肺肠型腺癌（PEAC）是肺腺癌的一种罕见亚型。需要更多的研究关于进一步精准治疗PEAC，以改善预后。该研究招募了24名PEAC患者。对于17名患者，可获取肿瘤组织样本，并进行基于DNA和RNA的下一代测序、PD-L1 IHC染色和基于PCR的微卫星不稳定（MSI）分析。在PEAC中，TP53（70.6％）和KRAS（47.1％）是最常见的突变基因。对于KRAS突变，G12D（37.5％）和G12V（37.5％）的患病率高于G12A（12.5％）和G12C（12.5％）。在94.1％的PEAC患者中鉴定出可操作的受体酪氨酸激酶（包括一个EGFR和两个ALK突变）、PI3K/mTOR、RAS/RAF/MEK、同源重组修复（HRR）和细胞周期信号通路的突变。虽然PD-L1表达在17.6％（3/17）的患者中观察到，但未发现MSI-H患者。转录组数据显示，PD-L1表达阳性的两名患者具有相对较高的免疫浸润。此外，在两名EGFR突变、一名ALK重排和一名PD-L1表达患者中，使用osimertinib、ensartinib和免疫治疗联合化疗可以获得延长的生存期。PEAC是一种遗传异质性疾病，使用EGFR和ALK抑制剂可以有效治疗患者。PD-L1表达和KRAS突变类型可能成为PEAC免疫治疗的预测生物标志物。此研究为PEAC提供了理论和临床证据。版权所有©2023 Elsevier B.V.。保留所有权利。

Pulmonary enteric adenocarcinoma (PEAC) is a rare subtype of lung adenocarcinoma. More investigations about precision therapy in PEAC were required to improve the prognosis.Twenty-four patients with PEAC were enrolled in this study. Tumor tissue samples were available from 17 patients for both DNA and RNA based next-generation sequencing, PD-L1 IHC staining and PCR-based microsatellite instability (MSI) analysis.TP53 (70.6%) and KRAS (47.1%) were the most frequently mutated genes in PEAC. For KRAS mutations, the prevalence of G12D (37.5%) and G12V (37.5%) was higher than G12A (12.5%) and G12C (12.5%). Actionable mutations in receptor tyrosine kinase (including one EGFR and two ALK mutations), PI3K/mTOR, RAS/RAF/MEK, homologous recombination repair (HRR) and cell cycle signaling pathways were identified in 94.1% of patients with PEAC. While PD-L1 expression was observed in 17.6% (3/17) patients, no MSI-H patients were identified. Transcriptomic data showed that two patients with positive PD-L1 expression had relatively high immune infiltration. In addition, prolonged survival was obtained with the treatment of osimertinib, ensartinib, and immunotherapy combined with chemotherapy in two EGFR-mutated, one ALK-rearranged, and one PD-L1 expressed patients, respectively.PEAC is a disease of genetic heterogeneity. The administration of EGFR and ALK inhibitors was effective in patients with PEAC. PD-L1 expression and KRAS mutation type may be used as predictive biomarkers for immunotherapy in PEAC. This study provided both theoretical basis and clinical evidence for PEAC.Copyright © 2023 Elsevier B.V. All rights reserved.