The detailed analysis results of cancer grading.

The study explores the prognostic significance and therapeutic potential of 3-phosphoinositide dependent protein kinase-1 (PDK1) in osteosarcoma. Using bioinformatics analysis and experimental validation, we analyzed PDK1 expression and its correlation with patient prognosis from GEPIA and UCSCXena databases. High PDK1 expression was found to be significantly associated with reduced survival in osteosarcoma patients, suggesting its value as a prognostic biomarker. Functional assays were performed to investigate the biological processes influenced by PDK1. Gene Ontology (GO) analysis indicated that PDK1 is involved in metabolism and cell proliferation. KEGG enrichment analysis revealed that genes related to PDK1 are enriched in pathways associated with metabolism, cell proliferation, and immune escape. In vitro experiments demonstrate that silencing PDK1 impairs glycolysis, reduces proliferation, and induces apoptosis in 143B osteosarcoma cells. Pan-cancer analysis confirms PDK1’s overexpression and poor prognosis association in multiple malignancies. Pan-cancer analysis extended the findings to other cancer types, confirming that PDK1 is overexpressed in multiple malignancies and generally associated with poor prognosis. This reinforces the potential of PDK1 as a universal biomarker and therapeutic target in oncology. The findings suggest PDK1 as a critical regulator of glycolytic metabolism and a potential therapeutic target in osteosarcoma. Targeting PDK1 could provide a novel therapeutic strategy for treating osteosarcoma and possibly other cancers.

本研究探讨了3-磷酸肌醇依赖性蛋白激酶-1（3-phosphoinositide dependent protein kinase-1，PDK1）在骨肉瘤中的预后价值与治疗潜力。本研究借助生物信息学分析与实验验证，从GEPIA及UCSCXena数据库中分析了PDK1的表达水平及其与患者预后的相关性。研究发现，PDK1高表达与骨肉瘤患者的生存期缩短显著相关，提示其可作为预后生物标志物。为探究PDK1调控的生物学过程，本研究开展了功能实验：基因本体（Gene Ontology，GO）分析表明，PDK1参与代谢过程与细胞增殖调控；京都基因与基因组百科全书（Kyoto Encyclopedia of Genes and Genomes，KEGG）富集分析显示，PDK1相关基因富集于代谢、细胞增殖及免疫逃逸相关通路。体外实验证实，敲低PDK1可抑制143B骨肉瘤细胞的糖酵解过程、降低细胞增殖能力并诱导细胞凋亡。泛癌分析验证了PDK1在多种恶性肿瘤中的过表达现象及其与不良预后的关联，且进一步将研究结论拓展至其他癌种，证实PDK1在多种恶性肿瘤中均存在过表达，且普遍与不良预后相关。这进一步强化了PDK1作为肿瘤学领域通用生物标志物与治疗靶点的潜力。本研究结果表明，PDK1是糖酵解代谢的关键调控因子，同时也是骨肉瘤潜在的治疗靶点；靶向PDK1可为骨肉瘤乃至其他恶性肿瘤的治疗提供全新策略。