Lin Yangui, Li Dan, Hui Hongliang, Miao Haoran, Luo Min, Roy Bhaskar, Chen Binbin, Zhang Wei, Shao Di, Ma Di, Jie Yanbing, Qiu Fan, Li Huaming, Jiang Bo
Department of Thoracic Cardiovascular Surgery, The Eighth Affiliated Hospital of Sun Yat-sen University, Shenzhen, Guangdong, China.
Community Health Center, The Eighth Affiliated Hospital of Sun Yat-sen University, Shenzhen, Guangdong, China.
Front Oncol. 2024 May 13;14:1389618. doi: 10.3389/fonc.2024.1389618. eCollection 2024.
Adenocarcinoma (AIS) and minimally invasive adenocarcinoma (MIA) are considered pre-invasive forms of lung adenocarcinoma (LUAD) with a 5-year recurrence-free survival of 100%. We investigated genomic profiles in early tumorigenesis and distinguished mutational features of preinvasive to invasive adenocarcinoma (IAC) for early diagnosis.
Molecular information was obtained from a 689-gene panel in the 90 early-stage LUAD Chinese patients using next-generation sequencing. Gene signatures were identified between pathology subtypes, including AIS/MIA (n=31) and IAC (n=59) in this cohort. Mutational and clinicopathological information was also obtained from the Cancer Genome Atlas (TCGA) as a comparison cohort.
A higher mutation frequency of , , , , , , , , and was observed in the IAC than in the AIS/MIA group. The AIS/MIA group showed higher mutation frequencies of , , , and . Comparable mutation rates for mutually exclusive genes ( and ) across cohorts highlight the critical transition to invasive LUAD. Compared with the TCGA cohort, , and were frequently mutated in both cohorts. Despite limited gene mutation overlap between cohorts, we observed variant mutation types in invasive LUAD. Additionally, the tumor mutation burden (TMB) values were significantly lower in the AIS/MIA group than in the IAC group in both the Chinese cohort (P=0.0053) and TCGA cohort (P<0.01).
These findings highlight the importance of distinguishing preinvasive from invasive LUAD in the early stages of LUAD and both pathology and molecular features in clinical practice, revealing genomic tumor heterogeneity and population differences.
原位腺癌（AIS）和微浸润腺癌（MIA）被认为是肺腺癌（LUAD）的浸润前形式，其5年无复发生存率为100%。我们研究了早期肿瘤发生中的基因组图谱，并区分了浸润前腺癌与浸润性腺癌（IAC）的突变特征以进行早期诊断。
使用下一代测序从90例中国早期LUAD患者的689基因面板中获取分子信息。在该队列中确定了包括AIS/MIA（n = 31）和IAC（n = 59）在内的病理亚型之间的基因特征。还从癌症基因组图谱（TCGA）获取了突变和临床病理信息作为比较队列。
与AIS/MIA组相比，IAC组中 、 、 、 、 、 、 、 和 的突变频率更高。AIS/MIA组中 、 、 和 的突变频率更高。各队列中互斥基因（ 和 ）的可比突变率突出了向浸润性LUAD的关键转变。与TCGA队列相比， 、 和 在两个队列中均频繁发生突变。尽管各队列之间的基因突变重叠有限，但我们在浸润性LUAD中观察到了变异突变类型。此外，在中国队列（P = 0.0053）和TCGA队列（P < 0.01）中，AIS/MIA组的肿瘤突变负荷（TMB）值均显著低于IAC组。
这些发现突出了在LUAD早期区分浸润前LUAD与浸润性LUAD以及临床实践中病理和分子特征的重要性，揭示了基因组肿瘤异质性和人群差异。
