Correlations Between the Characteristics of Alternative Splicing Events, Prognosis, and the Immune Microenvironment in Breast Cancer

Abstract

ObjectiveAlternative splicing (AS) is the mechanism by which a few genes encode numerous proteins, and it redefines the concept of gene expression regulation. Recent studies showed that dysregulation of AS was an important cause of tumorigenesis and microenvironment formation. Therefore, we performed a systematic analysis to examine the role of AS in breast cancer (Breast Cancer, BrCa) progression.MethodsThe present study included 993 BrCa patients from The Cancer Genome Atlas (TCGA) database in the genome-wide analysis of AS events. We used differential and prognostic analyses and found differentially expressed alternative splicing (DEAS) events and independent prognostic factors related to patients’ overall survival (OS) and disease-free survival (DFS). We divided the patients into two groups based on these AS events and analyzed their clinical features, molecular subtyping and immune characteristics. We also constructed a splicing factor (SF) regulation network for key AS events and verified the existence of AS events in tissue samples using real-time quantitative PCR.ResultsA total of 678 AS events were identified as differentially expressed, of which 13 and 10 AS events were independent prognostic factors of patients’ OS and DFS, respectively. Unsupervised clustering analysis based on these prognostic factors indicated that the Cluster 1 group had a better prognosis and more immune cell infiltration. SFs were significantly related to the expression of AS events, and AA-RPS21 was significantly upregulated in tumors.ConclusionAlternative splicing expands the mechanism of breast cancer progression from a new perspective. Notably, alternative splicing may affect the patient’s prognosis by affecting the infiltration of immune cells. Our research provides important guidance for subsequent studies of AS in breast cancer.

SPRI: Spatial Pattern Recognition using Information based method for spatial gene expression data

“…9) indicates that three of them have been found associated with breast cancer, including, RPS21, PPP1CA and TXNIP. RPS21 ’s role in breast cancer is not clear now, but one transcript of RPS, AA-RPS21 , is differentially expressed in cancerous tissues, indicating its potential driver role in breast cancer [34]. PPP1CA together with PRKACG and PRKAR1B were found to be the most strongly associated with breast cancer–specific survival [35].…”

A comprehensive characterization of alternative splicing events related to prognosis and the tumor microenvironment in lung adenocarcinoma

“…The potential to use cancer-specific AS events as biomarkers for prognosis and treatment targets is gaining recognition (36,37). Recent studies have focused on exploring the prognostic value of AS events in malignancies such as colorectal cancer (38), breast cancer (39), hepatocellular carcinoma (40), and kidney cancer (41). LUAD is an aggressive tumor with increasing incidence and poor outcomes (42), and thus, the identification of biomarkers for diagnosis and therapy is urgently required.…”

Immunomodulatory Gene-Splicing Dysregulation in Tumorigenesis: Unmasking the Complexity

“…The dysregulation of an immune response is associated with oncogenesis [ 14 , 15 ]. Studies have indicated the implication of alternative splicing in immune dysregulation [ 16 ] and also the presence of abnormal isoforms and their aberrant expression levels as cancer hallmarks [ 17 ]. This review unmasks the complexity of immunomodulatory genes splicing dysregulation in carcinogenesis.…”