DataSheet_2_Comprehensive Comparative Molecular Characterization of Young and Old Lung Cancer Patients.pdf

BackgroundYoung lung cancer as a small subgroup of lung cancer has not been fully studied. Most of the previous studies focused on the clinicopathological features, but studies of molecular characteristics are still few and limited. Here, we explore the characteristics of prognosis and variation in young lung cancer patients with NSCLC.
MethodsA total of 5639 young lung cancer samples (NSCLC, age ≤40) were screened from the SEER and the same number of the old (NSCLC, age ≥60) were screened by propensity score matching to evaluate the prognosis of two groups. 165 treatment-naïve patients diagnosed with NSCLC were enrolled to explore the molecular feature difference between two age-varying groups. CCLE cell line expression data was used to verify the finding from the cohort of 165 patients.
ResultsThe overall survival of the young lung cancer group was significantly better than the old. Germline analysis showed a trend that the young group contained a higher incidence of germline alterations. The TMB of the young group was lower. Meanwhile, the heterogeneity and evolutionary degrees of the young lung cancer group were also lower than the old. The mutation spectrums of two groups exhibited variance with LRP1B, SMARCA4, STK11, FAT2, RBM10, FANCM mutations, EGFR L858R more recurrent in the old group and EML4-ALK fusions, BCL2L11 deletion polymorphism, EGFR 19DEL, 20IN more recurrent in the young group. For the base substitution, the young showed a lower fraction of transversion. Further, we performed a pathway analysis and found the EGFR tyrosine kinase inhibitor resistance pathway enriched in the young lung cancer group, which was validated in gene expression data later.
ConclusionsThere were significantly different molecular features of the young lung cancer group. The young lung cancer group had a more simple alteration structure. Alteration spectrums and base substitution types varied between two groups, implying the different pathogenesis. The young lung cancer group had more potential treatment choices. Although young lung patients had better outcomes, there were still adverse factors of them, suggesting that the young group still needs more caution for treatment choice and monitoring after the treatment to further improve the prognosis.

背景：青年肺癌作为肺癌的小众亚型，尚未得到充分研究。既往多数研究聚焦于其临床病理特征，而分子特征相关研究仍较为匮乏且有限。本研究旨在探索青年非小细胞肺癌（Non-Small Cell Lung Cancer, NSCLC）患者的预后特征及变异情况。
方法：本研究从SEER（监测、流行病学与最终结果数据库）数据库中筛选出5639例青年肺癌样本（非小细胞肺癌，年龄≤40岁），并通过倾向得分匹配法匹配出相同数量的老年非小细胞肺癌样本（年龄≥60岁），以评估两组患者的预后情况。另纳入165例初治确诊的非小细胞肺癌患者，用于探究不同年龄组之间的分子特征差异。本研究采用CCLE（癌症细胞系百科全书，Cancer Cell Line Encyclopedia）细胞系表达数据，对165例患者队列的研究结果进行验证。
结果：青年肺癌组的总生存期显著优于老年组。生殖系分析显示，青年组的生殖系变异发生率呈升高趋势。青年组的肿瘤突变负荷（Tumor Mutational Burden, TMB）更低。同时，青年肺癌组的肿瘤异质性及进化程度也低于老年组。两组的突变谱存在差异：LRP1B、SMARCA4、STK11、FAT2、RBM10、FANCM突变及EGFR L858R突变在老年组中更为常见；而EML4-ALK融合基因、BCL2L11缺失多态性、EGFR 19号外显子缺失（19DEL）及20号外显子插入（20IN）在青年组中更为频发。在碱基替换方面，青年组的颠换比例更低。进一步的通路分析显示，青年肺癌组富集EGFR酪氨酸激酶抑制剂耐药通路，该结果后续通过基因表达数据得到验证。
结论：青年肺癌患者存在显著不同的分子特征。青年肺癌组的变异结构更为简洁。两组的变异谱及碱基替换类型存在差异，提示其发病机制有所不同。青年肺癌组拥有更多潜在治疗选择。尽管青年肺癌患者的预后更佳，但仍存在不良预后因素，这表明青年患者在治疗选择及治疗后监测方面仍需更加谨慎，以进一步改善其预后。