PARP inhibitors can be used to treat solid tumors that often have mutations in important homologous recombination (HR) genes, such as BRCA1/2. While other kinds of tumors could also experience HR deficiencies, including those associated with lung cancer, there is little information on the frequency of these occurrences. Homologous recombination deficiency (HRD) was used to induce particular DNA aberration profiles and related transcriptome alterations. Their presence can identify whether an HR deficiency is present or absent in a particular tumor sample, even without observed HR gene changes. From whole-exome sequencing data in lung adenocarcinoma obtained from TCGA, we obtained several mutational signatures associated with HRD and determined that these HRD-associated mutational signatures are related to genomic installability. We then constructed a prediction model, which found that 11 genes associated with HRD scores could be used as predictors of survival outcomes in LUAD patients. These genes are related to PI3K-Akt, T cell receptors, and the Chemokine pathway. Other GEO datasets validated the survival prediction, which was independent of the PD1/PDL1 treatment. Collectively, our study provides transcriptome biomarkers of lung adenocarcinoma complementary to the HRD score and introduces a novel method of identifying prognostic biomarkers of immunotherapy.

PARP 抑制剂可用于治疗在重要的同源重组 (HR) 基因中经常发生突变的实体瘤，例如 BRCA1/2。虽然其他类型的肿瘤也可能出现 HR 缺陷，包括与肺癌相关的那些，但关于这些发生频率的信息很少。同源重组缺陷 (HRD) 用于诱导特定的 DNA 畸变谱和相关的转录组改变。它们的存在可以识别特定肿瘤样本中是否存在 HR 缺陷，即使没有观察到 HR 基因变化。从 TCGA 获得的肺腺癌的全外显子组测序数据中，我们获得了几个与 HRD 相关的突变特征，并确定这些与 HRD 相关的突变特征与基因组可安装性有关。然后，我们构建了一个预测模型，发现与 HRD 评分相关的 11 个基因可用作 LUAD 患者生存结果的预测因子。这些基因与 PI3K-Akt、T 细胞受体和趋化因子途径有关。其他 GEO 数据集验证了独立于 PD1/PDL1 治疗的生存预测。总的来说，我们的研究提供了与 HRD 评分互补的肺腺癌转录组生物标志物，并介绍了一种识别免疫治疗预后生物标志物的新方法。这与 PD1/PDL1 治疗无关。总的来说，我们的研究提供了与 HRD 评分互补的肺腺癌转录组生物标志物，并介绍了一种识别免疫治疗预后生物标志物的新方法。这与 PD1/PDL1 治疗无关。总的来说，我们的研究提供了与 HRD 评分互补的肺腺癌转录组生物标志物，并介绍了一种识别免疫治疗预后生物标志物的新方法。