Prognostic value of LECT2 and relevance to immune infiltration in hepatocellular carcinoma

Abstract

Background: Previous studies have shown that Leukocyte cell-derived chemotaxin2 (LECT2) is associated with the development of HCC. However, there are still no studies with a comprehensive analysis of the role of LECT2 in hepatocellular carcinoma (HCC).Methods: TCGA data sets were used to analyze the expression of LECT2 in HCC. In addition, the prognostic value of LECT2 in HCC was also investigated. DriverDBv3 was used to analyze the Mutation, CNV, and methylation profiles of LECT2. And, validated by immunohistochemistry in 72 HCC samples. The prognostic value of LECT2 and the correlation with clinicopathological features were analyzed. The GO/KEGG enrichment analysis of LECT2 co-expression and gene set enrichment analysis (GSEA) was performed using the R software package. The PPI interaction network was constructed by Search Tool for the Retrieval of Interacting Genes (STRING) database. Immune infiltration was estimated by the XCELL, TIMER, QUANTISEQ, MCPCOUNTER, EPIC, CIBERSORT abs and CIBERSORT algorithms, and Spearman was used to analyzing their correlation with LECT2. Moreover, we analyzed the correlation of LECT2 expression with immune checkpoint molecules and HLA genes. Finally, we analyzed the IC50 values of six chemotherapeutic drugs by the pRRophetic package.Results: Reduced LECT2 expression levels found in HCC patients. Moreover, decreased levels of LECT2 were associated with poor overall survival, disease-free survival, disease-specific survival, and progression-free survival. Besides, methylation was significantly associated with LECT2 expression. The functional enrichment analysis revealed that LECT2 may affect HCC progression through various pathways such as JAK/STAT signaling pathway, cell cycle, and pathways in cancer. Additionally, the results showed that LECT2 expression was negatively correlated with immune infiltration of B cells, Neutrophil, Monocyte, Cancer-associated fibroblast, and Myeloid dendritic cell, and positively correlated with T cell CD8+ naive, Endothelial cell, and Hematopoietic stem cell. LECT2 expression was negatively correlated with multiple immune checkpoint molecules and HLA genes. Chemosensitivity analysis showed that chemosensitivity was lower in the LECT2 high expression group. We validated the prognostic value of LECT2 and analysis of clinicopathological features showed a lower TNM stage in the group with high expression of LECT2.Conclusion: Low expression of LECT2 in HCC is closely associated with poor prognosis, LECT2 may have potential clinical applications due to its unique immunological effects.