Chemokine CCL14 is a potential biomarker associated with immune cell infiltration in lung adenocarcinoma

Abstract

Abstract Objective: C-C motif chemokine ligand 14 (CCL14) is constitutively expressed in tissues. We aimed to investigate the relationship between CCL14 and tumor-infiltrating immune cells (TIICs), and explore the prognostic role in LUAD. Materials and methods: Oncomine and TCGA databases were analyzed to examine the expression of CCL14 in LUAD. Kaplan-Meier plotter and Gene Expression Profiling Interactive Analysis (GEPIA, version 2) were conducted to evaluate the prognostic value in LUAD. Tumor Immune Estimation Resource (TIMER) and GEPIA2 were used to explore the relationship between CCL14 and TIICs. Gene functional enrichment was performed by Gene Set Enrichment Analysis (GSEA). The expression and function of CCL14 were investigated in vitro. miR-CCL14 overexpression vector plasmids were transfected into cells. Cell proliferation, migration and invasion assays were conducted to explore CCL14 biological function in LUAD cell lines. Results: Low-expression level of CCL14 was associated with poor-prognosis in LUAD. In vitro, the mRNA expression of CCL14 in lung epithelial cells was statistically higher than in LUAD cell lines. Upregulating the expression of CCL14 suppressed cell proliferative, migratory and invasive abilities. Immune infiltration analysis displayed there were positive correlations between CCL14 expression and TIICs (including CD8+ T cells, CD4+ T cells, B cells, neutrophils, etc.). Markers of TIICs exhibited different CCL14-related immune infiltration patterns. GSEA analysis showed that the low-expression of CCL14 was related to histone deacetylases (HDACs), G2/M checkpoints and Notch signaling pathways. Conclusions: CCL14 may be an anti-oncogene by regulating TIICs and is expected to become a potential prognostic indicator and therapeutic target in LUAD.