目的 分析丝氨酸转运蛋白SFXN1在非小细胞肺癌中的表达，阐明其与肺癌患者分期和预后之间的关系。方法 通过TCGA、Oncomine、HPA、UALCAN及Kaplan-Meier Plotter（KM）数据库中肺癌公共数据集，分析丝氨酸转运蛋白SFXN1的表达量与肺癌分期和预后的关系。运用基因富集分析（GSEA）方法，探索SFXN1调控肺癌发生发展的可能分子机制。 结果 TCGA数据集分析显示丝氨酸转运蛋白SFXN1在非小细胞肺癌组织中的表达水平显著高于正常组织；Oncomine基因芯片数据集分析结果表明，肺腺癌组织SFXN1表达量明显高于正常肺组织，表达倍数分别为2.664（P<0.001）、2.156（P<0.001）、1.708（P<0.001）、1.956（P<0.001）、1.563（P<0.001）及1.653（P<0.001）。SFXN1蛋白在肺腺癌和肺鳞癌组织中均有中度以上的表达，而正常肺组织几乎不表达。TCGA及UALCAN数据集分析结果显示：分期越晚的肺腺癌组织SFXN1基因表达量越高；KM分析表明其表达量与肺腺癌患者预后相关（中位生存期，低表达组 vs 高表达组： 59.27个月 vs 41.93个月，P=0.0019）。GSEA结果显示肺腺癌SFXN1高表达样本富集了E2F 转录因子、MYC信号通路、G2M检查点、MTORC1复合物、糖酵解、DNA损伤修复和乏氧相关的基因集。结论 SFXN1在非小细胞肺癌组织中表达上调，且其高表达与肺腺癌患者不良预后相关，或可成为非小细胞肺癌的潜在分子标志及治疗靶点。
Abstract
Objective To explore the expression of serine transporter SFXN1 and its relationship with stage and prognosis of non-small cell lung cancer. Methods Expression and prognostic implications of SFXN1 in lung cancer were analyzed by bioinformatics methods with databases including TCGA, Oncomine, HPA, UALCAN and Kaplan Meier plotter. Gene set enrichment analysis (GSEA) was used to explore the possible mechanism of SFXN1 regulating the oncogenesis, development and prognosis of lung cancer. Results Analysis with TCGA dataset showed that the expression level of SFXN1 in NSCLC was significantly higher than that in normal tissues. Statistics analysis of the gene sets in Oncomine showed that the expression of SFXN1 in lung adenocarcinoma was significantly higher than that in normal lung tissue, and the relative expression fold-change were 2.664 (P<0.001), 2.156 (P<0.001), 1.708 (P<0.001), 1.956 (P<0.001), 1.563 (P<0.001) and 1.653 (P<0.001), respectively. Compared with normal lung tissue, expression of SFXN1 protein in adenocarcinoma and squamous cell carcinoma was higher. The results of TCGA and UALCAN dataset showed that there was a positive relation between expression of SFXN1and clinical stage of lung adenocarcinoma；Kaplan Meier plotter analysis indicated that the expression of SFXN1 was negatively related to the prognosis of lung adenocarcinoma cases (median survival time, low expression group vs high expression group： 59.27 months vs 41.93months, P=0.0019). GSEA results suggested that the high expression samples of SFXN1 were enriched with E2F transcription factors, Myc signaling pathway, G2M checkpoint, mTORC1 complex, glycolysis, DNA damage repair and hypoxia related gene sets in lung adenocarcinoma. Conclusion SFXN1 is highly expressed in non-small cell lung cancer, and significantly related to the prognosis of lung adenocarcinoma patients. It may provide a new potential molecular marker and therapeutic target for the diagnosis and treatment of non-small cell lung cancer.
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基金
国家自然科学基金项目（81602164）
武汉大学中南医院科技创新培育基金资助项目（znpy2019079）
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