Hongliang Du, Zhenze Wang, Mengyi Qi, Yunqing Pang, Qingling Lin, Dengqi He, Jing Wang
{"title":"利用全转录组测序和生物信息学分析鉴定与口腔鳞状细胞癌相关的新生物标志物。","authors":"Hongliang Du, Zhenze Wang, Mengyi Qi, Yunqing Pang, Qingling Lin, Dengqi He, Jing Wang","doi":"10.1186/s12935-025-03913-9","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Oral squamous cell carcinoma (OSCC) is among the most common malignant tumors in the oral and maxillofacial regions, characterized by high drug resistance and poor treatment outcomes. This underscores the urgent need to identify novel biomarkers for OSCC.</p><p><strong>Methods: </strong>Differentially expressed messenger RNAs (mRNAs), microRNAs (miRNAs), and long non-coding RNAs (lncRNAs) (DE-mRNAs, DE-miRNAs, and DE-lncRNAs) between primary and control groups, as well as metastatic and primary groups, were identified using whole transcriptome sequencing data. Candidate OSCC genes were derived from DE-mRNAs. Potential biomarkers were then identified using five algorithms from CytoHubba. Biomarkers were validated via univariate Cox regression and Kaplan-Meier (K-M) survival analysis. Additional analyses included subcellular localization, mutation analysis, and Gene Set Enrichment Analysis (GSEA). Key drugs for OSCC treatment were also identified. Quantitative real time polymerase chain reaction (qRT-PCR) and immunohistochemistry were employed to verify the expression levels of key biomarkers.</p><p><strong>Results: </strong>A total of 304 candidate genes were identified, with 29 potential biomarkers selected by five algorithms. ANPEP, APOB, GLP1R, and SI exhibited significant survival differences in the K-M curves, establishing them as OSCC biomarkers. These biomarkers were predominantly localized in the cytoplasm, with SI and APOB showing the highest mutation susceptibility. Enrichment analysis revealed that the 'interferon-gamma response'biological function was co-enriched by ANPEP, APOB, and SI. Furthermore, BIBW2992 (afatinib) and PF.02341066 (crizotinib) were most strongly correlated with the biomarkers, suggesting their potential as key drugs for OSCC treatment. Additionally, the findings were validated by qRT-PCR and immunohistochemical analyses, and the results were consistent with the RNA-seq data.</p><p><strong>Conclusion: </strong>ANPEP, APOB, GLP1R, and SI were identified as potential OSCC biomarkers, offering valuable insights for further research and therapeutic development.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"277"},"PeriodicalIF":6.0000,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12285194/pdf/","citationCount":"0","resultStr":"{\"title\":\"Identification of novel biomarkers involved in oral squamous cell carcinoma by whole transcriptome sequencing and bioinformatics analysis.\",\"authors\":\"Hongliang Du, Zhenze Wang, Mengyi Qi, Yunqing Pang, Qingling Lin, Dengqi He, Jing Wang\",\"doi\":\"10.1186/s12935-025-03913-9\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Oral squamous cell carcinoma (OSCC) is among the most common malignant tumors in the oral and maxillofacial regions, characterized by high drug resistance and poor treatment outcomes. This underscores the urgent need to identify novel biomarkers for OSCC.</p><p><strong>Methods: </strong>Differentially expressed messenger RNAs (mRNAs), microRNAs (miRNAs), and long non-coding RNAs (lncRNAs) (DE-mRNAs, DE-miRNAs, and DE-lncRNAs) between primary and control groups, as well as metastatic and primary groups, were identified using whole transcriptome sequencing data. Candidate OSCC genes were derived from DE-mRNAs. Potential biomarkers were then identified using five algorithms from CytoHubba. Biomarkers were validated via univariate Cox regression and Kaplan-Meier (K-M) survival analysis. Additional analyses included subcellular localization, mutation analysis, and Gene Set Enrichment Analysis (GSEA). Key drugs for OSCC treatment were also identified. Quantitative real time polymerase chain reaction (qRT-PCR) and immunohistochemistry were employed to verify the expression levels of key biomarkers.</p><p><strong>Results: </strong>A total of 304 candidate genes were identified, with 29 potential biomarkers selected by five algorithms. ANPEP, APOB, GLP1R, and SI exhibited significant survival differences in the K-M curves, establishing them as OSCC biomarkers. These biomarkers were predominantly localized in the cytoplasm, with SI and APOB showing the highest mutation susceptibility. Enrichment analysis revealed that the 'interferon-gamma response'biological function was co-enriched by ANPEP, APOB, and SI. Furthermore, BIBW2992 (afatinib) and PF.02341066 (crizotinib) were most strongly correlated with the biomarkers, suggesting their potential as key drugs for OSCC treatment. Additionally, the findings were validated by qRT-PCR and immunohistochemical analyses, and the results were consistent with the RNA-seq data.</p><p><strong>Conclusion: </strong>ANPEP, APOB, GLP1R, and SI were identified as potential OSCC biomarkers, offering valuable insights for further research and therapeutic development.</p>\",\"PeriodicalId\":9385,\"journal\":{\"name\":\"Cancer Cell International\",\"volume\":\"25 1\",\"pages\":\"277\"},\"PeriodicalIF\":6.0000,\"publicationDate\":\"2025-07-22\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12285194/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Cancer Cell International\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1186/s12935-025-03913-9\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cancer Cell International","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s12935-025-03913-9","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ONCOLOGY","Score":null,"Total":0}
Identification of novel biomarkers involved in oral squamous cell carcinoma by whole transcriptome sequencing and bioinformatics analysis.
Background: Oral squamous cell carcinoma (OSCC) is among the most common malignant tumors in the oral and maxillofacial regions, characterized by high drug resistance and poor treatment outcomes. This underscores the urgent need to identify novel biomarkers for OSCC.
Methods: Differentially expressed messenger RNAs (mRNAs), microRNAs (miRNAs), and long non-coding RNAs (lncRNAs) (DE-mRNAs, DE-miRNAs, and DE-lncRNAs) between primary and control groups, as well as metastatic and primary groups, were identified using whole transcriptome sequencing data. Candidate OSCC genes were derived from DE-mRNAs. Potential biomarkers were then identified using five algorithms from CytoHubba. Biomarkers were validated via univariate Cox regression and Kaplan-Meier (K-M) survival analysis. Additional analyses included subcellular localization, mutation analysis, and Gene Set Enrichment Analysis (GSEA). Key drugs for OSCC treatment were also identified. Quantitative real time polymerase chain reaction (qRT-PCR) and immunohistochemistry were employed to verify the expression levels of key biomarkers.
Results: A total of 304 candidate genes were identified, with 29 potential biomarkers selected by five algorithms. ANPEP, APOB, GLP1R, and SI exhibited significant survival differences in the K-M curves, establishing them as OSCC biomarkers. These biomarkers were predominantly localized in the cytoplasm, with SI and APOB showing the highest mutation susceptibility. Enrichment analysis revealed that the 'interferon-gamma response'biological function was co-enriched by ANPEP, APOB, and SI. Furthermore, BIBW2992 (afatinib) and PF.02341066 (crizotinib) were most strongly correlated with the biomarkers, suggesting their potential as key drugs for OSCC treatment. Additionally, the findings were validated by qRT-PCR and immunohistochemical analyses, and the results were consistent with the RNA-seq data.
Conclusion: ANPEP, APOB, GLP1R, and SI were identified as potential OSCC biomarkers, offering valuable insights for further research and therapeutic development.
期刊介绍：
Cancer Cell International publishes articles on all aspects of cancer cell biology, originating largely from, but not limited to, work using cell culture techniques.
The journal focuses on novel cancer studies reporting data from biological experiments performed on cells grown in vitro, in two- or three-dimensional systems, and/or in vivo (animal experiments). These types of experiments have provided crucial data in many fields, from cell proliferation and transformation, to epithelial-mesenchymal interaction, to apoptosis, and host immune response to tumors.
Cancer Cell International also considers articles that focus on novel technologies or novel pathways in molecular analysis and on epidemiological studies that may affect patient care, as well as articles reporting translational cancer research studies where in vitro discoveries are bridged to the clinic. As such, the journal is interested in laboratory and animal studies reporting on novel biomarkers of tumor progression and response to therapy and on their applicability to human cancers.
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