Abstract
As one of the members of the kinesin family, the role and potential mechanism of kinesin family member C1 (KIFC1) in the development of liver hepatocellular carcinoma (LIHC), especially in the immune infiltration, have not been fully elucidated. In this study, multiple databases and immunohistochemistry were employed to analyze the role and molecular mechanism including the immune infiltration of KIFC1 in LIHC. Generally, KIFC1 mRNA expression was overexpressed in LIHC tissues than normal tissues, and its protein was also highly expressed in the LIHC. KIFC1 mRNA expression was correlated with tumor grade and TNM staging, which was negatively correlated with overall survival and disease-free survival. Moreover, univariable and multivariate Cox analysis revealed that upregulated KIFC1 mRNA is an independent prognostic factor for LIHC. The KIFC1 promoter methylation level was negatively associated with KIFC1 mRNA expression and advanced stages and grade in LIHC. The different methylation sites of KIFC1 had a different effect on the prognosis of LIHC. Specifically, the KIFC1 mRNA expression level showed intense correlation with tumor immunity, such as tumor-infiltrating immune cells and immune scores as well as multiple immune-related genes. Moreover, KIFC1 co-expressed with some immune checkpoints and related to the responses to immune checkpoint blockade (ICB) and chemotherapies. Significant GO analysis showed that genes correlated with KIFC1 served as catalytic activity, acting on DNA, tubulin binding, histone binding, ATPase activity, and protein serine/threonine kinase activity. KEGG pathway analysis showed that these genes related to KIFC1 are mainly enriched in signal pathways such as cell cycle, spliceosome, pyrimidine metabolism, and RNA transport. Conclusively, KIFC1 was upregulated and displayed a prognostic value in LIHC. Moreover, KIFC1 may be involved in the LIHC progression partially through immune evasion and serve as a predictor of ICB therapies and chemotherapies.
Highlights
Primary liver cancer is one of the top 10 lethal tumors worldwide
The results indicated that the mRNA expression of kinesin family member C1 (KIFC1) in liver hepatocellular carcinoma (LIHC) was higher than in normal tissues (p < 0.001) (Figure 1A)
From analyzing the KIFC1 mRNA expression from GSE14520, GSE57957, GSE36376, and TCGA, it indicated that the KIFC1 mRNA expression was markedly higher in LIHC compared with its adjacent non-cancerous tissues or normal liver tissues (p < 0.001) (Figure 1C)
Summary
Primary liver cancer is one of the top 10 lethal tumors worldwide. China accounts for 55% of new liver cancer cases and related deaths every year (Torre et al, 2012). Patients often come to the hospital for treatment and diagnosis when they have symptoms in the late stage. At this time, the 5-year survival rate of patients with advanced LIHC is less than 5% due to the loss of active treatment opportunities or high recurrence and metastasis after treatment (Ziogas and Tsoulfas, 2017). The development and clinical application of various targeted drugs for LIHC such as sorafenib extend the survival of patients to a certain degree (Hu et al, 2021). It is necessary to develop novel and valuable biomarkers to help us for the accurate and early diagnosis of LIHC and find effective targets to further improve the therapeutic effect of liver cancer (Huang et al, 2017)
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