Department of Thoracic Oncology, Osaka International Cancer Institute, Osaka, Japan.
Genome Analysis Center, Yamanashi Central Hospital, Yamanashi, Japan.
Thorac Cancer. 2023 Aug;14(22):2210-2215. doi: 10.1111/1759-7714.15038. Epub 2023 Jul 13.
In this study, we investigated the association between PD-L1 expression in tumor cells and underlying genetic mutations, which was analyzed in detail using laser microdissection and next-generation sequencing analysis. To investigate whether driver mutations are involved in the background of PD-L1 expression, the EGFR major activating mutation was selected as the most frequent driver mutation. Surgical resection specimens were used to extract sufficient amounts of nucleic acids for analysis, and the high tumor proportion score (TPS:100%) and low (TPS: 0%) PD-L1-expressing parts of the tumor were each laser microdissected to examine the association between PD-L1 expression heterogeneity and genetic mutations within the same tumor. The association between PD-L1 heterogeneity and gene mutations within the same tumor was investigated. Analysis showed no association between PD-L1 expression heterogeneity and genetic variants, which were found to be almost identical. However, PD-L1 expression was found to be associated with the number of tumor infiltrating lymphocytes (TILs) present in the tumor, which may be related to whether or not lymphocytes can infiltrate into the tumor depending on the tumor histological type (solid pattern, lepidic pattern, etc.) and other factors.
在这项研究中，我们研究了肿瘤细胞中 PD-L1 表达与潜在遗传突变之间的关系，我们使用激光微切割和下一代测序分析对其进行了详细分析。为了研究驱动突变是否参与 PD-L1 表达的背景，选择 EGFR 主要激活突变为最常见的驱动突变。使用手术切除标本提取足够量的核酸进行分析，并对肿瘤的高肿瘤比例评分（TPS：100%）和低（TPS：0%）PD-L1 表达部分进行激光微切割，以检查同一肿瘤内 PD-L1 表达异质性与遗传突变之间的关联。研究了 PD-L1 异质性与同一肿瘤内基因突变之间的关系。分析表明，PD-L1 表达异质性与遗传变异之间没有关联，它们几乎完全相同。然而，PD-L1 表达与肿瘤浸润淋巴细胞（TILs）的数量有关，这可能与肿瘤的组织学类型（实体模式、苔癣模式等）和其他因素有关，决定了淋巴细胞是否能够浸润到肿瘤中。
