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

Background: Pulmonary enteric adenocarcinoma (PEAC) is a rare subtype of lung adenocarcinoma. More in-vestigations 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 insta-bility (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 heteroge-neity. 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.

Automated summary

This study found that PEAC has high genetic heterogeneity, and EGFR and ALK inhibitors can effectively treat PEAC. PD-L1 expression and KRAS mutation type may be predictive biomarkers for immunotherapy in PEAC. This study provided both theoretical basis and clinical evidence for PEAC.