Zhang Jie, Shao Jinchen, Zhu Lei, Zhao Ruiying, Xing Jie, Wang Jun, Guo Xiaohui, Tu Shichun, Han Baohui, Yu Keke
Shanghai Chest Hospital, Shanghai JiaoTong University, Department of Pathology, Shanghai, China.
Tumor Initiation & Maintenance Program, Sanford Burnham Prebys Medical Discovery Institute, La Jolla.
Oncotarget. 2017 Aug 24;8(43):74846-74855. doi: 10.18632/oncotarget.20420. eCollection 2017 Sep 26.
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.
我们之前表明，不同的病理亚型与IA期肺腺癌（AC）患者的不同预后价值相关。我们假设不同亚型的差异基因表达谱可能是IA期肺腺癌预后的重要因素。我们对从IA期肺腺癌腺泡和实体为主型亚型患者的肿瘤组织中显微切割得到的样本进行了基因芯片基因表达谱分析。这些患者于2012年在中国上海胸科医院接受了肺叶切除术和纵隔淋巴结清扫术。所有患者均未接受术前治疗。我们进行了基因集富集分析（GSEA）以寻找与肿瘤亚型相关的基因表达特征。所有患者的组织学亚型均根据2015年世界卫生组织肺腺癌分类进行分类。我们发现实体为主型亚型患者富含参与RNA聚合酶活性以及p53通路失活的基因。此外，我们确定了一系列可能作为IA期肺腺癌预后标志物的基因。在TCGA数据库中的验证表明这些基因与生存相关，这表明它们是IA期肺腺癌新的预后因素。总之，我们通过基因表达谱分析结合组织病理学亚型分类，发现了IA期肺腺癌新的预后因素。
