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Bioinformatics and Machine Learning-Based Identification of Cell Cycle-Related Genes and Molecular Subtypes in Endometrial Cancer

medrxiv(2024)

Nanchang University Second Affiliated Hospital | Nanchang University

Cited 0|Views5
Abstract
Endometrial cancer is a common malignant tumor in women, with rising incidence rates and an unoptimistic prognosis. DSN1 is a kinetochore protein-coding gene that affects centromere assembly and progression in cell cycles, which is associated with adverse predictions for many cancers. However, the role of DSN1 in UCEC has not yet been reported. We identified the UCEC-related gene module and obtained the differential genes. Then we constructed a diagnostic model and identified the subtype of the molecule and its association with predictions. Subsequently, we identified DSN1 as the core gene and predicted its predictive value. Furthermore, using bioinformatics methods, we found DSN1 was associated with certain clinical characteristics and experimentally validated the expression in cancer tissues of DSN1. Pathway enrichment analysis identified DSN1 as a cell cycle-associated protein, which was validated by WB. The protein interaction network also revealed DSN1 was significantly associated with NDC80. Then we explored the correlation of DSN1 and immune cells and immune cell infiltration and found that DSN1 may affect Th2 enrichment by affecting CCL7 and CCL8. Drug susceptibility analysis showed DSN1 was sensitive to cisplatin and resistant to sunitinib. In conclusion, DSN1 was a novel biomarker that contributes to prognosis and treatment. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement The author(s) received no specific funding for this work. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Not Applicable The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The specimens of all 50 patients from the Second Affiliated Hospital of Nanchang University were pathologically identified with UCEC between December 2023 and September 2024. While the tissues were still fresh, total proteins were removed. The study was approved by the ethics committee of Nanchang University's Second Affiliated Hospital (No. Review [2023] No. (165)). This is a retrospective study. As it analyzed existing medical records and archived samples, obtaining informed consent was infeasible. The ethics committee of Nanchang University's Second Affiliated Hospital has approved the waiver of informed consent for this clinical research. And after the data is collected, information can be obtained that can identify individual participants. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Not Applicable I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Not Applicable I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Not Applicable All datasets in the present study were downloaded from public databases. These public databases allowed researchers to download and analyze public datasets for scientific purposes.
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要点】:本研究通过生物信息学和机器学习方法,确定了DSN1作为子宫内膜癌(UCEC)细胞周期相关基因和分子亚型的核心基因,并探讨了其临床特征、免疫细胞浸润及药物敏感性,为预后和治疗提供了新型生物标志物。

方法】:研究采用生物信息学方法,通过基因模块分析、差异基因识别、诊断模型构建、分子亚型鉴定及相关性预测,最终确定DSN1为核心基因并预测其预后价值。

实验】:实验部分通过对50名患者的UCEC组织进行病理鉴定,并提取新鲜组织中的总蛋白进行验证。数据集来源于公共数据库。通过Western blot(WB)验证了DSN1作为细胞周期相关蛋白的角色,并通过蛋白质相互作用网络分析确认了DSN1与NDC80的显著相关性。研究还探讨了DSN1与免疫细胞及免疫细胞浸润的相关性,并进行了药物敏感性分析,发现DSN1对顺铂敏感,对舒尼替尼耐药。