2. Academic Validation
  3. Alternative Splicing Factor HNRNPU as a Promising Biomarker for Gastric Cancer Risk and Prognosis with Tumor-Promoting Properties

Alternative Splicing Factor HNRNPU as a Promising Biomarker for Gastric Cancer Risk and Prognosis with Tumor-Promoting Properties

  • Am J Pathol. 2023 Nov 1:S0002-9440(23)00414-5. doi: 10.1016/j.ajpath.2023.10.007.
Ying-Ying Dong 1,  Meng-Ya Wang 2,  Jing-Jing Jing 1,  Yi-Jun Wu 1,  Hao Li 3,  Yuan Yuan 4,  Li-Ping Sun 5
Affiliations

Affiliations

  • 1 Tumor Etiology and Screening Department of Cancer Institute, and Key Laboratory of Cancer Etiology and Prevention in Liaoning Education Department, the First Hospital of China Medical University, Shenyang 110001, China; Key Laboratory of GI Cancer Etiology and Prevention in Liaoning Province, the First Hospital of China Medical University, Shenyang 110001, China.
  • 2 Tumor Etiology and Screening Department of Cancer Institute, and Key Laboratory of Cancer Etiology and Prevention in Liaoning Education Department, the First Hospital of China Medical University, Shenyang 110001, China; Department of Radiotherapy, Zhumadian Central Hospital, Zhumadian 463000, China.
  • 3 Department of Clinical Laboratory, the First Hospital of China Medical University, Shenyang 110001, China.
  • 4 Tumor Etiology and Screening Department of Cancer Institute, and Key Laboratory of Cancer Etiology and Prevention in Liaoning Education Department, the First Hospital of China Medical University, Shenyang 110001, China; Key Laboratory of GI Cancer Etiology and Prevention in Liaoning Province, the First Hospital of China Medical University, Shenyang 110001, China. Electronic address: yuanyuan@cmu.edu.cn.
  • 5 Tumor Etiology and Screening Department of Cancer Institute, and Key Laboratory of Cancer Etiology and Prevention in Liaoning Education Department, the First Hospital of China Medical University, Shenyang 110001, China; Key Laboratory of GI Cancer Etiology and Prevention in Liaoning Province, the First Hospital of China Medical University, Shenyang 110001, China. Electronic address: lpsun@cmu.edu.cn.
PMID: 37923250 DOI: 10.1016/j.ajpath.2023.10.007
Abstract

Gastric Cancer (GC) is a major global health concern with poor outcomes. HNRNPU is a multifunctional protein that participates in pre-mRNA packaging, alternative splicing regulation, and chromatin remodeling. Its potential role in GC remains unclear. In this study, the expression characteristics of HNRNPU were analyzed by the TCGA data, GEO data, then further identified by real-time quantitative PCR and immunohistochemistry using tissue specimens. From superficial gastritis, atrophic gastritis, hyperplasia to GC, the in situ expression of HNRNPU protein gradually increased, and the AUCs for diagnosis of GC and its precancerous lesions, GC were 0.911, 0.847, respectively. A nomogram integrating HNRNPU expression, lymph node metastasis and other prognostic indicators exhibited an AUC of 0.785 for predicting survival risk. Knockdown of HNRNPU significantly inhibited GC cell proliferation, migration, invasion and promoted Apoptosis in vitro. Additionally, RNA-seq analysis showed that HNRNPU could affect alternative splicing events in GC cells, with functional enrichment analysis revealing that HNRNPU may exert malignant biological function in GC progression through alternative splicing regulation. In summary, the increased expression of HNRNPU was significantly associated with the development of GC, with a good performance in diagnosing and predicting the prognostic risk of GC. Functionally, HNRNPU may play an oncogenic role in GC by regulating alternative splicing.

Keywords

HNRNPU; alternative splicing; gastric cancer; prognosis; risk.

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