ELISA), and comparisons were made between different HBV status and different CXCL14 genotypes.Results: The mRNA expression of CXCL14 was 0.33-fold in HCC tissues when compared with adjacent tissues. The frequencies of rs2237062 and rs2547, but not rs2237061, were significantly different between patients with mild hepatitis and moderate-to-severe hepatitis. Moreover, rs2237062 and rs2547 polymorphisms correlated with impaired liver function parameters. ELISA results suggested that HBV-free controls had the highest level of CXCL14, while mild hepatitis patients had low levels, and patients with moderate-to-severe hepatitis had the lowest level. GA+AA genotypes of rs2547 were associated with reduced levels of serum CXCL14 because it introduced a stop codon at residue 109.Conclusion: CXCL14 was significantly suppressed in HBV-related HCC tissues, and its polymorphisms were linked with advanced stage chronic HBV infection and impaired liver function.Keywords: CXCL14, HBV infection, disease progression, polymorphism