Risk factors including genetic effects are still being investigated in lung adenocarcinoma (LUAD). Mitochondria play an important role in controlling imperative cellular parameters, and anomalies in mitochondrial function might be crucial for cancer development. The mitochondrial genomic aberrations found in lung adenocarcinoma and their associations with cancer development and progression are not yet clearly characterized. Here, we identified a spectrum of mitochondrial genome mutations in early-stage lung adenocarcinoma and explored their association with prognosis and clinical outcomes. Next-generation sequencing was used to reveal the mitochondrial genomes of tumor and conditionally normal adjacent tissues from 61 Stage 1 LUADs. Mitochondrial somatic mutations and clinical outcomes including relapse-free survival (RFS) were analyzed. Patients with somatic mutations in the D-loop region had longer RFS (adjusted hazard ratio, adjHR = 0.18, p = 0.027), whereas somatic mutations in mitochondrial Complex IV and Complex V genes were associated with shorter RFS (adjHR = 3.69, p = 0.012, and adjHR = 6.63, p = 0.002, respectively). The risk scores derived from mitochondrial somatic mutations were predictive of RFS (adjHR = 9.10, 95%CI: 2.93–28.32, p < 0.001). Our findings demonstrated the vulnerability of the mitochondrial genome to mutations and the potential prediction ability of somatic mutations. This research may contribute to improving molecular guidance for patient treatment in precision medicine.

中文翻译：

---

第一期肺腺癌的线粒体基因组景观和临床结果

肺腺癌 (LUAD) 的危险因素（包括遗传效应）仍在研究中。线粒体在控制必要的细胞参数中发挥着重要作用，线粒体功能的异常可能对癌症的发展至关重要。肺腺癌中发现的线粒体基因组畸变及其与癌症发生和进展的关系尚未明确表征。在这里，我们鉴定了早期肺腺癌中的一系列线粒体基因组突变，并探讨了它们与预后和临床结果的关系。使用下一代测序揭示了来自 61 个 1 期 LUAD 的肿瘤和条件正常邻近组织的线粒体基因组。分析了线粒体体细胞突变和临床结果，包括无复发生存期（RFS）。D 环区域发生体细胞突变的患者具有较长的 RFS（调整后的风险比，adjHR = 0.18，p = 0.027），而线粒体复合物 IV 和复合物 V 基因的体细胞突变与较短的 RFS 相关（adjHR = 3.69，p = 0.012，adjHR = 6.63，p = 0.002，分别）。源自线粒体体细胞突变的风险评分可预测 RFS（adjHR = 9.10，95% CI：2.93–28.32，p < 0.001）。我们的研究结果证明了线粒体基因组对突变的脆弱性以及体细胞突变的潜在预测能力。这项研究可能有助于改善精准医学中患者治疗的分子指导。