EFNA2 mediates stiffness-regulated hypopharyngeal cancer progression.

IF 2.9 3区医学 Q1 OTORHINOLARYNGOLOGY

Clinical and Experimental Otorhinolaryngology Pub Date : 2025-03-17 DOI:10.21053/ceo.2024.00315

Songqun Hu, Yuanru Liu, Min Cheng, Min Xu, Huiting Liu, Ying Shan, Haosheng Ni, Tian Xia, Qicheng Zhang, Zhenxin Zhang, Bo You

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引用次数: 0

Abstract

Objective: Hypopharyngeal cancer (HPC) originates from the hypopharyngeal mucosa with poor prognosis. The stiffness of extracellular matrix (ECM) is closely associated with tumor progression and prognosis. This study aimed to investigate the impact of matrix stiffness and identify molecular markers that are relevant to the prognosis of HPC, with the goal of improving prognosis.

Methods: Immunohistochemical and cervical enhanced CT data were used to analyze the correlation between CT value, matrix stiffness, and prognosis, and to establish prognosis prediction model of HPC. Cell culture models with different matrix stiffness were constructed by polypropylene hydrogel. Western blotting, clone formation, EDU, and Transwell were used to investigate the effects of matrix stiffness on proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT). High-throughput sequencing was used to identify differential genes in HPC cells cultured in different matrix stiffness. Gene editing technique, in vivo subcutaneous tumorigenesis studies, and western blotting were conducted to investigate molecular mechanisms underlying the impact of high-stiffness matrix on HPC, and the influence of EFNA2 on proliferation, migration, and EMT.

Results: The arterial CT value was positively correlated with matrix stiffness. Matrix stiffness is associated with lymph node metastasis, therapeutic effect, and prognosis. Additionally, metastatic lymph nodes in HPC patients had higher CT values compared to those in patients with nasopharyngeal carcinoma (NPC). High-stiffness ECM could promote the proliferation, migration and EMT of HPC cells. Mechanistically, highstiffness ECM infuenced EFNA2 expression to promote proliferation, migration, EMT, and tumor growth in vivo.

Conclusion: EFNA2 and high matrix stiffness jointly promoted the malignant phenotype in HPC. EFNA2 may serve as potential therapeutic target for high matrix stiffnessinduced HPC progression.

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来源期刊

Clinical and Experimental Otorhinolaryngology 医学-耳鼻喉科学

CiteScore

4.90

自引率

6.70%

发文量

审稿时长

6-12 weeks

期刊介绍： Clinical and Experimental Otorhinolaryngology (Clin Exp Otorhinolaryngol, CEO) is an international peer-reviewed journal on recent developments in diagnosis and treatment of otorhinolaryngology-head and neck surgery and dedicated to the advancement of patient care in ear, nose, throat, head, and neck disorders. This journal publishes original articles relating to both clinical and basic researches, reviews, and clinical trials, encompassing the whole topics of otorhinolaryngology-head and neck surgery. CEO was first issued in 2008 and this journal is published in English four times (the last day of February, May, August, and November) per year by the Korean Society of Otorhinolaryngology-Head and Neck Surgery. The Journal aims at publishing evidence-based, scientifically written articles from different disciplines of otorhinolaryngology field. The readership contains clinical/basic research into current practice in otorhinolaryngology, audiology, speech pathology, head and neck oncology, plastic and reconstructive surgery. The readers are otolaryngologists, head and neck surgeons and oncologists, audiologists, and speech pathologists.