Department of Pathology, Hanyang University Guri Hospital, Hanyang University College of Medicine, Guri, Gyeonggi-do, 11923, Republic of Korea.
Sci Rep. 2021 Jan 14;11(1):1321. doi: 10.1038/s41598-020-79907-6.
The histological classification of lung adenocarcinoma includes 5 types: lepidic, acinar, papillary, micropapillary and solid. The complex gene interactions and anticancer immune response of these types are not well known. The aim of this study was to reveal the survival rates, genetic alterations and immune activities of the five histological types and provide treatment strategies. This study reviewed the histological findings of 517 patients with lung adenocarcinoma from The Cancer Genome Atlas (TCGA) database and classified them into five types. We performed gene set enrichment analysis (GSEA) and survival analysis according to the different types. We found six oncogenic gene sets that were higher in lung adenocarcinoma than in normal tissues. In the survival analysis of each type, the acinar type had a favorable prognosis, and the solid subtype had an unfavorable prognosis; however, the survival differences between the other types were not significant. Our study focused on the solid type, which had the poorest prognosis. The solid type was related to adaptive immune resistance associated with elevated CD8 T cells and high CD274 (encoding PD-L1) expression. In the pathway analyses, the solid type was significantly related to high vascular endothelial growth factor (VEGF)-A expression, reflecting tumor angiogenesis. Non-necrosis/low immune response affected by high VEGF-A was associated with worse prognosis. The solid type associated with high VEGF-A expression may contribute to the development of therapeutic strategies for lung adenocarcinoma.
肺腺癌的组织学分类包括 5 种类型：贴壁型、腺泡型、乳头状、微乳头型和实体型。这些类型的复杂基因相互作用和抗癌免疫反应尚不清楚。本研究旨在揭示五种组织学类型的生存率、遗传改变和免疫活性，并提供治疗策略。本研究回顾了来自癌症基因组图谱（TCGA）数据库的 517 例肺腺癌患者的组织学发现，并将其分为 5 种类型。我们根据不同类型进行了基因集富集分析（GSEA）和生存分析。我们发现了六个在肺腺癌中高于正常组织的致癌基因集。在每种类型的生存分析中，腺泡型预后良好，实体型预后不良；然而，其他类型之间的生存差异不显著。我们的研究集中在预后最差的实体型上。实体型与适应性免疫抵抗有关，与 CD8 T 细胞升高和 CD274（编码 PD-L1）表达升高有关。在通路分析中，实体型与高血管内皮生长因子（VEGF）-A 表达显著相关，反映了肿瘤血管生成。非坏死/高免疫反应受高 VEGF-A 影响与预后较差相关。与高 VEGF-A 表达相关的实体型可能有助于制定肺腺癌的治疗策略。
