Prognostic Alternative Splicing Signatures in Esophageal Carcinoma

Abstract

Alternative splicing (AS) is a method of increasing the number of proteins that the genome is capable of coding for, by altering the pre-mRNA during its maturation. This process provides the ability of a broad range of proteins to arise from a single gene. AS events are known to occur in up to 94% of human genes. Cumulative data have shown that aberrant AS functionality is a major factor in human diseases. This review focuses on the contribution made by aberrant AS functionality in the development and progression of esophageal cancer. The changes in the pattern of expression of alternately spliced isoforms in esophageal cancer can be used as diagnostic or prognostic biomarkers. Additionally, these can be used as targets for the development of new treatments for esophageal cancer.

Exploiting the Molecular Basis of Oesophageal Cancer for Targeted Therapies and Biomarkers for Drug Response: Guiding Clinical Decision-Making

“…Figure 5 illustrates how alternately spliced isoforms could contribute to both cancer development and progression. Some of these different isoforms can be targeted as potential biomarkers for early cancer detection and diagnosis and as targets for novel therapeutics [ 95 ]. Examples of the targetable splice variants are listed in Table 4 .…”

“…This study identified 2326 AS events in 1738 genes that were differentially spliced in OSCC tissue compared to healthy oesophageal tissue. Of these alternately spliced genes, 1360 genes were predicted to be significantly associated with overall oesophageal cancer patient survival [ 95 ].…”

“…Splicing can also lead to the production of inactive versions of tumor suppressor proteins or even the activation of oncogenes and cancer pathways [ 45 ]. Some of these different isoforms can be targeted as potential biomarkers for early cancer detection and diagnosis and as targets for novel therapeutics [ 95 ]. The changes that can occur in alternative splicing that contribute to the development and progression of OSCC can also be targeted.…”

Serine-arginine splicing factor 2 promotes oesophageal cancer progression by regulating alternative splicing of interferon regulatory factor 3

“…In addition, studies have shown that most of the oncogenic splicing events in ESCC seem to be associated with increased expression of subtypes associated with increased proliferation, altered cell junctions, and increased cell migration [ 17 ]. These splicing events are characteristics of the transition from normal oesophageal tissue to oesophageal cancer and subsequent tumour progression and growth, resulting in many of these splicing variants being proposed as viable biomarkers for the diagnosis and prognosis of oesophageal cancer [ 18 ]. Although previous studies have shown that the progression of oesophageal cancer is closely related to AS, there are few studies on the specific mechanism of AS.…”

Transcriptome-Wide Analyses Identify Dominant as the Predominantly Non-Conservative Alternative Splicing Inheritance Patterns in F1 Chickens

“…Alternative splicing (AS) generates multiple isoforms from a single gene using different combinations of exons. AS is a widespread and complex component of gene regulation in humans and domestic animals, and increasing evidence suggests that aberrant AS functionality can be the cause or consequence of many diseases, and may also associating with economically important traits in domestic animals ( Pan et al, 2008 ; Merkin et al, 2012 ; Gao et al, 2018 ; Dlamini et al, 2021 ). Therefore, splice-altering therapies using animal models have been extensively studied for many diseases such as neurodegeneration and muscular dystrophies, and AS events have also emerged as new biomarkers in some circumstances ( Montes et al, 2019 ; Zhao, 2019 ).…”