{"title":"TOP2A作为食管小细胞癌的预后生物标志物：一项综合生物信息学和免疫组织化学研究","authors":"Xiaolei Yin, Xiaopeng Li, Lili Mi, Jiaojiao Hou, Fei Yin","doi":"10.3389/fmolb.2025.1640881","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Small cell carcinoma of the esophagus (SCCE) is an infrequent but highly aggressive cancer with a poor prognosis. Given its low incidence, there is a lack of validated biomarkers to guide risk stratification and inform treatment decisions.</p><p><strong>Methods: </strong>We extracted Differentially expressed genes (DEGs) from the GSE111044 dataset using standard bioinformatics workflows. A network of interacting proteins was assembled to determine hub genes, and TOP2A and CDK1 were selected for immunohistochemical (IHC) validation in 76 SCCE tumor samples. IHC staining scores were analyzed for associations with clinicopathological features. Survival analysis was conducted using Kaplan-Meier estimations and Cox regression modeling to pinpoint independent prognostic factors. To further assess the clinical utility, TOP2A expression was combined with VALSG staging for risk stratification.</p><p><strong>Results: </strong>A comparison between SCCE and adjacent normal tissues revealed 1,202 DEGs. PPI network analysis highlighted two hub genes, TOP2A and CDK1, which IHC validated in 76 SCCE samples. High TOP2A expression was significantly associated with advanced TNM stage (p = 0.020) and deeper tumor invasion (p = 0.004). Multivariate Cox analysis identified high TOP2A expression (HR = 1.92, 95% CI: 1.30-2.82, p = 0.001) and VALSG stage (HR = 2.20, 95% CI: 1.07-4.50, p = 0.031) as independent predictors of prognosis. Time-dependent ROC analysis indicated that the AUCs for the VALSG stage alone were 0.626, 0.638, and 0.602 at 1-, 2-, and 3-year time intervals, respectively. TOP2A alone yielded slightly higher AUCs of 0.719, 0.632, and 0.676. Notably, the combination of TOP2A and VALSG provided the greatest predictive accuracy, achieving AUCs recorded at 0.721, 0.734, and 0.773 at the respective time points.</p><p><strong>Conclusion: </strong>This study suggests that TOP2A is a novel, independent prognostic biomarker in SCCE. When integrated with the VALSG staging system, TOP2A expression enhances risk stratification and may serve as a useful adjunct in clinical prognostication. These findings support its clinical utility while emphasizing the necessity for future studies to include prospective validation.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"12 ","pages":"1640881"},"PeriodicalIF":3.9000,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12321555/pdf/","citationCount":"0","resultStr":"{\"title\":\"TOP2A as a prognostic biomarker in small cell carcinoma of the esophagus: an integrated bioinformatics and immunohistochemical study.\",\"authors\":\"Xiaolei Yin, Xiaopeng Li, Lili Mi, Jiaojiao Hou, Fei Yin\",\"doi\":\"10.3389/fmolb.2025.1640881\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Small cell carcinoma of the esophagus (SCCE) is an infrequent but highly aggressive cancer with a poor prognosis. Given its low incidence, there is a lack of validated biomarkers to guide risk stratification and inform treatment decisions.</p><p><strong>Methods: </strong>We extracted Differentially expressed genes (DEGs) from the GSE111044 dataset using standard bioinformatics workflows. A network of interacting proteins was assembled to determine hub genes, and TOP2A and CDK1 were selected for immunohistochemical (IHC) validation in 76 SCCE tumor samples. IHC staining scores were analyzed for associations with clinicopathological features. Survival analysis was conducted using Kaplan-Meier estimations and Cox regression modeling to pinpoint independent prognostic factors. To further assess the clinical utility, TOP2A expression was combined with VALSG staging for risk stratification.</p><p><strong>Results: </strong>A comparison between SCCE and adjacent normal tissues revealed 1,202 DEGs. PPI network analysis highlighted two hub genes, TOP2A and CDK1, which IHC validated in 76 SCCE samples. High TOP2A expression was significantly associated with advanced TNM stage (p = 0.020) and deeper tumor invasion (p = 0.004). Multivariate Cox analysis identified high TOP2A expression (HR = 1.92, 95% CI: 1.30-2.82, p = 0.001) and VALSG stage (HR = 2.20, 95% CI: 1.07-4.50, p = 0.031) as independent predictors of prognosis. Time-dependent ROC analysis indicated that the AUCs for the VALSG stage alone were 0.626, 0.638, and 0.602 at 1-, 2-, and 3-year time intervals, respectively. TOP2A alone yielded slightly higher AUCs of 0.719, 0.632, and 0.676. Notably, the combination of TOP2A and VALSG provided the greatest predictive accuracy, achieving AUCs recorded at 0.721, 0.734, and 0.773 at the respective time points.</p><p><strong>Conclusion: </strong>This study suggests that TOP2A is a novel, independent prognostic biomarker in SCCE. When integrated with the VALSG staging system, TOP2A expression enhances risk stratification and may serve as a useful adjunct in clinical prognostication. These findings support its clinical utility while emphasizing the necessity for future studies to include prospective validation.</p>\",\"PeriodicalId\":12465,\"journal\":{\"name\":\"Frontiers in Molecular Biosciences\",\"volume\":\"12 \",\"pages\":\"1640881\"},\"PeriodicalIF\":3.9000,\"publicationDate\":\"2025-07-22\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12321555/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Frontiers in Molecular Biosciences\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.3389/fmolb.2025.1640881\",\"RegionNum\":3,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/1/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q2\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Frontiers in Molecular Biosciences","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.3389/fmolb.2025.1640881","RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/1 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
TOP2A as a prognostic biomarker in small cell carcinoma of the esophagus: an integrated bioinformatics and immunohistochemical study.
Background: Small cell carcinoma of the esophagus (SCCE) is an infrequent but highly aggressive cancer with a poor prognosis. Given its low incidence, there is a lack of validated biomarkers to guide risk stratification and inform treatment decisions.
Methods: We extracted Differentially expressed genes (DEGs) from the GSE111044 dataset using standard bioinformatics workflows. A network of interacting proteins was assembled to determine hub genes, and TOP2A and CDK1 were selected for immunohistochemical (IHC) validation in 76 SCCE tumor samples. IHC staining scores were analyzed for associations with clinicopathological features. Survival analysis was conducted using Kaplan-Meier estimations and Cox regression modeling to pinpoint independent prognostic factors. To further assess the clinical utility, TOP2A expression was combined with VALSG staging for risk stratification.
Results: A comparison between SCCE and adjacent normal tissues revealed 1,202 DEGs. PPI network analysis highlighted two hub genes, TOP2A and CDK1, which IHC validated in 76 SCCE samples. High TOP2A expression was significantly associated with advanced TNM stage (p = 0.020) and deeper tumor invasion (p = 0.004). Multivariate Cox analysis identified high TOP2A expression (HR = 1.92, 95% CI: 1.30-2.82, p = 0.001) and VALSG stage (HR = 2.20, 95% CI: 1.07-4.50, p = 0.031) as independent predictors of prognosis. Time-dependent ROC analysis indicated that the AUCs for the VALSG stage alone were 0.626, 0.638, and 0.602 at 1-, 2-, and 3-year time intervals, respectively. TOP2A alone yielded slightly higher AUCs of 0.719, 0.632, and 0.676. Notably, the combination of TOP2A and VALSG provided the greatest predictive accuracy, achieving AUCs recorded at 0.721, 0.734, and 0.773 at the respective time points.
Conclusion: This study suggests that TOP2A is a novel, independent prognostic biomarker in SCCE. When integrated with the VALSG staging system, TOP2A expression enhances risk stratification and may serve as a useful adjunct in clinical prognostication. These findings support its clinical utility while emphasizing the necessity for future studies to include prospective validation.
期刊介绍：
Much of contemporary investigation in the life sciences is devoted to the molecular-scale understanding of the relationships between genes and the environment — in particular, dynamic alterations in the levels, modifications, and interactions of cellular effectors, including proteins. Frontiers in Molecular Biosciences offers an international publication platform for basic as well as applied research; we encourage contributions spanning both established and emerging areas of biology. To this end, the journal draws from empirical disciplines such as structural biology, enzymology, biochemistry, and biophysics, capitalizing as well on the technological advancements that have enabled metabolomics and proteomics measurements in massively parallel throughput, and the development of robust and innovative computational biology strategies. We also recognize influences from medicine and technology, welcoming studies in molecular genetics, molecular diagnostics and therapeutics, and nanotechnology.
Our ultimate objective is the comprehensive illustration of the molecular mechanisms regulating proteins, nucleic acids, carbohydrates, lipids, and small metabolites in organisms across all branches of life.
In addition to interesting new findings, techniques, and applications, Frontiers in Molecular Biosciences will consider new testable hypotheses to inspire different perspectives and stimulate scientific dialogue. The integration of in silico, in vitro, and in vivo approaches will benefit endeavors across all domains of the life sciences.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
