基于代谢相关基因构建卵巢癌分子亚型与预后模型

马 子建1, 张 尚荣1, 管 波2
1、阜阳师范大学
2、阜阳市人民医院

摘要


目的：基于TCGA数据库中卵巢癌(ovarian cancer, OV)中代谢相关基因数据和患者的临床数据，构建卵巢癌分子亚型，并构建预后分子标签，探索代谢与卵巢癌之间的关系。方法：首先下载TCGA数据库中587例卵巢癌患者临床数据以及卵巢癌转录组数据，筛选出代谢相关基因(Metabolism related genes，MRGS)表达数据，单因素回归分析筛选出与预后相关的MRGS，然后基于MRGS构建卵巢癌分子亚型和预后分子模型。结果：根据生存数据进行单因素Cox分析得到54种与卵巢癌预后相关基因，LASSO回归分析从中筛选出7种与卵巢癌预后相关的MRGS，分别为ADH1B、ALOX12、CD38、DHRS9、PRIM2、PYGB、UGT2B4，根据Consensus Cluster聚类分析构建OV分子亚型，发现不同分子亚型预后和肿瘤微环境不同。联合7种MRGS构建预后分子标签：Risk score=0.194064313*EXPADH1B + 0.656842088*EXPALOX12 - 0.478099045* EXPCD38 + 0.343695715*EXPDHRS9 - 0.445279792*EXPPRIM2 + 0.240618352*EXPPYGB + 6.513499461*EXPUGT2B4 (EXP，基因表达水平)。分子标签值能很好预测卵巢癌预后。结论：基于代谢相关基因构建卵巢癌分子亚型和分子标签可以很好的判断卵巢癌预后。代谢相关基因在卵巢癌发生发展中可能发挥了重要作用。

关键词


卵巢癌；生物信息学；代谢；分子分型；预后模型

全文:

PDF


参考


[1]KOSSAI M,LEARY A,SCOAZEC J Y,et al.Ovarian Cancer: A Heterogeneous Disease[J].Pathobiology:journal of immunopathology,molecular and cellular biology,2018,85(1-2):41-49.

[2]REDONDO A,GUERRA E,MANSO L,et al.SEOM clinical guideline in ovarian cancer[J].Clinical&translational oncology,2021,23(5):961-968.

[3]BHATT P，VHORA I，PATIL S，et al．Role of antibodies in diagnosis and treatment of ovarian cancer: Basic approach and clinical status[J]. Journal of controlled release:official journal of the Controlled Release Society vol，2016,226:148-167.

[4]REN T,SUN T T,WANG S,et al.Clinical analysis of chemo-resistance risk factors in endometriosis associated ovarian cancer[J].Journal of ovarian research,2018,11(1):40.

[5]WANG T,TANG T,JIANG Y,et al.PRIM2 Promotes Cell Cycle and Tumor Progression in p53-Mutant Lung Cancer[J]. Cancers,2022,14(14),3370.

[6]BAENKE F,PECK B,MIESS H，et al.Hooked on fat:the role of lipid synthesis in cancer metabolism and tumour development[J].Disease models & mechanisms,2013,6(6):1353–1363.

[7]REINFELD B I，MADDEN M Z，WOLF M M，et al.Cell-programmed nutrient partitioning in the tumour microenvironment[J].Nature,2021,593(7858):282-288

[8]WU F,ZHAO Z, CHAI R C,et al.Prognostic power of a lipid metabolism gene panel for diffuse gliomas[J].Journal of cellular and molecular medicine,2019,23(11):7741-7748.

[9]ZHOU Z,HUANG R,CHAI R, et al.Identification of an energy metabolism-related signature associated with clinical prognosis in diffuse glioma[J].Aging (Albany NY) 2018,10(11):3185-3209.

[10]YOSHIHAR A K,SHAHMORADGOLI M,MARTINEZ E,et al.Inferring tumour purity and stromal and immune cell admixture from expression data[J]. Nature Commun,2013,4:2612.

[11]NEWMAN A M, LIU C L,GREEN M R,et al.Robust enumeration of cell subsets from tissue expression profiles[J]. Nature Methods,2015,12(5):453-457.

[12]GE T,GU X,JIA R,et al.Crosstalk between metabolic reprogramming and epigenetics in cancer:updates on mechanisms and therapeutic opportunities[J].Cancer communications(London, England), 2022,42(11):1049-1082.

[13]GHARPURE K M，LARA O D，WEN Y，et al.ADH1B promotes mesothelial clearance and ovarian cancer infiltration[J].Oncotarget,2018,9(38):25115-25126.

[14]SUN D, MCDONNELL M,CHEN X S, et al.Human 12(R)-lipoxygenase and the mouse ortholog.Molecular cloning,expression, and gene chromosomal assignment[J]. The Journal of biological chemistry,1998,273(50):33540-33547.

[15]CHENG Z,CHEN Y,HUANG H, et al.Identification and Validation of a Novel Prognostic Signature Based on Ferroptosis-Related Genes in Ovarian Cancer[J].Vaccines,2023,11(2):205.

[16]NIJHOF I S, GROEN R W, NOORT W A, et al. Preclinical Evidence for the Therapeutic Potential of CD38-Targeted Immuno-Chemotherapy in Multiple Myeloma Patients Refractory to Lenalidomide and Bortezomib [J].Clinical cancer research: an official journal of the American Association for Cancer Research, 2015,21(12):2802-2810.

[17]NAGY Á, LANCZKY A, MENYHART O, et al. Validation of miRNA prognostic power in hepatocellular carcinoma using expression data of independent datasets[J]. Scientific reports.2018,8(1):9227.

[18]WANG T, TANG T, JIANG Y, et al. PRIM2 promotes cell cycle and tumor progression in p53-mutant lung cancer[J]. Cancers,2022,14(14):3370.

[19]ZHOU Y, JIN Z, WANG C. Glycogen phosphorylase B promotes ovarian cancer progression via Wnt/β-catenin signaling and is regulated by miR-133a-3p[J].Biomed Pharmacother,2019,120:109449.

[20]CHE X, YU D, WU Z, et al. Polymorphisms in UGT2B4 and susceptibility to pancreatic cancer[J].International journal of clinical and experimental medicine,2015,8(2):2702-2710.


Refbacks

  • 当前没有refback。