Systematic Analyses of the Differentially Expressed Alternative Splicing Events in Gastric Cancer and Its Clinical Significance

Abstract

Accumulation of evidence has indicated a close relationship between alternative splicing (AS) and gastric cancer (GC), whereas systematic analyses of the differentially expressed AS events (DEAS) between GC and normal tissues are lacking. RNA-Seq data and the corresponding clinical information were downloaded from TCGA GC cohort. The percent spliced-in (PSI) value calculated in the GC tissues and normal tissues was employed to quantify the DEAS. Further, survival-associated DEAS and DEAS signatures were identified by univariate and multivariate cox regression analyses. To evaluate the association between DEAS and patients’ clinical features, Kaplan-Meier analysis, receiver operator characteristic (ROC) curve, Cox proportional regression and nomograms incorporating the DEAS signatures were performed. DEAS and their splicing networks were finally analyzed by bioinformatics methods. In addition, we use the method of random grouping to divide the samples into the training group and the test group. The final results of the two groups are consistent. After strict filtering, a total of 44,935 AS events were identified, among which 11,141 DEAS were preliminarily screened from 5032 genes. A total of 454 DEAS was associated with OS, and 872 DEAS were associated with DFS. The final prognostic signatures were constructed from the survival-associated DEAS with an area under the receiver operating characteristic (ROC) curve (AUC) greater than 0.6. Only ES in ABI1 was simultaneously associated with OS and DFS. Finally, we identified the splicing correlation network between the prognostic splicing factors (SF) and DEAS in GC. Our study provided a systematic portrait of survival-associated DEAS in GC and uncovered splicing networks that are valuable in deciphering the underlying mechanisms of AS in GC.

Identification of alternative splicing associated with clinical features: from pan-cancers to genitourinary tumors

“…Among these, most reports focus on the relationship between aberrant ASEs and prognosis and survival in cancer patients. After identification of the overall survival-associated ASEs, prognostic models were developed to predict the survival outcomes of patients with aberrant AS patterns in gastric cancer (32)(33)(34)(35), breast cancer (36), CHOL (37), glioblastoma (38), pancreatic cancer (39), LAML (40), UVM (41), HNSC (42), etc. Aberrant AS is also related to chemotherapy resistance.…”

Survival-Associated Differentially Expressed Alternative Splicing Signatures Reveal Neuron Signaling and Metabolism-Related Processes in Glioblastoma

“…AS is the basic mechanism of gene expression regulation in eukaryotes, which increases the complexity of gene expression, promotes higher transcription e ciency, and protein diversity [15]. It has been found that the dysregulation of DEAS in cancer-related genes is involved in many biological processes of tumors, and these abnormally regulated genes can be used as molecular markers for cancer prognosis and treatment [16,17]. However, a comprehensive analysis of DEAS signatures in GBM remains unknown.…”

Polyadenylate-binding protein cytoplasmic 1 mediates alternative splicing events of immune-related genes in gastric cancer cells

“…These events have been discovered in the context of physiological diseases and some biological processes. 10,11 Splice variants are responsible for diversifying gene expression regulation, which functionally result in the diversity of proteomes and contribute to cell proliferation, migration, or immune escape. [12][13][14] According to the previous description, some compounds (e.g.…”