Abstract
Objective:
The study was designed to analyze the expression of CSNK1D in hepatocellular carcinoma (HCC) and to investigate the relationship between the expression of CSNK1D and the prognosis of HCC patients.
Methods:
The CSNK1D and AFP expression levels in patients with hepatocellular carcinoma and their corresponding clinical data were downloaded from TCGA and sorted with a Perl program. CSNK1D and AFP expression differences in normal liver tissue and liver cancer were compared and analyzed, based on the online database HCMDB, the relationships between the expression levels of CSNK1D and AFP and the proliferation and metastases of hepatocellular carcinoma were explored. The immunohistochemical data obtained from the Human Protein Atlas Database further verified the differences in the expression levels of CSNK1D and AFP in liver tissues and liver cancer tissues. Through Kaplan-Meier survival analysis, the effects of CSNK1D and AFP expression levels on the prognosis of patients with hepatocellular carcinoma were investigated, and the influences of and patients' gender, age and grades of cancer cells, tumor size, the status of lymph node metastasis, distant metastasis, and tumor stage on the expression of CSNK1D were analyzed with R language. The influence of differential expressions of CSNK1D on survival time was compared and the prognostic factors influencing the survival of HCC patients were statistically explored by univariate and multivariate analyses. The potential influencing mechanism of CSNK1D on the prognosis of HCC was explored by GSEA enrichment.
Results:
The expression levels of CSNK1D and AFP in cancer foci were significantly higher than that in normal tissues, However, in the same patient, the expression levels of AFP in para-carcinoma tissues and cancer tissues showed no significant differences. The expression levels of CSNK1D in hepatocellular carcinomas with distant metastases were higher than that in those without metastasis, but the expression levels of AFP in metastatic hepatocellular carcinomas were lower than that in those hepatocellular carcinomas without metastases. In immunohistochemical tests, CSNK1D was moderately positive in normal liver tissues, slightly positive in normal bile duct tissues, and highly positive in hepatocellular carcinoma. AFP was slightly positive in normal liver tissues and negative in hepatocellular carcinoma, but it was not detected in normal intrahepatic bile duct tissue. Survival analyses results suggested that higher expression levels of CSNK1D corresponded to the shorter survival times, whereas the expression level of AFP showed no significant influence on survival time. The expression levels of CSNK1D were not correlated with gender, age, lymph node metastasis or distant metastasis The main factors influencing the expression levels of CSNK1D included tumor size, cancer cell grade and tumor stage. The expression levels of CSNK1D in T2 and T3 were higher than that in T1. The expression levels of CSNK1D in G3 and G4 were higher than that in G1. The expression levels of CSNK1D in Stage II and Stage III were higher than that in Stage I. Univariate analysis suggested that tumor size, cell grade, distant metastasis, clinical stage, and CSNK1D expression level were prognostic factors influencing the survival of patients. Multivariate analysis suggested that CSNK1D expression levels are an independent factor influencing the HCC prognosis. GSEA enrichment analysis indicated that CSNK1D mainly influenced the prognosis of HCC through cell cycle, WNT signaling pathway, amino acid degradation metabolism and other pathways.
Conclusion:
CSNK1D is an independent factor influencing HCC prognosis and has the potential to be developed as a potential therapeutic target for HCC, and better than AFP in predicting the prognosis of hepatocellular carcinoma.
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