Zhu Xiao, Luo Hui, Xu Ying
1Southern Marine Science and Engineering Guangdong Laboratory-Zhanjiang, The Marine Biomedical Research Institute, Guangdong Medical University, Zhanjiang, China.
2Computational Systems Biology Lab (CSBL), Institute of Bioinformatics, University of Georgia, Athens, GA 30902 USA.
Cell Biosci. 2019 Nov 19;9:92. doi: 10.1186/s13578-019-0356-1. eCollection 2019.
Lymph node metastasis of lung cancer is a serious problem. Therefore, there is a need for a detailed transcriptome study of metastatic lung adenocarcinoma. The lung adenocarcinoma RNA-seq data and the corresponding clinical information available from TCGA were analyzed. Differential expression, gradient changes, and biological pathways were carried out. Potential gene(s) associated with tumor metastasis and survival were validated by Cox regression. A total of 406 and 439 differentially expressed genes were identified for lymph node metastasis and TNM stages, respectively. Of the 296 intersection genes, 112 were associated with nodal metastasis and/or staging. Only 25 of these 112 genes with gradient changes were involved in nodal metastasis, and 13 were involved in staging. Only one gene, RN7SL494P, might be involved in lung adenocarcinoma development and poor outcome. Finally, Cox regression results verified that age, pathology classification, radiotherapy and chemotherapy are all the independent prognostic factors. In particular, RN7SL494P was further verified to be an independent factor affecting lymph node metastasis and patient survival. Furthermore, we verified the RN7SL494P function using simulation data generated by mixing cell lines of the Cancer Cell Line Encyclopedia (CCLE) and obtained consistent results. Our findings suggest a potential clinical application of the RN7SL494P as a promising marker in the evaluation of patients with primary lung adenocarcinoma, not only for predicting nodal metastasis, but also for the prognosis of the outcome.
肺癌的淋巴结转移是一个严重的问题。因此，有必要对转移性肺腺癌进行详细的转录组研究。分析了来自TCGA的肺腺癌RNA测序数据及相应的临床信息。进行了差异表达、梯度变化及生物学通路分析。通过Cox回归验证了与肿瘤转移和生存相关的潜在基因。分别鉴定出406个和439个与淋巴结转移及TNM分期相关的差异表达基因。在296个交集基因中，112个与淋巴结转移和/或分期相关。这112个有梯度变化的基因中，仅25个参与淋巴结转移，13个参与分期。只有一个基因RN7SL494P可能参与肺腺癌的发生发展及不良预后。最后，Cox回归结果证实年龄、病理分类、放疗和化疗均为独立的预后因素。特别是，RN7SL494P被进一步证实是影响淋巴结转移和患者生存的独立因素。此外，我们使用癌细胞系百科全书（CCLE）的细胞系混合生成的模拟数据验证了RN7SL494P的功能，并获得了一致的结果。我们的研究结果表明，RN7SL494P在评估原发性肺腺癌患者中有潜在的临床应用价值，不仅可用于预测淋巴结转移，还可用于判断预后。
