Genomic Landscape and Immune Microenvironment Features of Preinvasive and Early Invasive Lung Adenocarcinoma
| Autor: | Wen-Zhao Zhong, X.-N. Yang, Zhi Li, Qing Zhou, Jianjun Zhang, Chao Zhang, Jian Su, X. Zhang, Jin Ji Yang, Yi-Long Wu, Yang Shao, Yin Guang Wang, Song Dong, Fang Ping Xu, Qiang Nie, Zhi Xie |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Pulmonary and Respiratory Medicine Neuroblastoma RAS viral oncogene homolog Male Lung Neoplasms Adenocarcinoma of Lung Adenocarcinoma in Situ medicine.disease_cause Receptor tyrosine kinase Article Metastasis Clonal Evolution Cohort Studies 03 medical and health sciences 0302 clinical medicine Biomarkers Tumor Tumor Microenvironment Medicine Humans Neoplasm Invasiveness Exome sequencing biology business.industry Genomics medicine.disease 030104 developmental biology Oncology Immunoediting 030220 oncology & carcinogenesis Mutation Cancer research biology.protein Adenocarcinoma Immunohistochemistry Female business Carcinogenesis Carcinoma in Situ |
| Zdroj: | Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer. 14(11) |
| ISSN: | 1556-1380 |
| Popis: | Background Understanding the genomic landscape and immune microenvironment features of preinvasive and early invasive lung adenocarcinoma may provide critical insight and facilitate development of novel strategies for early detection and intervention. Methods A total of 80 tumor tissue samples and 30 paired histologically normal lung tissue samples from 30 patients with adenocarcinoma in situ (AIS) (n = 8), minimally invasive adenocarcinoma (MIA) (n = 8), and invasive adenocarcinoma (IAC) (n = 14) were subjected to multiregion whole exome sequencing and immunohistochemistry staining for CD8 and programmed death ligand 1 (PD-L1). Results All tumors, including AIS, exhibited evidence of genomic intratumor heterogeneity. Canonical cancer gene mutations in EGFR, erb-b2 receptor tyrosine kinase 2 gene (ERBB2), NRAS, and BRAF were exclusively trunk mutations detected in all regions within each tumor, whereas genes associated with cell mobility, gap junction, and metastasis were all subclonal mutations. EGFR mutation represented the most common driver alterations across AIS, MIA, and IAC, whereas tumor protein p53 gene (TP53) was identified in MIA and IAC but not in AIS. There was no difference in PD-L1 expression among AIS, MIA, and IAC, but the CD8 positivity rate was higher in IAC. Tumors positive for both PD-L1 and CD8 had a larger proportion of subclonal mutations. Conclusions Mutations in EGFR, ERBB2, NRAS, and BRAF are early clonal genomic events during carcinogenesis of lung adenocarcinoma, whereas TP53 and cell mobility, gap junction, and metastasis-related genes may be late events associated with subclonal diversification and neoplastic progression. Genomic intratumor heterogeneity and immunoediting are common and early phenomena that may have occurred before the acquisition of invasion. |
| Databáze: | OpenAIRE |
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