Pathogenic loss-of-function mutations in LRP1B are associated with poor survival in head and neck cancer patients.

Autor: Arumugam P; Molecular Biology Laboratory, Saveetha Dental College and Hospital, Saveetha Institute of Medical and Technical Sciences (SIMATS), Saveetha University, Chennai, India. Electronic address: paramasivama.sdc@saveetha.com., M SM; Department of Oral and Maxillofacial Surgery, Saveetha Dental College and Hospital, Saveetha Institute of Medical and Technical Sciences (SIMATS), Saveetha University, Chennai, India., Jayaseelan VP; Clinical Genetics Laboratory, Saveetha Dental College and Hospital, Saveetha Institute of Medical and Technical Sciences (SIMATS), Saveetha University, Chennai, India.
Jazyk: angličtina
Zdroj: Journal of stomatology, oral and maxillofacial surgery [J Stomatol Oral Maxillofac Surg] 2024 Oct; Vol. 125 (5S2), pp. 101971. Date of Electronic Publication: 2024 Jul 18.
DOI: 10.1016/j.jormas.2024.101971
Abstrakt: Objective: Head and neck squamous cell carcinoma (HNSCC) present a significant challenge in the medical field due to treatment resistance, which often hinders successful outcomes. The dysregulation of the LRP1B gene is linked to various cancers, but its specific role in HNSCC is poorly understood.
Methods: This study investigated the link between pathogenic loss-of-function mutations in the LRP1B gene and survival outcomes in HNSCC patients. The Cancer Genome Atlas HNSCC cohort, comprised of 520 tumor and 44 normal tissues, was analyzed using cBioportal, and UALCAN tools. Expression patterns, survival outcomes, and clinical correlations of LRP1B were evaluated. In-depth analyses involved validation of mRNA expression using RT-qPCR and functional exploration using various in-silico tools.
Results: Analysis of data from The Cancer Genome Atlas (TCGA) and cBioPortal revealed a high frequency (25 %) of LRP1B mutations in HNSCC patients. Notably, splice mutation, truncating mutation, and deep deletion, considered potential drivers, are commonly associated with LRP1B mutations. Patients with LRP1B mutations also exhibit poorer overall survival rates compared to those without these mutations. Furthermore, LRP1B mRNA expression is significantly reduced in HNSCC tissues compared to normal tissues and is correlated with advanced tumor stage, higher tumor grade, and nodal metastasis.
Conclusion: These findings indicate that LRP1B may function as both a prognostic biomarker and a therapeutic target in HNSCC patients.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier Masson SAS. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: