Liu Jinhui, Chen Qi-An, Yang Yannan, Zhang Lin, Lin Weihao, Hong Yuheng, Gao Yibo
Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen 518116, China.
Curr Issues Mol Biol. 2025 May 16;47(5):366. doi: 10.3390/cimb47050366.
Lung adenocarcinoma is the most common NSCLC and is associated with metabolic dysregulation. Purine biosynthesis, regulated by PAICS, plays a key role in tumor progression and therapy resistance.
We focused on LUAD using pan-cancer and KEGG enrichment analyses. TCGA-LUAD and three GEO datasets were analyzed to confirm the prognostic relevance of purine biosynthesis. A prognostic model, the Purine Biosynthesis-Related Score (PBRS), was developed using LASSO regression and validated in independent cohorts. Gene set variation analysis, immune profiling, tumor mutational burden analysis, and drug sensitivity analysis were conducted. PAICS expression was validated in LUAD tissues, and its role was assessed via proliferation and migration assays.
PBRS classified LUAD patients into high-risk (PBRS-high) and low-risk (PBRS-low) subgroups, with distinct prognostic outcomes. PBRS-high patients showed enrichment in cell cycle regulation and DNA repair pathways and had higher TMB, suggesting potential sensitivity to immunotherapy, although immune escape mechanisms may limit the efficacy of immune checkpoint inhibitors. PBRS-low patients were more responsive to metabolic inhibitors. PAICS overexpression correlated with poor prognosis, while its knockdown suppressed LUAD progression.
PBRS is a prognostic tool in LUAD, identifying PBRS-high patients who may benefit from immunotherapy or DDR-targeted therapies. PBRS-low patients exhibit sensitivity to metabolic inhibitors. PAICS is a potential therapeutic target.
肺腺癌是最常见的非小细胞肺癌，与代谢失调相关。由PAICS调节的嘌呤生物合成在肿瘤进展和治疗耐药中起关键作用。
我们使用泛癌和KEGG富集分析聚焦于肺腺癌。分析TCGA-LUAD和三个GEO数据集以确认嘌呤生物合成的预后相关性。使用LASSO回归开发了一种预后模型，即嘌呤生物合成相关评分（PBRS），并在独立队列中进行验证。进行了基因集变异分析、免疫图谱分析、肿瘤突变负荷分析和药物敏感性分析。在肺腺癌组织中验证了PAICS的表达，并通过增殖和迁移试验评估了其作用。
PBRS将肺腺癌患者分为高风险（PBRS高）和低风险（PBRS低）亚组，具有不同的预后结果。PBRS高的患者在细胞周期调节和DNA修复途径中表现出富集，并且具有更高的肿瘤突变负荷，提示对免疫治疗可能敏感，尽管免疫逃逸机制可能会限制免疫检查点抑制剂的疗效。PBRS低的患者对代谢抑制剂更敏感。PAICS的过表达与不良预后相关，而其敲低可抑制肺腺癌进展。
PBRS是肺腺癌的一种预后工具，可识别可能从免疫治疗或DDR靶向治疗中获益的PBRS高的患者。PBRS低的患者对代谢抑制剂敏感。PAICS是一个潜在的治疗靶点。
