Genomic and transcriptomic insights into the precision treatment of pulmonary enteric adenocarcinoma

Abstract

BackgroundPulmonary enteric adenocarcinoma (PEAC) is a rare subtype of lung adenocarcinoma. More investigations about precision therapy in PEAC were required to improve the prognosis. Methods: 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. Results: 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. Conclusion: 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.