Identification and Validation of the lncRNA BACE1-AS as Immune-Related Influencing Factor in Tumorigenesis following Pan-Carcinoma Analysis

Abstract

Background. The lncRNA BACE1-AS was identified as a plasma molecular marker in the early diagnosis of Alzheimer's disease, but its role in tumors remains poorly defined. Methods. The expression patterns, genomic mutation, and prognostic significance of BACE1-AS in pan-cancers were compared by analyzing 32 types of tumors from The Cancer Genome Atlas and cBioPortal databases. The relationships between BACE1-AS expression levels and the degree of immune cell infiltration, immune components, and immune-related genes were explored. The possible molecular mechanisms of BACE1-AS in tumors were explored using gene set enrichment analysis (GSEA). Finally, the role of BACE1-AS in hepatocellular carcinoma was confirmed via quantitative real-time polymerase chain reaction (qRT-PCR). Results. BACE1-AS expression levels were significantly upregulated in LIHC, GBM, KIRC, CHOL, STAD, KICH, COAD, and PRAD. Higher expression levels of BACE1-AS were associated with worse overall survival in patients with HNSC and LIHC, while the opposite was found in PCPG and THCA. The overall mutation rate of BACE1-AS in pan-cancer was only approximately 0.9%, and it occurred mainly in uveal melanoma and uterine carcinoma. Generally, BACE1-AS expression was negatively correlated with the immune microenvironment. BACE1-AS expression was mainly related to naïve B cells, activated memory CD4 T cells, monocytes, M1 macrophages, M2 macrophages, and resting mast cells. The potential mechanisms of BACE1-AS in tumors were mainly via regulating the activities of B cell-mediated immunity, immune response regulating cell surface receptor signaling, RNA binding in posttranscriptional gene silencing, B cell receptor signaling pathways, and immune receptor activity. Finally, the qRT-PCR results confirmed that the expression levels of BACE1-AS in hepatocellular carcinoma cell lines were upregulated. Conclusions. Overall, our results suggest that BACE1-AS is associated with the expression, prognosis, and rate of immune cell infiltration of most tumors. Thus, BACE1-AS may be a potential target for immunotherapies aimed at improving cancer patient outcomes.