Identification of key hub genes and potential therapeutic drugs for nasopharyngeal carcinoma: Insights into molecular mechanisms and treatment strategies

Objective: Nasopharyngeal Carcinoma (NPC) is a highly malignant cancer with a high incidence in East and Southeast Asia, including southern China. Despite advances in treatment, the prognosis for advanced NPC remains poor due to high recurrence and metastasis rates. The molecular mechanisms driving...

Full description

Saved in:
Bibliographic Details
Main Authors: Haiyan Quan, Hongguo Yin, Zhen Wang, Yuan Lv, Qiong Sun, Ting Yin
Format: Article
Language:English
Published: Elsevier 2025-07-01
Series:Brazilian Journal of Otorhinolaryngology
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S1808869425000618
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1849714579832045568
author Haiyan Quan
Hongguo Yin
Zhen Wang
Yuan Lv
Qiong Sun
Ting Yin
author_facet Haiyan Quan
Hongguo Yin
Zhen Wang
Yuan Lv
Qiong Sun
Ting Yin
author_sort Haiyan Quan
collection DOAJ
description Objective: Nasopharyngeal Carcinoma (NPC) is a highly malignant cancer with a high incidence in East and Southeast Asia, including southern China. Despite advances in treatment, the prognosis for advanced NPC remains poor due to high recurrence and metastasis rates. The molecular mechanisms driving NPC progression are not fully understood, and identifying key genes and potential therapeutic agents is critical. This study aims to uncover critical genes and screen therapeutic drugs, providing insights into NPC pathogenesis and novel treatment strategies. Methods: Three GEO datasets (GSE12452, GSE53819, and GSE61218) were analyzed to identify overlapping Differentially Expressed Genes (DEGs) in NPC. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) were used to explore the biological roles of DEGs. Protein-Protein Interaction (PPI) and mRNA-miRNA-lncRNA interaction networks were constructed to identify key hub genes. Potential therapeutic drugs were predicted via a Drug-Gene Interaction network. The overexpression of hub genes was validated in NPC cells using CCK-8 assays, and the anti-proliferative effects of three drugs ‒ valproic acid, cyclosporine, and calcitriol ‒ were tested. Results: Eight hub genes (ASPM, BIRC5, BUB1B, CDK1, KIF23, PBK, TOP2A, and TTK) were identified, with ASPM reported for the first time in the context of NPC. Overexpression of these genes significantly promoted NPC cell proliferation. Among the tested drugs, calcitriol exhibited the most potent anti-proliferative effect, with IC50 values of 0.90 μM, 0.47 μM, and 0.31 μM at 24-, 48-, and 72-hs, respectively. Conclusion: This study identified eight key genes as potential biomarkers for NPC and validated calcitriol as a promising therapeutic agent, providing a foundation for further research into NPC treatment. Level of evidence: Level 2 (Individual cross-sectional studies or systematic review of surveys that allow matching to local circumstances).
format Article
id doaj-art-9cdd05ba3fea4c3ba92d47d0910e6cb3
institution DOAJ
issn 1808-8694
language English
publishDate 2025-07-01
publisher Elsevier
record_format Article
series Brazilian Journal of Otorhinolaryngology
spelling doaj-art-9cdd05ba3fea4c3ba92d47d0910e6cb32025-08-20T03:13:39ZengElsevierBrazilian Journal of Otorhinolaryngology1808-86942025-07-0191410161810.1016/j.bjorl.2025.101618Identification of key hub genes and potential therapeutic drugs for nasopharyngeal carcinoma: Insights into molecular mechanisms and treatment strategiesHaiyan Quan0Hongguo Yin1Zhen Wang2Yuan Lv3Qiong Sun4Ting Yin5Hunan Polytechnic of Environment and Biology, Hengyang, Hunan, ChinaHunan Polytechnic of Environment and Biology, Hengyang, Hunan, ChinaHunan Polytechnic of Environment and Biology, Hengyang, Hunan, ChinaHunan Polytechnic of Environment and Biology, Hengyang, Hunan, ChinaHunan Polytechnic of Environment and Biology, Hengyang, Hunan, ChinaDepartment of Ophthalmology, The Second Affiliated Hospital, University of South China, Hengyang, Hunan, China; Corresponding authorObjective: Nasopharyngeal Carcinoma (NPC) is a highly malignant cancer with a high incidence in East and Southeast Asia, including southern China. Despite advances in treatment, the prognosis for advanced NPC remains poor due to high recurrence and metastasis rates. The molecular mechanisms driving NPC progression are not fully understood, and identifying key genes and potential therapeutic agents is critical. This study aims to uncover critical genes and screen therapeutic drugs, providing insights into NPC pathogenesis and novel treatment strategies. Methods: Three GEO datasets (GSE12452, GSE53819, and GSE61218) were analyzed to identify overlapping Differentially Expressed Genes (DEGs) in NPC. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) were used to explore the biological roles of DEGs. Protein-Protein Interaction (PPI) and mRNA-miRNA-lncRNA interaction networks were constructed to identify key hub genes. Potential therapeutic drugs were predicted via a Drug-Gene Interaction network. The overexpression of hub genes was validated in NPC cells using CCK-8 assays, and the anti-proliferative effects of three drugs ‒ valproic acid, cyclosporine, and calcitriol ‒ were tested. Results: Eight hub genes (ASPM, BIRC5, BUB1B, CDK1, KIF23, PBK, TOP2A, and TTK) were identified, with ASPM reported for the first time in the context of NPC. Overexpression of these genes significantly promoted NPC cell proliferation. Among the tested drugs, calcitriol exhibited the most potent anti-proliferative effect, with IC50 values of 0.90 μM, 0.47 μM, and 0.31 μM at 24-, 48-, and 72-hs, respectively. Conclusion: This study identified eight key genes as potential biomarkers for NPC and validated calcitriol as a promising therapeutic agent, providing a foundation for further research into NPC treatment. Level of evidence: Level 2 (Individual cross-sectional studies or systematic review of surveys that allow matching to local circumstances).http://www.sciencedirect.com/science/article/pii/S1808869425000618Nasopharyngeal carcinomaKey genesDrug screeningCalcitriol
spellingShingle Haiyan Quan
Hongguo Yin
Zhen Wang
Yuan Lv
Qiong Sun
Ting Yin
Identification of key hub genes and potential therapeutic drugs for nasopharyngeal carcinoma: Insights into molecular mechanisms and treatment strategies
Brazilian Journal of Otorhinolaryngology
Nasopharyngeal carcinoma
Key genes
Drug screening
Calcitriol
title Identification of key hub genes and potential therapeutic drugs for nasopharyngeal carcinoma: Insights into molecular mechanisms and treatment strategies
title_full Identification of key hub genes and potential therapeutic drugs for nasopharyngeal carcinoma: Insights into molecular mechanisms and treatment strategies
title_fullStr Identification of key hub genes and potential therapeutic drugs for nasopharyngeal carcinoma: Insights into molecular mechanisms and treatment strategies
title_full_unstemmed Identification of key hub genes and potential therapeutic drugs for nasopharyngeal carcinoma: Insights into molecular mechanisms and treatment strategies
title_short Identification of key hub genes and potential therapeutic drugs for nasopharyngeal carcinoma: Insights into molecular mechanisms and treatment strategies
title_sort identification of key hub genes and potential therapeutic drugs for nasopharyngeal carcinoma insights into molecular mechanisms and treatment strategies
topic Nasopharyngeal carcinoma
Key genes
Drug screening
Calcitriol
url http://www.sciencedirect.com/science/article/pii/S1808869425000618
work_keys_str_mv AT haiyanquan identificationofkeyhubgenesandpotentialtherapeuticdrugsfornasopharyngealcarcinomainsightsintomolecularmechanismsandtreatmentstrategies
AT hongguoyin identificationofkeyhubgenesandpotentialtherapeuticdrugsfornasopharyngealcarcinomainsightsintomolecularmechanismsandtreatmentstrategies
AT zhenwang identificationofkeyhubgenesandpotentialtherapeuticdrugsfornasopharyngealcarcinomainsightsintomolecularmechanismsandtreatmentstrategies
AT yuanlv identificationofkeyhubgenesandpotentialtherapeuticdrugsfornasopharyngealcarcinomainsightsintomolecularmechanismsandtreatmentstrategies
AT qiongsun identificationofkeyhubgenesandpotentialtherapeuticdrugsfornasopharyngealcarcinomainsightsintomolecularmechanismsandtreatmentstrategies
AT tingyin identificationofkeyhubgenesandpotentialtherapeuticdrugsfornasopharyngealcarcinomainsightsintomolecularmechanismsandtreatmentstrategies