Molecular profiling identifies prognostic markers of stage IA lung adenocarcinoma
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Jie Zhang1, Jinchen Shao1, Lei Zhu1, Ruiying Zhao1, Jie Xing1, Jun Wang2, Xiaohui Guo3, Shichun Tu4, Baohui Han5 and Keke Yu1,6
1Shanghai Chest Hospital, Shanghai JiaoTong University, Department of Pathology, Shanghai, China
2Tumor Initiation & Maintenance Program, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA
3Bioinformatics Core, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA
4Allele Biotechnology & Pharmaceuticals, Inc., Nancy Ridge Drive, San Diego, CA, USA
5Shanghai Chest Hospital, Shanghai JiaoTong University, Department of Pulmonary Medicine, Shanghai, China
6Shanghai Chest Hospital, Shanghai JiaoTong University, Department of Biobank, Shanghai, China
Keke Yu, email: [email protected]
Keywords: lung adenocarcinoma, gene expression profiling, differently expressed genes (DEGs), acinar, solid
Received: March 29, 2017 Accepted: June 16, 2017 Published: August 24, 2017
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.
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