title: CXCL17 expression predicts poor prognosis and correlates with adverse immune infiltration in hepatocellular carcinoma.
abstract: CXC ligand 17 (CXCL17) is a novel CXC chemokine whose clinical significance remains largely unknown. In the present study, we characterized the prognostic value of CXCL17 in patients with hepatocellular carcinoma (HCC) and evaluated the association of CXCL17 with immune infiltration. We examined CXCL17 expression in 227 HCC tissue specimens by immunohistochemical staining, and correlated CXCL17 expression patterns with clinicopathological features, prognosis, and immune infiltrate density (CD4 T cells, CD8 T cells, B cells, natural killer cells, neutrophils, macrophages). Kaplan-Meier survival analysis showed that both increased intratumoral CXCL17 (P = 0.015 for overall survival [OS], P = 0.003 for recurrence-free survival [RFS]) and peritumoral CXCL17 (P = 0.002 for OS, P<0.001 for RFS) were associated with shorter OS and RFS. Patients in the CXCL17low group had significantly lower 5-year recurrence rate compared with patients in the CXCL17high group (peritumoral: 53.1% vs. 77.7%, P<0.001, intratumoral: 58.6% vs. 73.0%, P = 0.001, respectively). Multivariate Cox proportional hazards analysis identified peritumoral CXCL17 as an independent prognostic factor for both OS (hazard ratio [HR] = 2.066, 95% confidence interval [CI] = 1.296-3.292, P = 0.002) and RFS (HR = 1.844, 95% CI = 1.218-2.793, P = 0.004). Moreover, CXCL17 expression was associated with more CD68 and less CD4 cell infiltration (both P<0.05). The combination of CXCL17 density and immune infiltration could be used to further classify patients into subsets with different prognosis for RFS. Our results provide the first evidence that tumor-infiltrating CXCL17+ cell density is an independent prognostic factor that predicts both OS and RFS in HCC. CXCL17 production correlated with adverse immune infiltration and might be an important target for anti-HCC therapies.
authors.affiliation: Department of Hepatic and Pancreatic Surgery, The First People's Hospital of Foshan, Foshan, Guangdong, P. R. China; State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, P. R. China.
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.affiliation: State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, P. R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Yan
authors.affiliation: State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, P. R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Xu
authors.affiliation: State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, P. R. China.
authors.forename: Chao-Qun
authors.initials: CQ
authors.lastname: Liu
authors.affiliation: Department of Hepatic and Pancreatic Surgery, The First People's Hospital of Foshan, Foshan, Guangdong, P. R. China.
authors.forename: Zuo-Jun
authors.initials: ZJ
authors.lastname: Zhen
authors.affiliation: Department of Hepatic and Pancreatic Surgery, The First People's Hospital of Foshan, Foshan, Guangdong, P. R. China.
authors.forename: Huan-Wei
authors.initials: HW
authors.lastname: Chen
authors.affiliation: Department of Hepatic and Pancreatic Surgery, The First People's Hospital of Foshan, Foshan, Guangdong, P. R. China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Ji
authors.affiliation: Department of Hepatic and Pancreatic Surgery, The First People's Hospital of Foshan, Foshan, Guangdong, P. R. China.
authors.forename: Zhi-Peng
authors.initials: ZP
authors.lastname: Wu
authors.affiliation: Department of Hepatic and Pancreatic Surgery, The First People's Hospital of Foshan, Foshan, Guangdong, P. R. China.
authors.forename: Jian-Yuan
authors.initials: JY
authors.lastname: Hu
authors.affiliation: State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, P. R. China.
authors.forename: Limin
authors.initials: L
authors.lastname: Zheng
authors.affiliation: Department of Hepatic and Pancreatic Surgery, The First People's Hospital of Foshan, Foshan, Guangdong, P. R. China; Faculty of Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong SAR, P. R. China.
authors.forename: Wan Yee
authors.initials: WY
authors.lastname: Lau
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000276:immunology* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D018925:Chemokines / Q000235:genetics* / Q000378:metabolism; D019743:Chemokines, CXC; D005260:Female; D005500:Follow-Up Studies; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000235:genetics* / Q000276:immunology* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D011379:Prognosis; D012307:Risk Factors; D016019:Survival Analysis; D047368:Tumor Burden; D055815:Young Adult
chemical_list: C508524:CXCL17 protein, human; D018925:Chemokines; D019743:Chemokines, CXC