CC趋化因子配体20在肝细胞癌组织中的表达及其在肝细胞肝癌预后评估中作用的生物信息学分析

doi:10.13481/j.1671-587X.20220422

Abstract

Abstract: Objective

To investigate the expression of CC chemokine ligand 20 （CCL20） in liver hepatocellular carcinoma（LIHC） tissue and explore its influence in the prognosis in the patients with LIHC， and to elucidate the mechanism of CCL20 affecting the malignant behavior of LIHC. Methods The mRNA expression levels and clinical data in cancer tissue and para-cancer tissue of the LIHC patients were obtained from The Cancer Genome Atlas （TCGA） and UCSC Xena platforms using Rstudio （4.03） software， and the differences in the CCL20 mRNA expression between the two kinds of tissues were compared，and these results were validated using GEPIA combined with GTEx data. Kaplan-Meier survival analysis and Cox regression analysis methods were used to analyze the relationship between the CCL20 mRNA expression level and the prognosis of LIHC patients. The correlation between the CCL20 expression level and alpha fetoprotein （AFP） level in the LIHC patients was analyzed by Pearson correlation analysis， and the area under receiver operating characteristic （ROC） curve（AUC）， Nomogram and correction curve were used to analyze the correlations between the CCL20 mRNA expression level and the clinical diagnosis and survival prediction in the patients with LIHC. GSEA enrichment analysis of the CCL20 mRNA correlation between the expression level expression in cancer tissue of the LIHC patients was performed using the TCGA database， and the correlation between the expression level of CCL20 mRNA and DNA copy-number alterations（CNA） and DNA methylation level were analyzed.

Results

Compared with para-cancer tissue，the CCL20 mRNA expression level in cancer tissue of the LIHC patients was significantly increased（P<0.01）.The Kaplan-Meier survival analysis results showed that the patients with low expression of CCL20 mRNA had a significantly better prognosis than those with high expression of CCL20 mRNA （HR=1.789， P<0.01）. The Cox univariate and multifactorial regression analysis results showed that the CCL20 mRNA expression level was an independent prognostic factor of the LIHC patients（P<0.05）； the Pearson correlation analysis showed a positive correlation between the CCL20 mRNA expression levels and AFP levels in cancer tissue of the LIHC patients （P<0.01）. The CCL20 mRNA expression level had certain reference value in assessment of clinical diagnosis of the LIHC patients（AUC=0.69，P<0.01）， and could effectively predict the survival rate of the LIHC patients. The GSEA analysis showed that CCL20 could be involved in LIHC cell adhesion， cytokine-cytokine receptor interaction and ribosome function implementation through chemokine， NOD-like receptor（NLR）， PPAR and Toll-like receptor（TLR） tumor-related signaling pathways. The genetic and epigenetic analysis showed that compared with normal diploid sample group， the expression levels of CCL20 mRNA in copy number loss group and copy number amplification group had no significant differences（P>0.05）；compared with copy number loss group，the CCL20 mRNA expression level in copy number amplification group was significantly increased（P<0.05）；the expression level of CCL20 mRNA was negatively correlated with its DNA methylation level （cor=－0.11，P<0.05）.

Conclusion

The CCL20 expression upregulation in LIHC tissue is significantly associated with the poor prognosis of LIHC patients， which can be involved in the malignant process of LIHC through multiple signaling pathways， and it can be used as one of the indicators for prognostic assessment and prediction of survival of the LIHC patients.

Key words: CC chemokine ligand 20, Liver hepatocellular carcinoma, Bioinformatics analysis, Prognosis, Clinical diagnosis

CLC Number:

R735.7

Liantao HU,Wenjun DENG,Shizhen LU,Luo SUN,Xuebing LI,Chuhao LI,Xinran WANG,chunbing ZHANG,Yue LI,Weiqun WANG. Bioinformatics analysis on CC chemokine ligand 20 expression in hepatocellular carcinoma tissue and its effect on prognostic assessment of liver hepatocellular carcinoma[J].Journal of Jilin University(Medicine Edition), 2022, 48(4): 1010-1017.

Figures/Tables 6

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Tab. 1

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Variable	Univariate analysis		Multivariate analysis
Variable	HR (95% CI)	P	HR (95% CI)	P
Age (≥ 65 years old vs < 65 years old)	1.23(0.85－1.78)	0.273	－	－
Gender (Female vs Male)	1.26(0.87－1.84)	0.228	－	－
Family history of cancer (Yes vs No)	1.14(0.76－1.69)	0.530	－	－
TNM stage (Ⅱ vs Ⅰ)	1.42(0.87－2.32)	0.160	1.47(0.90－2.40)	0.123
TNM stage (Ⅲ vs Ⅰ)	2.72(1.78－4.15)	<0.001	2.76(1.80－4.23)	<0.001
TNM stage (Ⅳ vs Ⅰ)	5.44(1.68－17.63)	0.005	5.51(1.70－17.89)	0.004
Histologic grade (G3-G4 vs G1-G2)	1.14(0.78－1.67)	0.489	－	－
Ishak score (5－6 vs 0－4)	0.87(0.50－1.50)	0.612	－	－
Child-Pugh grade (B-C vs A)	1.66(0.82－3.36)	0.159	－	－
AFP(Positive vs Negative)	1.45(0.92－2.28)	0.108	－	－
Residual tumor (R1-R2 vs R0)	1.17(0.43－3.20)	0.754	－	－
CCL20 (High vs Low)	1.07(1.00－1.14)	0.045	1.07(1.01－1.14)	0.034

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Bioinformatics analysis on CC chemokine ligand 20 expression in hepatocellular carcinoma tissue and its effect on prognostic assessment of liver hepatocellular carcinoma

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