肺癌切除后的疾病预后可能受到病理亚型的影响。在本研究中，我们研究了原位腺癌（AIS）/微浸润腺癌（MIA）和浸润性腺癌（IAC）亚型之间基因变异的差异和显着改变的通路，以揭示预后差异的分子机制。对61个肿瘤组织进行了研究到DNA提取和定制136个基因靶向下一代测序。组间比较采用分类变量的双侧Fisher精确检验和数值变量的双尾不配对t检验。所有样本中共检测到涉及70个基因的402个体细胞突变，其中74.29%的基因发生突变。至少有两个样本发生突变。 PMS2、ARID1A、EGFR 和 POLE 是最常见的突变基因。在一名 IAC 患者中观察到 ALK_EML4 融合，在一名 AIS 患者中观察到 RET_KIF5B 融合。 IAC组中TP53基因突变的患者比例显着较高（P = 0.0057）。 IAC组的平均发病年龄为62.48岁，高于其他亚型（P = 0.0166）。结果表明，mTOR信号通路（56.52% vs 26.32%，P = 0.0288）和Hippo信号通路（34.78% vs 10.53%，P = 0.0427）相关基因突变在IAC亚型中显着富集，表明IAC亚型中的关键参与基因突变mTOR 和 Hippo 信号通路在肺癌发生和恶性进展中的作用。这项研究揭示了不同肺癌亚型之间基因突变的异质性和显着改变的通路，提示了不同预后的潜在机制。© 2023。作者，独家Springer Science Business Media, LLC（Springer Nature 的一部分）的许可。

Disease prognosis after resection of lung cancer could be affected by pathological subtypes. In this study, we investigated the difference of gene variation and significantly altered pathways between adenocarcinoma in situ (AIS)/microinvasive adenocarcinoma (MIA) and invasive adenocarcinoma (IAC) subtypes to reveal the molecular mechanism of prognosis differences.Sixty one tumor tissues were subjected to DNA extraction and customized 136 gene targeted next-generation sequencing. Comparisons between groups were performed with two-sided Fisher's exact test for categorical variables and two-tailed unpaired t test for numerical variables.A total of 402 somatic mutations involved in 70 genes were detected in all these samples, and 74.29% of these genes were mutated in at least two samples. PMS2, ARID1A, EGFR, and POLE were the most frequently mutated genes. ALK_EML4 fusion was observed in one IAC patient and RET_ KIF5B fusion in one AIS patient. A significant higher proportion of patients with TP53 gene mutation was observed in the IAC group (P = 0.0057). The average onset age in IAC group is 62.48 years, which is greater than other subtypes (P = 0.0166). It revealed that mutations in genes involved in the mTOR signaling pathway (56.52% vs 26.32%, P = 0.0288) and Hippo signaling pathway (34.78% vs 10.53%, P = 0.0427) were significantly enriched in IAC subtypes, suggesting the key involvement of mTOR and Hippo signaling pathways in lung tumor development and malignant progression.This study revealed the heterogeneity of gene mutations and significantly altered pathways between different lung cancer subtypes, suggesting the potential mechanism of different prognosis.© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.