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当代肿瘤药物靶点

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ISSN (Print): 1568-0096
ISSN (Online): 1873-5576

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Research Article

MTHFD家族在膀胱癌中的表达、预后价值及免疫浸润

卷 24, 期 2, 2024

发表于: 28 August, 2023

页: [178 - 191] 页: 14

弟呕挨: 10.2174/1568009623666230804152603

价格: $65

摘要

背景：亚甲基四氢叶酸脱氢酶(MTHFD)家族在多种肿瘤的发展和预后中起重要作用;然而，MTHFD家族在膀胱癌中的作用尚不清楚。 方法：利用R软件、cbiopportal、GeneMANIA和String-LinkedOmics等在线网站进行生物信息学分析。 结果：与正常组织相比，MTHFD1/1L/2在膀胱癌组织中表达显著上调，MTHFD家族高表达与较差的临床分级和分期密切相关，MTHFD1/1L/2表达上调的膀胱癌患者预后明显较差。基因功能和PPI网络分析显示MTHFD家族及其相关基因在膀胱癌的发生发展中发挥协同作用。利用800个与MTHFD家族相关的共表达基因进行功能富集分析，结果显示，许多基因与细胞周期、DNA复制等多种致癌途径相关。更重要的是，MTHFD家族与包括Treg细胞在内的多种浸润性免疫淋巴细胞以及TNFSF9、CD274、PDCD1等免疫分子密切相关。 结论：我们的研究表明MTHFD家族基因可能是膀胱癌患者潜在的预后标志物和治疗靶点。

关键词: 膀胱癌，预后标志物，MTHFD家族，免疫浸润，生物信息学分析，预后标志物。

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[1]
Siegel, R.L.; Miller, K.D.; Fuchs, H.E.; Jemal, A. Cancer statistics, 2021. CA Cancer J. Clin., 2021, 71(1), 7-33.
[http://dx.doi.org/10.3322/caac.21654] [PMID: 33433946]
[2]
Sung, H.; Ferlay, J.; Siegel, R.L.; Laversanne, M.; Soerjomataram, I.; Jemal, A.; Bray, F. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin., 2021, 71(3), 209-249.
[http://dx.doi.org/10.3322/caac.21660] [PMID: 33538338]
[3]
Grayson, M. Bladder cancer. Nature, 2017, 551(7679), S33.
[http://dx.doi.org/10.1038/551S33a] [PMID: 29117156]
[4]
Vasekar, M.; Degraff, D.; Joshi, M. Immunotherapy in bladder cancer. Curr. Mol. Pharmacol., 2016, 9(3), 242-251.
[http://dx.doi.org/10.2174/1874467208666150716120945] [PMID: 26177642]
[5]
Lenis, A.T.; Lec, P.M.; Chamie, K.; Mshs, M. Bladder Cancer. JAMA, 2020, 324(19), 1980-1991.
[http://dx.doi.org/10.1001/jama.2020.17598] [PMID: 33201207]
[6]
Ducker, G.S.; Rabinowitz, J.D. One-carbon metabolism in health and disease. Cell Metab., 2017, 25(1), 27-42.
[http://dx.doi.org/10.1016/j.cmet.2016.08.009] [PMID: 27641100]
[7]
Pietzke, M.; Meiser, J.; Vazquez, A. Formate metabolism in health and disease. Mol. Metab., 2020, 33, 23-37.
[http://dx.doi.org/10.1016/j.molmet.2019.05.012] [PMID: 31402327]
[8]
Li, A.M.; Ye, J. Reprogramming of serine, glycine and one-carbon metabolism in cancer. Biochim. Biophys. Acta Mol. Basis Dis., 2020, 1866(10), 165841.
[http://dx.doi.org/10.1016/j.bbadis.2020.165841] [PMID: 32439610]
[9]
Dekhne, A.S.; Hou, Z.; Gangjee, A.; Matherly, L.H. Therapeutic targeting of mitochondrial one-carbon metabolism in cancer. Mol. Cancer Ther., 2020, 19(11), 2245-2255.
[http://dx.doi.org/10.1158/1535-7163.MCT-20-0423] [PMID: 32879053]
[10]
Labuschagne, C.F.; van den Broek, N.J.F.; Mackay, G.M.; Vousden, K.H.; Maddocks, O.D.K. Serine, but not glycine, supports one-carbon metabolism and proliferation of cancer cells. Cell Rep., 2014, 7(4), 1248-1258.
[http://dx.doi.org/10.1016/j.celrep.2014.04.045] [PMID: 24813884]
[11]
He, D.; Yu, Z.; Liu, S.; Dai, H.; Xu, Q.; Li, F. Methylenetetrahydrofolate dehydrogenase 1 (MTHFD1) is underexpressed in clear cell renal cell carcinoma tissue and transfection and overexpression in caki-1 cells inhibits cell proliferation and increases apoptosis. Med. Sci. Monit., 2018, 24, 8391-8400.
[http://dx.doi.org/10.12659/MSM.911124] [PMID: 30459299]
[12]
Cui, L.; Zhao, X.; Jin, Z.; Wang, H.; Yang, S.F.; Hu, S. Melatonin modulates metabolic remodeling in HNSCC by suppressing MTHFD1L-formate axis. J. Pineal Res., 2021, 71(4), e12767.
[http://dx.doi.org/10.1111/jpi.12767] [PMID: 34533844]
[13]
Chen, J.; Yang, J.; Xu, Q.; Wang, Z.; Wu, J.; Pan, L.; Huang, K.; Wang, C. Integrated bioinformatics analysis identified MTHFD1L as a potential biomarker and correlated with immune infiltrates in hepatocellular carcinoma. Biosci. Rep., 2021, 41(2), BSR20202063.
[http://dx.doi.org/10.1042/BSR20202063] [PMID: 33605411]
[14]
Yang, Y.S.; Yuan, Y.; Hu, W.P.; Shang, Q.X.; Chen, L.Q. The role of mitochondrial folate enzyme MTHFD1L in esophageal squamous cell carcinoma. Scand. J. Gastroenterol., 2018, 53(5), 533-540.
[http://dx.doi.org/10.1080/00365521.2017.1407440] [PMID: 29171320]
[15]
Agarwal, S.; Behring, M.; Hale, K.; Al Diffalha, S.; Wang, K.; Manne, U.; Varambally, S. MTHFD1L, a folate cycle enzyme, is involved in progression of colorectal cancer. Transl. Oncol., 2019, 12(11), 1461-1467.
[http://dx.doi.org/10.1016/j.tranon.2019.07.011] [PMID: 31421459]
[16]
Shi, L.; Zhang, Q.; Shou, X.; Niu, H. Expression and prognostic value identification of methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) in brain low-grade glioma. Int. J. Gen. Med., 2021, 14, 4517-4527.
[http://dx.doi.org/10.2147/IJGM.S323858] [PMID: 34421310]
[17]
Huang, J.; Qin, Y.; Lin, C.; Huang, X.; Zhang, F. MTHFD2 facilitates breast cancer cell proliferation via the AKT signaling pathway. Exp. Ther. Med., 2021, 22(1), 703.
[http://dx.doi.org/10.3892/etm.2021.10135] [PMID: 34007312]
[18]
Shi, Y.; Xu, Y.; Yao, J.; Yan, C.; Su, H.; Zhang, X.; Chen, E.; Ying, K. MTHFD2 promotes tumorigenesis and metastasis in lung adenocarcinoma by regulating AKT/GSK-3β/β-catenin signalling. J. Cell. Mol. Med., 2021, 25(14), 7013-7027.
[http://dx.doi.org/10.1111/jcmm.16715] [PMID: 34121323]
[19]
Cerami, E.; Gao, J.; Dogrusoz, U.; Gross, B.E.; Sumer, S.O.; Aksoy, B.A.; Jacobsen, A.; Byrne, C.J.; Heuer, M.L.; Larsson, E.; Antipin, Y.; Reva, B.; Goldberg, A.P.; Sander, C.; Schultz, N. The cBio cancer genomics portal: An open platform for exploring multidimensional cancer genomics data. Cancer Discov., 2012, 2(5), 401-404.
[http://dx.doi.org/10.1158/2159-8290.CD-12-0095] [PMID: 22588877]
[20]
Warde-Farley, D. The GeneMANIA prediction server: Biological network integration for gene prioritization and predicting gene function. Nucleic Acids Res., 2010, 38(Web Server issue), W214-20.
[http://dx.doi.org/10.1093/nar/gkq537]
[21]
Szklarczyk, D.; Gable, A.L.; Nastou, K.C.; Lyon, D.; Kirsch, R.; Pyysalo, S.; Doncheva, N.T. The STRING database in 2021: Customizable protein-protein networks, and functional characterization of user-uploaded gene/measurement sets. Nucleic Acids Res., 2021, 49(D1), D605-D612.
[22]
Vasaikar, S.V.; Straub, P.; Wang, J.; Zhang, B. LinkedOmics: Analyzing multi-omics data within and across 32 cancer types. Nucleic Acids Res., 2018, 46(D1), D956-D963.
[http://dx.doi.org/10.1093/nar/gkx1090] [PMID: 29136207]
[23]
Ru, B.; Wong, C.N.; Tong, Y.; Zhong, J.Y.; Zhong, S.S.W.; Wu, W.C.; Chu, K.C.; Wong, C.Y.; Lau, C.Y.; Chen, I.; Chan, N.W.; Zhang, J. TISIDB: An integrated repository portal for tumor–immune system interactions. Bioinformatics, 2019, 35(20), 4200-4202.
[http://dx.doi.org/10.1093/bioinformatics/btz210] [PMID: 30903160]
[24]
Kan, J.; Moran, R.G. Intronic polyadenylation in the human glycinamide ribonucleotide formyltransferase gene. Nucleic Acids Res., 1997, 25(15), 3118-3123.
[http://dx.doi.org/10.1093/nar/25.15.3118] [PMID: 9224613]
[25]
Kawamura, T.; Takehora, Y.; Hori, N.; Takakura, Y.; Yamaguchi, N.; Takano, H.; Yamaguchi, N. VGLL3 increases the dependency of cancer cells on de novo nucleotide synthesis through GART expression. J. Cell. Biochem., 2022, 123(6), 1064-1076.
[http://dx.doi.org/10.1002/jcb.30251] [PMID: 35434822]
[26]
Skrajnowska, D.; Bobrowska-Korczak, B. Role of zinc in immune system and anti-cancer defense mechanisms. Nutrients, 2019, 11(10), 2273.
[http://dx.doi.org/10.3390/nu11102273] [PMID: 31546724]
[27]
Parkin, J.; Cohen, B. An overview of the immune system. Lancet, 2001, 357(9270), 1777-1789.
[http://dx.doi.org/10.1016/S0140-6736(00)04904-7] [PMID: 11403834]
[28]
Wang, W.; Gu, W.; Tang, H.; Mai, Z.; Xiao, H.; Zhao, J.; Han, J. The emerging role of MTHFD family genes in regulating the tumor immunity of oral squamous cell carcinoma. J. Oncol., 2022, 2022, 1-18.
[http://dx.doi.org/10.1155/2022/4867730] [PMID: 35693982]
[29]
Yu, H.; Wang, H.; Xu, H.R.; Zhang, Y.C.; Yu, X.B.; Wu, M.C.; Jin, G.Z.; Cong, W.M. Overexpression of MTHFD1 in hepatocellular carcinoma predicts poorer survival and recurrence. Future Oncol., 2019, 15(15), 1771-1780.
[http://dx.doi.org/10.2217/fon-2018-0606] [PMID: 30997850]
[30]
Li, H.; Fu, X.; Yao, F.; Tian, T.; Wang, C.; Yang, A. MTHFD1L-mediated redox homeostasis promotes tumor progression in tongue squamous cell carcinoma. Front. Oncol., 2019, 9, 1278.
[http://dx.doi.org/10.3389/fonc.2019.01278] [PMID: 31867267]
[31]
Li, G. p53 deficiency induces MTHFD2 transcription to promote cell proliferat ion and restrain DNA damage. Proc. Natl. Acad. Sci., 118(28), e2019822118.
[32]
Shang, M. The folate cycle enzyme MTHFD2 induces cancer immune evasion through PD-L1 up-regulation. Nat Commun., 2011, 12(1), 1940.
[33]
Nishimura, T.; Nakata, A.; Chen, X.; Nishi, K.; Meguro-Horike, M.; Sasaki, S.; Kita, K.; Horike, S.; Saitoh, K.; Kato, K.; Igarashi, K.; Murayama, T.; Kohno, S.; Takahashi, C.; Mukaida, N.; Yano, S.; Soga, T.; Tojo, A.; Gotoh, N. Cancer stem-like properties and gefitinib resistance are dependent on purine synthetic metabolism mediated by the mitochondrial enzyme MTHFD2. Oncogene, 2019, 38(14), 2464-2481.
[http://dx.doi.org/10.1038/s41388-018-0589-1] [PMID: 30532069]
[34]
Li, Q.; Yang, F.; Shi, X.; Bian, S.; Shen, F.; Wu, Y.; Zhu, C.; Fu, F.; Wang, J.; Zhou, J.; Chen, Y. MTHFD2 promotes ovarian cancer growth and metastasis via activation of the STAT3 signaling pathway. FEBS Open Bio, 2021, 11(10), 2845-2857.
[http://dx.doi.org/10.1002/2211-5463.13249] [PMID: 34231329]
[35]
Zeng, Y.; Zhang, J.; Xu, M.; Chen, F.; Zi, R.; Yue, J.; Zhang, Y.; Chen, N.; Chin, Y.E. Roles of Mitochondrial Serine Hydroxymethyltransferase 2 (SHMT2) in Human Carcinogenesis. J. Cancer, 2021, 12(19), 5888-5894.
[http://dx.doi.org/10.7150/jca.60170] [PMID: 34476002]
[36]
Zhang, P.; Yang, Q. Overexpression of SHMT2 predicts a poor prognosis and promotes tumor cell growth in bladder cancer. Front. Genet., 2021, 12, 682856.
[http://dx.doi.org/10.3389/fgene.2021.682856] [PMID: 34149818]
[37]
Hinshaw, D.C.; Shevde, L.A. The tumor microenvironment innately modulates cancer progression. Cancer Res., 2019, 79(18), 4557-4566.
[http://dx.doi.org/10.1158/0008-5472.CAN-18-3962] [PMID: 31350295]

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