Meng Fanchen, Zhang Yi, Wang Siwei, Liu Tongyan, Sun Mengting, Zhu Hongyu, Dong Guozhang, Xia Zhijun, You Jing, Kong Xiangru, Wu Jintao, Chen Peng, Yuan Fangwei, Yu Xinyu, Xu Youtao, Xu Lin, Yin Rong
Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Department of Thoracic Surgery, Jiangsu Cancer Hospital & Nanjing Medical University Affiliated Cancer Hospital & Jiangsu Institute of Cancer Research, Nanjing 210009, China.
Department of Pathology, Jiangsu Cancer Hospital & Nanjing Medical University Affiliated Cancer Hospital & Jiangsu Institute of Cancer Research, Nanjing 210009, China.
Cancers (Basel). 2022 Aug 27;14(17):4165. doi: 10.3390/cancers14174165.
Micropapillary components are observed in a considerable proportion of ground-glass opacities (GGOs) and contribute to the poor prognosis of patients with invasive lung adenocarcinoma (LUAD). However, the underlying mutational processes related to the presence of micropapillary components remain obscure, limiting the development of clinical interventions.
We collected 31 GGOs, which were separated into paired micropapillary and non-micropapillary components using microdissection. Whole-exome sequencing (WES) was performed on the GGO components, and bioinformatics analysis was conducted to reveal the genomic features of the micropapillary component in invasive LUAD.
The micropapillary component had more genomic variations, including tumor mutation burden, intratumoral heterogeneity, and copy number variation. We also observed the enrichment of AID/APOBEC mutation signatures and an increased activation of the RTK/Ras, Notch, and Wnt oncogenic pathways within the micropapillary component. A phylogenetic analysis further suggested that ERBB2/3/4, NCOR1/2, TP53, and ZNF469 contributed to the micropapillary component's progression during the early invasion of LUAD, a finding that was validated in the TCGA cohort.
Our results revealed specific mutational characteristics of the micropapillary component of invasive LUAD in an Asian population. These characteristics were associated with the formation of high-grade invasive patterns. These preliminary findings demonstrated the potential of targeting the micropapillary component in patients with early-stage LUAD.
在相当比例的磨玻璃影（GGO）中观察到微乳头成分，其与浸润性肺腺癌（LUAD）患者的不良预后相关。然而，与微乳头成分存在相关的潜在突变过程仍不清楚，这限制了临床干预措施的发展。
我们收集了31个GGO，通过显微切割将其分离为配对的微乳头和非微乳头成分。对GGO成分进行全外显子组测序（WES），并进行生物信息学分析以揭示浸润性LUAD中微乳头成分的基因组特征。
微乳头成分具有更多的基因组变异，包括肿瘤突变负荷、肿瘤内异质性和拷贝数变异。我们还观察到微乳头成分中AID/APOBEC突变特征的富集以及RTK/Ras、Notch和Wnt致癌途径的激活增加。系统发育分析进一步表明，ERBB2/3/4、NCOR1/2、TP53和ZNF469在LUAD早期侵袭过程中促进了微乳头成分的进展，这一发现在TCGA队列中得到了验证。
我们的结果揭示了亚洲人群中浸润性LUAD微乳头成分的特定突变特征。这些特征与高级别侵袭模式的形成有关。这些初步发现证明了针对早期LUAD患者微乳头成分的潜力。
