Research Paper Volume 15, Issue 22 pp 13287—13311
Molecular characteristics and clinical implications of serine/arginine-rich splicing factors in human cancer
- 1 Department of Emergency Medicine, Taihe Hospital, Hubei University of Medicine, Shiyan, China
- 2 Department of Thoracic Surgery, Renmin Hospital of Wuhan University, Wuhan, China
Received: July 17, 2023 Accepted: October 17, 2023 Published: November 24, 2023
https://doi.org/10.18632/aging.205241How to Cite
Copyright: © 2023 Zhang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
As critical splicing regulators, serine/arginine-rich splicing factors (SRSFs) play pivotal roles in carcinogenesis. As dysregulation of SRSFs may confer potential cancer risks, targeting SRSFs could provide important insights into cancer therapy. However, a global and comprehensive pattern to elaborate the molecular characteristics, mechanisms, and clinical links of SRSFs in a wide variety of human cancer is still lacking. In this study, a systematic analysis was conducted to reveal the molecular characteristics and clinical implications of SRSFs covering more than 10000 tumour samples of 33 human cancer types. We found that SRSFs experienced prevalent genomic alterations and expression perturbations in multiple cancer types. The DNA methylation, m6A modification, and miRNA regulation of SRSFs were all cancer context-dependent. Importantly, we found that SRSFs were strongly associated with cancer immunity, and were capable of predicting response to immunotherapy. And SRSFs had colossal potential for predicting survival in multiple cancer types, including those that have received immunotherapy. Moreover, we also found that SRSFs could indicate the drug sensitivity of targeted therapy and chemotherapy. Our research highlights the significance of SRSFs in cancer occurrence and development, and provides sufficient resources for understanding the biological characteristics of SRSFs, offering a new and unique perspective for developing cancer therapeutic strategies.
Abbreviations
SRSF: Serine/arginine-rich splicing factor; TGGA: The Cancer Genome Atlas; ACC: Adrenocortical Carcinoma; BLCA: Bladder Urothelial Carcinoma; BRCA: Breast Cancer; CESC: Cervical Aquamous Cell Carcinoma and Endocervical Adenocarcinoma; CHOL: Cholangiocarcinoma; COAD: Colon Adenocarcinoma; DLBC: Lymphageal Neoplasm Diffuse Large B-Cell Lymphoma; ESCA: Esophageal Carcinoma; GBM: Glioblastoma Multiforme; HNSC: Head And Neck Squamous Carcinoma; READ: Rectum Adenocarcinoma; KICH: Kidney Chromophobe; KIRC: Kidney Renal Clear Cell Carcinoma; KIRP: Kidney Renal Papillary Cell Carcinoma; LAML: Acute Myeloid Leukemia; LGG: Brain Lower Grade Glioma; LIHC: Liver Hepatocellular Carcinoma; LUAD: Lung Adenocarcinoma; LUSC: Lung Squamous cell carcinoma; MESO: Mesothelioma; OV: Ovarian serous cystadenocarcinoma; PADD: Pancereatic Adenocarcinoma; PCPG: Pheochromocytoma and Paraganglima; PRAD: Prostate Adenocarcinoma; SARC: Sarcoma; SKCM: Skin Cutaneous Melanoma; STAD: Stomach Adenocarcinoma; TGCT: Testicular Germ Cell Tumors; THCA: Thyroid Carcinoma; THYM: Thymoma; UCEC: Uterine Corpus Endometrial Carcinoma; UCS: Uterine Carcinosarcoma; UVM: Uveal Melanoma; GSEA: Gene-Set Enrichment Analysis; CNV: copy number variation; GSVA: Gene set variation analysis; SCNA: Somatic copy number alterations; LOH: Loss of heterozygosity; HRD: Homologous recombination deficiency.