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Molecular differences across invasive lung adenocarcinoma morphological subgroups.

ABSTRACT: 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.

SUBMITTER: Ci B

PROVIDER: S-EPMC7481608 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Molecular differences across invasive lung adenocarcinoma morphological subgroups.

Ci Bo B Yang Donghan M DM Cai Ling L Yang Lin L Girard Luc L Fujimoto Junya J Wistuba Ignacio I II Xie Yang Y Minna John D JD Travis William W Xiao Guanghua G

Translational lung cancer research 20200801 4

<h4>Background</h4>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. ...[more]

PMID: 32953482

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Project description:BackgroundSex-related differences in cancer epidemiology, tumor biology, immune system activity, and pharmacogenomics have been suggested to be important considerations for precision cancer control. Here we elucidated systematically sex biases in genetic variants, gene expression profiles, and immunological landscapes of lung adenocarcinoma patients (LUADs) with different ancestry and smoking status.MethodsSomatic mutation and mRNA expression data of Asian and Non-Asian LUADs were obtained from public databases. Sex-biased genetic mutations, gene expression, biological pathways, and immune infiltration were identified in the context of smoking status and race.ResultsAmong nonsmokers, male-biased mutations were prevalent in Asian LUADs, while few sex-biased mutations were detected in Non-Asian LUADs. EGFR was the only mutation whose frequency was significantly higher in females than males in both Asian and Non-Asian nonsmokers. More genes exhibited sex-biased expression in Non-Asian LUADs compared to Asian LUADs. Moreover, genes distinctly expressed in females were mainly related to immune-related pathways, whereas those in males were more involved in activation of DNA repair, E2F_targets, and MYC_targets pathways. We also detected sex-specific immune infiltration in the context of genetic variation. In EGFR-mutant LUADs, males had a significantly increased infiltration of CD8 + T cells, whereas resting CD4 + memory T cells were more abundant in females. Additionally, in KRAS-mutant LUADs, CD8 + and CD4 + T cells were more abundant in females than males. In addition, we detected all female patients with high SCGB3A2 expression were exclusively sensitive to immunotherapy, while this phenomenon was not observed in male patients.ConclusionsOur findings provided evidence that sex-related molecular and cellular components are involved in shaping tumor distinct genetic and immune features, which might have important impact on personalized targeted and immune therapy.

Dataset Information

Molecular differences across invasive lung adenocarcinoma morphological subgroups.

Publications

Molecular differences across invasive lung adenocarcinoma morphological subgroups.

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