Molecular differences across invasive lung adenocarcinoma morphological subgroups

Background: Lung adenocarcinomas (ADCs) show heterogeneous morphological patterns that are classified into five subgroups: lepidic predominant, papillary predominant, acinar predominant, micropapillary predominant and solid predominant. The morphological classification of ADCs has been reported to be associated with patient prognosis and adjuvant chemotherapy response. However, the molecular mechanisms underlying the morphology differences among different subgroups remain largely unknown. Methods: Using the molecular profiling data from The Cancer Genome Atlas (TCGA) lung ADC (LUAD) cohort, we studied the molecular differences across invasive ADC morphological subgroups. Results: We showed that the expression of proteins and mRNAs, but not the gene mutations copy number alterations (CNA), were significantly associated with lung ADC morphological subgroups. In addition, expression of the FOXM1 gene (which is negatively associated with patient survival) likely plays an important role in the morphological differences among different subgroups. Moreover, we found that protein abundance of PD-L1 were associated with the malignancy of subgroups. These results were validated in an independent cohort. Conclusions: This study provides insights into the molecular differences among different lung ADC morphological subgroups, which could lead to potential subgroup-specific therapies.