Molecular profiling identifies prognostic markers of stage IA lung adenocarcinoma

// Jie Zhang 1 , Jinchen Shao 1 , Lei Zhu 1 , Ruiying Zhao 1 , Jie Xing 1 , Jun Wang 2 , Xiaohui Guo 3 , Shichun Tu 4 , Baohui Han 5 and Keke Yu 1, 6 1 Shanghai Chest Hospital, Shanghai JiaoTong University, Department of Pathology, Shanghai, China 2 Tumor Initiation & Maintenance Program, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA 3 Bioinformatics Core, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA 4 Allele Biotechnology & Pharmaceuticals, Inc., Nancy Ridge Drive, San Diego, CA, USA 5 Shanghai Chest Hospital, Shanghai JiaoTong University, Department of Pulmonary Medicine, Shanghai, China 6 Shanghai Chest Hospital, Shanghai JiaoTong University, Department of Biobank, Shanghai, China Correspondence to: Keke Yu, email: ykkxx@shchest.org Keywords: lung adenocarcinoma, gene expression profiling, differently expressed genes (DEGs), acinar, solid Received: March 29, 2017 Accepted: June 16, 2017 Published: August 24, 2017 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.