Systematic profiling of alternative splicing in Helicobacter pylori-negative gastric cancer and their clinical significance

Abstract

Background: Alternative splicing (AS) may cause structural and functional variations in the protein to promote the proliferation of tumor cells. However, there is no comprehensive analysis of the clinical significance of AS in Helicobacter pylori-negative gastric cancer (HP − GC). Methods: The clinical, gene expression profile data and AS events of 138 HP − GC patients were obtained from the database named the cancer genome atlas. Differently expressed AS (DEAS) events were determined by a comparison of the PSI values between HP − GC samples and adjacent normal samples. Unsupervised clustering analysis, proportional regression and Kaplan-Meier analysis were used to explore the association between clinical data and immune features and to establish two nomograms about the prognosis of HP − GC. Finally, splicing networks were constructed using Cytoscape. Results: A total of 48141 AS events and 1041 DEAS events were found in HP − GC. Various functions and pathways of DEAS events parent genes were enriched, such as cell-substrate junction, cell leading edge, focal adhension, and AMPK signaling. Seven overall survival (OS)-related and seven disease-free survival (DFS)-related AS events were used to construct the prognostic signatures. Based on the independent prognostic factors, two nomograms were established and showed excellent performance. Then, splicing regulatory networks among the correlations suggested that splicing factors were significantly associated with prognostic DEASs. Finally, the unsupervised clustering analysis revealed that DEAS-based clusters were associated with clinical characteristics, tumor microenvironment, tumor mutation burden, and immune features. Conclusion: Seven OS-related and seven DFS-related AS events have been found to be correlated with the prognosis of HP − GC and can be used as prognostic factors to establish an effective nomogram.

hnRNPA2B1 regulates the alternative splicing of BIRC5 to promote gastric cancer progression

“…Efficient pre-mRNA splicing required both cis-elements and trans-acting regulators, and their dysregulations induce aberrantly spliced molecules, resulting in aberrant expression profiles. Several studies have demonstrated that splicing factors are frequently mutated or dysregulated in GC and pre-mRNA splicing is frequently deregulated in the disease, which may also correlate with prognostic value [ 27 , 28 ]. In addition, we and others have identified the molecular pathways that regulates stem cell marker CD44 variant isoform expression in GC [ 29 , 30 ].…”

Prognostic value of immune-related genes and comparative analysis of immune cell infiltration in lung adenocarcinoma: sex differences

“…As the two main components, TIICs and stromal cells were regarded as valuable factors affecting the effect of tumor immunotherapy [ 13 – 17 ]. It was reported that immune cells, such as T and B cells, macrophages, dendritic cells, monocytes, etc., interacted with tumor cells, were correlated to tumor cell proliferation, metastasis and prognosis [ 18 – 20 ]. Regulated by Tregs and M2 macrophages, tumor-infiltrating lymphocytes (TILs) were involved in the occurrence and progression of various cancers [ 21 – 25 ].…”

Identification of Prognostic Alternative Splicing Signature in Gastric Cancer

“…Currently, Chuan Liu et al 20 and Victoria E S Armero et al 21 had determined the prediction model of AS events in Helicobacter pylori-negative cohort and Epstein-Barr virus cohort of GC, respectively. However, the present study depicted the landscape of AS pro les within the entire GC cohort and respectively constructed the risk prediction model strati ed by 7 types of AS.…”