Research Paper Volume 12, Issue 1 pp 784—807

CCL14 is a prognostic biomarker and correlates with immune infiltrates in hepatocellular carcinoma

Yurong Gu 1, *, , Xiangyong Li 1, *, , Yanhua Bi 2, *, , Yubao Zheng 1, , Jialiang Wang 2, , Xiaoyan Li 1, , Zexuan Huang 2, , Lubiao Chen 1, , Yanlin Huang 1, , Yuehua Huang 1, 2, ,

  • 1 Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
  • 2 Guangdong Provincial Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
* Co-first authors

received: September 10, 2019 ; accepted: December 24, 2019 ; published: January 12, 2020 ;

https://doi.org/10.18632/aging.102656
How to Cite

Copyright © 2020 Gu et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

C-C motif chemokine ligand 14 (CCL14) is a chemokine promoting the activation of immune cells. However, the relationship between CCL14 expression, tumor immunity, and prognosis in Hepatocellular Carcinoma (HCC) remain unclear. CCL14 expression and its influence on tumor prognosis were analyzed by the ONCOMINE, Tumor Immune Estimation Resource (TIMER) and Kaplan-Meier plotter. The relationship between CCL14 expression and tumor immunity were analyzed by TIMER and Gene Expression Profiling Interactive Analysis (GEPIA). CCL14 expression was significantly lower in several human cancers, including HCC, than in corresponding normal tissues. CCL14 expression in HCC tissues correlated with prognosis. Low CCL14 expression associated with poorer overall survival, disease-specific survival, progression-free survival, and relapse-free survival in multiple cohorts of HCC patients, particularly at early disease stages (stage 1+2 or grade 2). CCL14 showed strong correlation with tumor-infiltrating B cells, CD4+ and CD8+ T cells, macrophages, neutrophils, and dendritic cells. CCL14 expression in HCC negatively correlated with expression of several immune cell markers, including exhausted T cell markers, PD-1, TIM-3 and CTLA-4, suggesting its role in regulating tumor immunity. These findings demonstrate that CCL14 is a potential prognostic biomarker that determines cancer progression and correlated with tumor immune cells infiltration in HCC.

Abbreviations

CCL14: C-C motif chemokine ligand 14; HCC: Hepatocellular Carcinoma; TIMER: Tumor Immune Estimation Resource; GEPIA: Gene Expression Profiling Interactive Analysis; OS: overall survival; DSS: disease-specific survival; PFS: progression-free survival; RFS: relapse-free survival; RFS: relapse-free survival; DSS: disease-specific survival; DMFS: distant metastasis-free survival; PPS: post progression survival; FP: first progression; TAMs: tumor-associated macrophages; NK cell: natural killer cells; Th cell: T helper cells; Tfh cell: follicular helper T; Tregs: regulatory T cells; PD-1: programmed death-1; CTLA-4: Cytotoxic T - Lymphocyte Antigen 4; TIM-3: T-cell immunoglobulin and mucin-domain containing-3.