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

• Published in: Journal of Immunology Research Vol. 2021; pp. 1589864 - 21
• Main Authors: Wang, Mengmeng, Chen, Di, Xu, Yushuang, Qiu, Mengjun, Jiang, Xin, Xiong, Zhifan
• Format: Journal Article
• Language: English
• Published: Egypt Hindawi 08.12.2021; Hindawi Limited; Wiley
• Subjects: Adult; Aged; Alzheimer's disease; Apoptosis; B cells; Biomarkers, Tumor - metabolism; Cancer; Cancer therapies; Carcinogenesis - genetics; Carcinogenesis - immunology; Carcinoma; Carcinoma - genetics; Carcinoma - immunology; Carcinoma - mortality; Carcinoma - pathology; CD4 antigen; Cell surface; Cell-mediated immunity; Comparative analysis; Datasets as Topic; Female; Gene Expression Regulation, Neoplastic - immunology; Gene set enrichment analysis; Gene silencing; Genes; Genetic aspects; Genetic engineering; Genomics; Hepatocellular carcinoma; Humans; Immune response (cell-mediated); Immunological memory; Immunology; Immunotherapy; Infiltration; Kaplan-Meier Estimate; Liver cancer; Lymphocytes B; Lymphocytes T; Macrophages; Male; Mast cells; Medical prognosis; Melanoma; Memory cells; Metastases; Metastasis; Microenvironments; Middle Aged; Molecular modelling; Monocytes; Mutation; Neurodegenerative diseases; Polymerase chain reaction; Prognosis; Proteins; Risk Assessment - methods; RNA, Long Noncoding - metabolism; Sensitivity analysis; Survival analysis; T cells; Tumor cell lines; Tumor Microenvironment - genetics; Tumor Microenvironment - immunology; Tumors; Uterine cancer; Uterus; β-Site APP-cleaving enzyme 1
• ISSN: 2314-8861; 2314-7156
• DOI: 10.1155/2021/1589864

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.