丝氨酸转运蛋白SFXN1在非小细胞肺癌中的表达及临床意义

doi:10.16689/j.cnki.cn11-9349/r.2020.03.010

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摘要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。

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	江换钢
	罗园
	钟亚华
	周福祥
	谢丛华
	陈改丽

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.

基金资助: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）

通讯作者: 陈改丽，电子邮箱：gailichen@whu.edu.cn

引用本文:

江换钢，罗园，钟亚华，周福祥，谢丛华，陈改丽. 丝氨酸转运蛋白SFXN1在非小细胞肺癌中的表达及临床意义[J]. 肿瘤代谢与营养电子杂志, 2020, 7(3): 301-306.
Jiang Huangang, Luo Yuan, Zhong Yahua, Zhou Fuxiang, Xie Conghua, Chen Gaili. Expression and clinical significance of serine transporter SFXN1 in non-small cell lung cancer. Electron J Metab Nutr Cancer, 2020, 7(3): 301-306.

1.ARBOUR K C, RIELY G J. Systemic therapy for locally advanced and metastatic non-small cell lung cancer: a review［J］. JAMA, 2019, 322(8):764-774.
2.MARTINEZ P, PETERS S, STAMMERS T, et al. Immunotherapy for the first-line treatment of patients with metastatic non-small cell lung cancer［J］. Clin Cancer Res, 2019, 25(9):2691-2698.
3.BRAY F, FERLAY J, SOERJOMATARAM I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries［J］. CA Cancer J Clin, 2018, 68(6):394-424.
4.HIRSCH F R, SCAGLIOTTI G V, MULSHINE J L, et al. Lung cancer: current therapies and new targeted treatments［J］. Lancet, 2017, 389(10066):299-311.
5.DUCKER G S, RABINOWITZ J D. One-carbon metabolism in health and disease［J］. Cell Metab, 2017, 25(1):27-42.
6.LOCASALE J W. Serine, glycine and one-carbon units: cancer metabolism in full circle［J］. Nat Rev Cancer, 2013, 13(8):572-583.
7.YANG M, VOUSDEN K H. Serine and one-carbon metabolism in cance［J］. Nat Rev Cancer, 2016, 16(10):650-662.
8.NEWMAN A C, MADDOCKS O D K. One-carbon metabolism in cancer［J］. Br J Cancer, 2017, 116(12):1499-1504.
9.BURGOS-BARRAGAN G, WIT N, MEISER J, et al. Mammals divert endogenous genotoxic formaldehyde into one-carbon metabolism［J］. Nature, 2017, 548(7669):549-554.
10.FU T F, RIFE J P, SCHIRCH V. The role of serine hydroxymethyltransferase isozymes in one-carbon metabolism in MCF-7 cells as determined by (13)C NMR［J］. Arch Biochem Biophys, 2001, 393(1):42-50.
11.ZENG J D, WU W K K, WANG H Y, et al. Serine and one-carbon metabolism, a bridge that links mTOR signaling and DNA methylation in cancer［J］. Pharmacol Res, 2019, 149:104352.
12.BARLOWE C K, APPLING D R. In vitro evidence for the involvement of mitochondrial folate metabolism in the supply of cytoplasmic one-carbon units［J］. Biofactors, 1988, 1(2):171-176.
13.YU C, CLAYBROOK D L and HUANG A H. Transport of glycine, serine, and proline into spinach leaf mitochondria［J］. Arch Biochem Biophys, 1983, 227(1):180-187.
14.KORY N, WYANT G A, PRAKASH G, et al. SFXN1 is a mitochondrial serine transporter required for one-carbon metabolism［J］. Science, 2018, 362(6416):eaat9528.
15.TANG Z, LI C, B KANG, et al. GEPIA: a web server for cancer and normal gene expression profiling and interactive analyses［J］. Nucleic Acids Res, 2017, 45(W1):W98-W102.
16.CHANDRASHEKAR D S, BASHEL B, BALASUBRAMANYA S A H, et al. UALCAN: a portal for facilitating tumor subgroup gene expression and survival analyses［J］. Neoplasia, 2017, 19(8):649-658.
17.WANG W, ZHANG Y, LIU M, et al. TIMP2 is a poor prognostic factor and predicts metastatic biological behavior in gastric cancer［J］. Sci Rep, 2018, 8(1):9629.
18.POWERS R K, GOODSPEED A, PIELKE-LOMBARDO H, et al. GSEA-InContext: identifying novel and common patterns in expression experiments［J］. Bioinformatics, 2018, 34(13):i555-i564.
19.JU H Q, LU Y X, CHEN D L, et al. Modulation of redox homeostasis by inhibition of MTHFD2 in colorectal cancer: mechanisms and therapeutic implications［J］. J Natl Cancer Inst, 2019, 111(6):584-596.
20.NISHIMURA T, NAKATA A, CHEN X, et al. Cancer stem-like properties and gefitinib resistance are dependent on purine synthetic metabolism mediated by the mitochondrial enzyme MTHFD2［J］. Oncogene, 2019, 38(14):2464-2481.
21.LIU Y, YIN C, DENG M M, et al. High expression of SHMT2 is correlated with tumor progression and predicts poor prognosis in gastrointestinal tumors［J］. Eur Rev Med Pharmacol Sci, 2019, 23(21):9379-9392.
22.MIYAKE S, YAMASHITA T, TANIGUCHI M, et al. Identification and characterization of a novel mitochondrial tricarboxylate carrier［J］. Biochem Biophys Res Commun, 2002, 295(2):463-468.
23.LENOX L E, PERRY J M, PAULSON R F. BMP4 and Madh5 regulate the erythroid response to acute anemia［J］. Blood, 2005, 105(7):2741-2748.
24.FLEMING M D. Congenital sideroblastic anemias: iron and heme lost in mitochondrial translation［J］. Hematology Am Soc Hematol Educ Program, 2011, 2011:525-531.
25.TANG M, HUANG Z, LUO X, et al. Ferritinophagy activation and sideroflexin1-dependent mitochondria iron overload is involved in apelin-13-induced cardiomyocytes hypertrophy［J］. Free Radic Biol Med, 2019, 134:445-457.