QU Cai-hao, MA Teng-da, WANG Rui, LI Xiao-mei, LI Yu-min
Life Science Research.
Abstract: Brain-specific angiogenesis inhibitor 1-associated protein 2-like 2 (BAIAP2L2) is an epithelial-specific BAR domain protein. It was recently reported that BAIAP2L2 was overexpressed in multiple cancer tissues, but its roles in liver cancer are still poorly understood. To provide theoretical basis for BAIAP2L2 as a new liver cancer biomarker, this study explored the expression level of BAIAP2L2 in liver cancer and its biological significance and potential clinical application value through bioinformatics methods. Firstly, mRNA-seq, miRNA-seq, DNA methylation data and corresponding clinicopathologic information of liver cancer pa-tients were downloaded from the TCGA and ICGC databases, and protein expression data were obtained from the HPA database. The expression levels of BAIAP2L2 in cancer and adjacent tissues were compared, and the relationship between the expression of BAIAP2L2 and the clinicopathological characteristics of liver cancer was analyzed. Subsequently, the receiver operating characteristic (ROC) curve was used to evaluate the performance of BAIAP2L2 expression in the diagnosis of liver cancer. The survival curves were drawn to compare the differences in groups of patients with different expression levels of BAIAP2L2, and Cox regres-sion analysis was used to calculate the hazard ratio (HR). Finally, the potential regulatory factors for BAIAP2L2 were predicted in the miRWalk database. The TIMER database was used to explore the correlation between BAIAP2L2 expression and infiltrated immune cells in liver cancer tissues. Gene set enrichment analysis (GSEA) was performed to identify BAIAP2L2 involved functional pathways. The results showed that the expres-sion level of BAIAP2L2 in liver cancer tissues was significantly higher than that in adjacent tissues (P<0.001), and BAIAP2L2 had a good diagnostic value for liver cancer (AUC=0.891, P<0.001). Its expression level was significantly correlated with the gender, T stage, alpha fetoprotein (AFP), clinical stage and survival status in liver cancer patients (P<0.05). Patients with high expression of BAIAP2L2 showed a worse prognosis outcome (P<0.05), and BAIAP2L2 was an independent risk factor for prognosis of patients with liver cancer (HR: 1.522, 95% CI: 1.044~2.219, P<0.05). There was a significant negative correlation between BAIAP2L2 methylation and BAIAP2L2 expression (P<0.001), and patients with hypomethylation had a worse prognosis (P<0.05). hsa-miR-99a-3p was identified as one of the factors that can regulate the expression of BAIAP2L2. The expression of BAIAP2L2 was significantly correlated with the infiltration levels of B cells, CD4+ T cells, CD8+ T cells, macrophages, neutrophils and dendritic cells in liver cancer tissues (P<0.05). GSEA showed that BAIAP2L2 was involved in the following pathways: regulation of cell cycle, p53 signaling pathway, homologous recombi-nation, etc. In conclusion, BAIAP2L2 is highly expressed in liver cancer due to a variety of complex mecha-nisms and can be used as a potential biomarker for diagnosis and prognosis of liver cancer.