Abstract
We previously showed that different pathologic subtypes were associated with different prognostic values in patients with stage IA lung adenocarcinoma (AC). We hypothesize that differential gene expression profiles of different subtypes may be valuable factors for prognosis in stage IA lung adenocarcinoma. We performed microarray gene expression profiling on tumor tissues micro-dissected from patients with acinar and solid predominant subtypes of stage IA lung adenocarcinoma. These patients had undergone a lobectomy and mediastinal lymph node dissection at the Shanghai Chest Hospital, Shanghai, China in 2012. No patient had preoperative treatment. We performed the Gene Set Enrichment Analysis (GSEA) analysis to look for gene expression signatures associated with tumor subtypes. The histologic subtypes of all patients were classified according to the 2015 WHO lung Adenocarcinoma classification. We found that patients with the solid predominant subtype are enriched for genes involved in RNA polymerase activity as well as inactivation of the p53 pathway. Further, we identified a list of genes that may serve as prognostic markers for stage IA lung adenocarcinoma. Validation in the TCGA database shows that these genes are correlated with survival, suggesting that they are novel prognostic factors for stage IA lung adenocarcinoma. In conclusion, we have uncovered novel prognostic factors for stage IA lung adenocarcinoma using gene expression profiling in combination with histopathology subtyping.
Highlights
Lung cancer is the leading cause of cancer related death worldwide [1] and adenocarcinoma (AC) is the most common histological type [2]
We focus on identifying molecular prognostic markers that can predict the survival of stage IA lung adenocarcinoma patients, with the intention of finding reliable prognostic markers for better management and treatment of stage IA lung adenocarcinoma
Using tissue micro-dissection, we were able to capture at least 500 tumor cells from each patient specimen. 4 acinar subtype lung AC, which has a better prognosis, and 4 solid subtype lung AC, which has a worse prognosis, were selected for comparison of gene expression profiles using Affymetrix PrimView microarrays
Summary
Lung cancer is the leading cause of cancer related death worldwide [1] and adenocarcinoma (AC) is the most common histological type [2]. We and others have previously reported that the new International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society (IASLC/ ATS/ERS) lung AC classification [5] is significantly associated with patient survival, confirming the prognostic value of the new classification system [4, 6, 7]. Multiple studies involving gene expression profiling of lung cancers suggest that gene expression signatures in addition to the IASLC/ATS/ERS system can be used to improve the prediction of patient survival [8,9,10,11]. We focus on identifying molecular prognostic markers that can predict the survival of stage IA lung adenocarcinoma patients, with the intention of finding reliable prognostic markers for better management and treatment of stage IA lung adenocarcinoma
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