针对运动相关基因和胎盘生长因子用于头颈鳞状细胞癌的治疗开发。
Targeting exercise-related genes and placental growth factor for therapeutic development in head and neck squamous cell carcinoma.
发表日期:2024
作者:
Qingyuan Shi, Haiyue Ying, Weibin Weng
来源:
Frontiers in Pharmacology
摘要:
人类癌症,包括头颈鳞状细胞癌 (HNSCC),是由不受控制的细胞生长和增殖驱动的复杂且异质的疾病。蛋白质的翻译后修饰 (PTM) 在癌症进展中发挥着至关重要的作用,使其成为药物干预的有希望的目标。本研究旨在通过综合生物信息学分析,识别对 HNSCC 具有预后价值的关键运动相关基因,特别关注胎盘生长因子 (PIGF) 的治疗潜力。HNSCC 的转录组数据来自癌症基因组图谱 (TCGA)数据库。鉴定出差异表达基因(DEG)并分析其预后意义。从基因集富集分析(GSEA)数据库中检索与运动相关的基因集。进行了功能富集分析,包括基因本体论 (GO)、京都基因和基因组百科全书 (KEGG) 和 GSEA。通过单基因表达分析、免疫浸润分析和体外细胞实验,进一步探讨关键基因的生物学功能和临床意义。该研究鉴定了与头颈部鳞癌生存预后相关的运动相关基因。 GO 和 KEGG 通路分析强调了这些基因的生物学功能,Kaplan-Meier 生存曲线证实了它们的预后价值。使用 TCGA 数据进行 PIGF 表达分析显示了其诊断潜力,较高的表达与晚期肿瘤阶段相关。单细胞测序揭示了 PIGF 在肿瘤微环境中的作用。体外实验表明,PIGF 在增强 HNSCC 细胞增殖和集落形成方面发挥着关键作用,PIGF 敲低会显着损害这些功能,凸显了其在肿瘤生长调节中的重要性。此外,PIGF 在整个癌症数据集中的药物敏感性预测性能表明其作为药理学靶点的潜力,为调节免疫微环境和改善癌症治疗的治疗结果提供了机会。这项研究为 HNSCC 的分子机制提供了新的见解,并确定了与运动相关的分子机制。基因,特别是 PIGF,作为临床治疗和个性化医疗的有前途的生物标志物。通过关注 PTM 及其在癌症进展中的作用,我们的研究结果表明,靶向 PIGF 可能提供创新的治疗策略。版权所有 © 2024 Shi、Ying 和 Weng。
Human cancers, including head and neck squamous cell carcinoma (HNSCC), are complex and heterogeneous diseases driven by uncontrolled cell growth and proliferation. Post-translational modifications (PTMs) of proteins play a crucial role in cancer progression, making them a promising target for pharmacological intervention. This study aims to identify key exercise-related genes with prognostic value in HNSCC through comprehensive bioinformatics analysis, with a particular focus on the therapeutic potential of placental growth factor (PIGF).Transcriptome data for HNSCC were obtained from The Cancer Genome Atlas (TCGA) database. Differently expressed genes (DEGs) were identified and analyzed for their prognostic significance. Exercise-related gene sets were retrieved from the Gene Set Enrichment Analysis (GSEA) database. Functional enrichment analyses, including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and GSEA, were conducted. The biological functions and clinical implications of key genes were further explored through single-gene expression analysis, immune infiltration analysis, and in vitro cellular experiments.The study identified exercise-related genes associated with survival prognosis in HNSCC. GO and KEGG pathway analyses highlighted the biological functions of these genes, and Kaplan-Meier survival curves confirmed their prognostic value. PIGF expression analysis using TCGA data showed its diagnostic potential, with higher expression linked to advanced tumor stages. Single-cell sequencing revealed PIGF's role in the tumor microenvironment. In vitro experiments demonstrated that PIGF plays a pivotal role in enhancing cell proliferation and colony formation in HNSCC, with PIGF knockdown significantly impairing these functions, highlighting its importance in tumor growth regulation. Additionally, PIGF's predictive performance in drug sensitivity across cancer datasets suggests its potential as a pharmacological target, offering opportunities to modulate the immune microenvironment and improve therapeutic outcomes in cancer treatment.This study provides new insights into the molecular mechanisms underlying HNSCC and identifies exercise-related genes, particularly PIGF, as promising biomarkers for clinical treatment and personalized medicine. By focusing on PTMs and their role in cancer progression, our findings suggest that targeting PIGF may offer innovative therapeutic strategies.Copyright © 2024 Shi, Ying and Weng.