Li Yuting, Song Chen, Wang Haijun, Di Wenyu, Chen Yangyang, Hu Yuanyuan, Li Peiheng, Chen Jie, Ren Yanfeng, Gong Jing, Wang Qinghua
Department of Radiation Oncology, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, 453100, China.
Department of Hematology Laboratory, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, 453100, China.
Sci Rep. 2025 May 4;15(1):15592. doi: 10.1038/s41598-025-00222-z.
Small cell lung cancer (SCLC) is a highly malignant lung cancer subtype with a dismal prognosis and limited treatment options. This study aimed to identify new prognostic molecular biomarkers for SCLC and explore their immune-related implications for treatment strategies. We analyzed 200 SCLC samples via whole-exome sequencing (WES) and 313 samples by targeted sequencing. A smoking-related SBS4 mutational signature was linked to poorer prognosis and lower tumor mutational burden (TMB), while the APOBEC-mediated SBS13 signature was associated with better prognosis and higher TMB. We identified a molecular subtype with the worst outcomes and lowest TMB in both cohorts. Among 38 high-frequency mutated genes associated with SCLC prognosis, only UNC13A mutations were beneficial. Patients with UNC13A mutations had favorable immune infiltration and tumor immunogenicity. Additionally, TP53 splice site mutations were related to the worst survival outcomes. In conclusion, we discovered new molecular biomarkers for SCLC prognosis. Our findings on their immunological characteristics offer insights for developing novel SCLC treatment strategies.
小细胞肺癌（SCLC）是一种高度恶性的肺癌亚型，预后不佳且治疗选择有限。本研究旨在识别SCLC新的预后分子生物标志物，并探讨其对治疗策略的免疫相关影响。我们通过全外显子组测序（WES）分析了200份SCLC样本，并通过靶向测序分析了313份样本。一种与吸烟相关的SBS4突变特征与较差的预后和较低的肿瘤突变负荷（TMB）相关，而APOBEC介导的SBS13特征与较好的预后和较高的TMB相关。我们在两个队列中均鉴定出了预后最差且TMB最低的分子亚型。在与SCLC预后相关的38个高频突变基因中，只有UNC13A突变是有益的。携带UNC13A突变的患者具有良好的免疫浸润和肿瘤免疫原性。此外，TP53剪接位点突变与最差的生存结果相关。总之，我们发现了SCLC预后的新分子生物标志物。我们对其免疫特征的研究结果为开发新的SCLC治疗策略提供了见解。
