Affiliations: [a] The First Clinical Medical College, Nanjing Medical University, Nanjing, Jiangsu, China | [b] Department of Physiology, Nanjing Medical University, Nanjing, Jiangsu, China | [c] The Laboratory Center for Basic Medical Sciences, Nanjing Medical University, Nanjing, Jiangsu, China
Correspondence:
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Corresponding authors: Jun Du, Department of Physiology, Nanjing Medical University, 101 Longmian Avenue, Jiangning District, Nanjing, Jiangsu 211166, China. Tel./Fax: +86 25 8686 9437; E-mail: [email protected]. Yueyuan Wang, The Laboratory Center for Basic Medical Sciences, Nanjing Medical University, 101 Longmian Avenue, Jiangning District, Nanjing, Jiangsu 211166, China. Tel./Fax: +86 25 8686 9437; E-mail: [email protected].
Abstract: BACKGROUND: Liver hepatocellular carcinoma (LIHC) is one of the most malignancy over the world. Previous studies have proven that Molecules Interacting with CasL-Like 1 (MICALL1) participated in cellular trafficking cascades, while there has no study to explore the function and carcinogenic mechanism MICALL1 in LIHC. METHODS: We aimed to investigate the relationship between MICALL1 mRNA expression and LIHC using TCGA database. The expression of MICALL1 protein in clinic samples were examined by UALCAN database. Kaplan-Meier method was used for survival analysis. Logistic regression and Cox regression were performed to evaluate the prognostic significance of MICALL1. The MICALL1-binding protein were built by the STRING tool. Enrichment analysis by GO, KEGG and GSEA was used to explore possible function of MICALL1. The ssGSEA method was used to investigate the association between MICALL1 expression and the immune infiltration level in LIHC. RESULTS: The expression and prognostic value of different MICAL family members in LIHC were evaluated. The expression of MICALL1 was significantly increased at both the transcript and protein levels in LIHC tissues. Further, the LIHC patients with high MICALL1 levels showed a worse OS, DSS and PFI. Some clinicopathologic features were identified to be related to MICALL1 expression in LIHC included clinical T stage, pathologic stage, histologic grade and AFP concentration. Univariate and multivariate survival analysis showed that MICALL1 was an independent prognostic marker for OS and DSS. Further enrichment analysis revealed that the K-RAS, TNFα/NF-κB and inflammatory response were significantly enriched in the high MICALL1 expression group. Immune infiltration analysis showed that high MICALL1 expression was correlated with infiltration level of macrophage cells, Th2 cells and some other immune cell types, including TFH. CONCLUSIONS: MICALL1 expression was significantly associated with immune cell infiltration and may regarded as a promising prognostic biomarker for LIHC patients.
