Systematic profiling of alternative splicing signature reveals prognostic predictor for cervical cancer

J Transl Med. 2019 Nov 19;17(1):379. doi: 10.1186/s12967-019-02140-x.

Abstract

Aim: Cervical cancer is a common malignant carcinoma of the gynecological tract with high morbidity and mortality. Therefore, it is crucial to elucidate the pathogenesis, prevention, diagnosis and prognosis of cervical cancer by searching for the involved key genes.

Method: In this study, the alternative splicing (AS) events of 253 patients with cervical cancer were analyzed, and 41,766 AS events were detected in 9961 genes. Univariate analysis was performed to screen prognostic AS events. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis was used to identify the pathways in which these AS events were involved.

Results: We found that exon skip (ES) is the main AS event in patients with cervical cancer. There was pronounced consistency between the genes involved in overall survival and those involved in recurrence. At the same time, we found that a gene may exhibit several different types of AS events, and these different AS events may be related to prognosis. Four characteristic genes, HSPA14, SDHAF2, CAMKK2 and TM9SF1, that can be used as prognostic markers for cervical cancer were selected.

Conclusion: The importance of AS events in the development of cervical cancer and prediction of prognosis was revealed by a large amount of data at the whole genome level, which may provide a potential target for cervical cancer treatment. We also provide a new method for exploring the pathogenesis of cervical cancer to determine clinical treatment and prognosis more accurately.

Keywords: Alternative splicing; Cervical cancer; Prognosis; TCGA; Whole genome level.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alternative Splicing / genetics*
  • Exons / genetics
  • Factor Analysis, Statistical
  • Female
  • Gene Expression Profiling*
  • Gene Expression Regulation, Neoplastic*
  • Gene Regulatory Networks
  • Genes, Neoplasm
  • Humans
  • Kaplan-Meier Estimate
  • Multivariate Analysis
  • Neoplasm Recurrence, Local / genetics
  • Prognosis
  • Transcription, Genetic
  • Uterine Cervical Neoplasms / classification
  • Uterine Cervical Neoplasms / genetics*