The Role of Alternative Splicing Factors hnRNP G and Fox-2 in the Progression and Prognosis of Esophageal Cancer

Author:

Zheng Yuanyuan12ORCID,Niu Xiaoyu3,Xue Wenhua1ORCID,Li Lifeng24,Geng Qishun12,Fan Zhirui5ORCID,Zhao Jie12ORCID

Affiliation:

1. Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China

2. Internet Medical and System Applications of National Engineering Laboratory, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China

3. Department of Anesthesiology, Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China

4. Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China

5. Integrated Traditional and Western Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China

Abstract

Aim. Alternative splicing (AS) has been widely demonstrated in the occurrence and progression of many cancers. Nevertheless, the involvement of cancer-associated splicing factors in the development of esophageal carcinoma (ESCA) remains to be explored. Method. RNA-Seq data and the corresponding clinical information of the ESCA cohort were downloaded from The Cancer Genome Atlas database. Bioinformatics methods were used to further analyzed the differently expressed AS (DEAS) events and their splicing network. Kaplan–Meier, Cox regression, and unsupervised cluster analyses were used to assess the association between AS events and clinical characteristics of ESCA patients. The splicing factors screened out were verified in vitro at the cellular level. Results. A total of 50,342 AS events were identified, of which 3,988 were DEAS events and 46 of these were associated with overall survival (OS) of ESCA patients, with a 5-year OS rate of 0.941. By constructing a network of AS events with survival-related splicing factors, the AS factors related to prognosis can be further identified. In vitro experiments and database analysis confirmed that the high expression of hnRNP G in ESCA is related to the high invasion ability of ESCA cells and the poor prognosis of ESCA patients. In contrast, the low expression of fox-2 in esophageal cancer is related to a better prognosis. Conclusion. ESCA-associated AS factors hnRNP G and Fox-2 are of great value in deciphering the underlying mechanisms of AS in ESCA and providing clues for therapeutic goals for further validation.

Funder

Medical Science and Technology Research Project in Henan Province

Publisher

Hindawi Limited

Subject

Biochemistry (medical),Clinical Biochemistry,Genetics,Molecular Biology,General Medicine

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