肺腺癌（LUAD）是癌症死亡的主要原因，许多患者面临着不良预后，特别是那些患有转移性或耐药性肿瘤的患者。同源重组基因 (HRG) 在肿瘤进展和治疗耐药中至关重要，但它们在 LUAD 中的临床意义尚不清楚。在这项研究中，我们系统地描述了 LUAD 患者的关键 HRG，确定了与不同结果和生物功能相关的两种不同的 HR 亚型。我们建立了一个 5 基因评分系统（XRCC2、RAD51、BRCA1、FANCA 和 CHEK1），可以可靠地预测 LUAD 中的患者结果和免疫治疗反应。生物信息学分析和临床验证强调 XRCC2 作为 LUAD 的关键生物标志物。通过体内和体外实验的功能研究揭示了XRCC2在促进肺癌迁移和侵袭中的作用。从机制上讲，XRCC2 通过去泛素化稳定波形蛋白 (VIM) 蛋白的表达。我们预测 c-MYC 作为 XRCC2 的潜在调节剂，并证明用化合物 10058-F4 抑制 c-MYC 会降低 XRCC2 和 VIM 的表达。临床前研究表明，10058-F4 与阿霉素 (Dox) 联合使用时可协同抑制体内转移。我们的研究结果为 LUAD 预后提供了一种潜在的个性化预测工具，将 XRCC2 确定为关键的生物标志物。 c-Myc-XRCC2-VIM 轴成为克服肺转移的有前途的治疗靶点。这项研究为 LUAD 提供了宝贵的见解，提出了一种用于进一步临床验证的预后工具，并揭示了一种通过靶向 c-Myc-XRCC2-VIM 来对抗肺转移的潜在治疗策略。© 2024。作者。

Lung adenocarcinoma (LUAD) is a leading cause of cancer mortality, with many patients facing poor prognosis, particularly those with metastatic or drug-resistant tumors. Homologous recombination genes (HRGs) are crucial in tumor progression and therapy resistance, but their clinical significance in LUAD is not well understood. In this study, we systematically characterize key HRGs in LUAD patients, identifying two distinct HR subtypes associated with different outcomes and biological functions. We establish a 5-gene scoring system (XRCC2, RAD51, BRCA1, FANCA, and CHEK1) that reliably predicts patient outcomes and immunotherapy responses in LUAD. Bioinformatics analysis and clinical validation highlight XRCC2 as a crucial biomarker in LUAD. Functional investigations through in vivo and in vitro experiments reveal the role of XRCC2 in promoting lung cancer migration and invasion. Mechanistically, XRCC2 stabilizes vimentin (VIM) protein expression through deubiquitylation. We predict c-MYC as a potential regulator of XRCC2 and demonstrate that inhibiting c-MYC with compound 10058-F4 reduces XRCC2 and VIM expression. Preclinical studies show the synergistic inhibition of metastasis in vivo when combining 10058-F4 with doxorubicin (Dox). Our findings present a potential personalized predictive tool for LUAD prognosis, identifying XRCC2 as a critical biomarker. The c-Myc-XRCC2-VIM axis emerges as a promising therapeutic target for overcoming lung metastasis. This study provides valuable insights into LUAD, proposing a prognostic tool for further clinical validation and unveiling a potential therapeutic strategy for combating lung metastasis by targeting c-Myc-XRCC2-VIM.© 2024. The Author(s).