Upregulated Expression of CYBRD1 Predicts Poor Prognosis of Patients with Ovarian Cancer

被引:15
作者
Chen, Rui [1 ]
Cao, Jianhong [2 ]
Jiang, Wei [1 ]
Wang, Shunli [3 ]
Cheng, Jingxin [1 ]
机构
[1] Tongji Univ, Dept Gynecol, East Hosp, Shanghai 200012, Peoples R China
[2] Tongji Univ, Dept Heart Failure, East Hosp, Shanghai 200120, Peoples R China
[3] Tongji Univ, Dept Pathol, East Hosp, Shanghai 200120, Peoples R China
关键词
IRON; OVEREXPRESSION; METASTASIS; CELLS;
D O I
10.1155/2021/7548406
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Cytochrome b reductase 1 (CYBRD1) promotes the development of ovarian serous cystadenocarcinoma (OV). We assessed the function of CYBRD1 in OV underlying The Cancer Genome Atlas (TCGA) database. The correlation between clinicopathological characteristics and CYBRD1 expression was estimated. The Cox proportional hazards regression model and the Kaplan-Meier method were applied to identify clinical features related to overall survival and disease-specific survival. Gene set enrichment analysis (GSEA) was applied to identify the relationship between CYBRD1 expression and immune infiltration. CYBRD1 expression in OV was significantly associated with poor outcomes of primary therapy and FIGO stage. Patients with high levels of CYBRD1 expression were prone to the development of a poorly differentiated tumor and experience of an unfavorable outcome. CYBRD1 expression had significant association with shorter OS and acts as an independent predictor of poor outcome. Moreover, enhanced CYBRD1 expression was positively associated with Tem, NK cells, and mast cells but negatively associated with CD56 bright NK cells and Th2 cells. CYBRD1 expression may serve as a diagnostic and prognostic indicator of OV patients. The mechanisms of poor prognosis of CYBRD1-mediated OV may include increased iron uptake, regulation of immune microenvironment, ferroptosis related pathway, and ERK signaling pathway, among which ferroptosis and ERK signaling pathway may be important pathways of CYBRD1-mediated OV. Furthermore, we verified that CYBRD1 was upregulated in OV and significant correlated with lymph nodes metastasis, advanced stage, poor-differentiated tumor, and poor clinical prognosis in East Hospital cohort. The results of this study may provide guidance for the development of optimal treatment strategies for OV.
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页数:14
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共 40 条
[1]   Iron modulates cell survival in a Ras- and MAPK-dependent manner in ovarian cells [J].
Bauckman, K. A. ;
Haller, E. ;
Flores, I. ;
Nanjundan, M. .
CELL DEATH & DISEASE, 2013, 4 :e592-e592
[2]   Iron alters cell survival in a mitochondria-dependent pathway in ovarian cancer cells [J].
Bauckman, Kyle ;
Haller, Edward ;
Taran, Nicholas ;
Rockfield, Stephanie ;
Ruiz-Rivera, Abigail ;
Nanjundan, Meera .
BIOCHEMICAL JOURNAL, 2015, 466 :401-413
[3]   Spatiotemporal Dynamics of Intratumoral Immune Cells Reveal the Immune Landscape in Human Cancer [J].
Bindea, Gabriela ;
Mlecnik, Bernhard ;
Tosolini, Marie ;
Kirilovsky, Amos ;
Waldner, Maximilian ;
Obenauf, Anna C. ;
Angell, Helen ;
Fredriksen, Tessa ;
Lafontaine, Lucie ;
Berger, Anne ;
Bruneval, Patrick ;
Fridman, Wolf Herman ;
Becker, Christoph ;
Pages, Franck ;
Speicher, Michael R. ;
Trajanoski, Zlatko ;
Galon, Jerome .
IMMUNITY, 2013, 39 (04) :782-795
[4]   Overexpression of cellular iron import proteins is associated with malignant progression of Esophageal adenocarcinoma [J].
Boult, Jessica ;
Roberts, Keith ;
Brookes, Matthew J. ;
Hughes, Sharon ;
Bury, Jonathan P. ;
Cross, Simon S. ;
Anderson, Gregory J. ;
Spychal, Robert ;
Lqbal, Tariq ;
Tselepis, Chris .
CLINICAL CANCER RESEARCH, 2008, 14 (02) :379-387
[5]   A promising new approach to cancer therapy: Targeting iron metabolism in cancer stem cells [J].
El Hout, Mouradi ;
Dos Santos, Leila ;
Hamai, Ahmed ;
Mehrpour, Maryam .
SEMINARS IN CANCER BIOLOGY, 2018, 53 :125-138
[6]   Cancer statistics for the year 2020: An overview [J].
Ferlay, Jacques ;
Colombet, Murielle ;
Soerjomataram, Isabelle ;
Parkin, Donald M. ;
Pineros, Marion ;
Znaor, Ariana ;
Bray, Freddie .
INTERNATIONAL JOURNAL OF CANCER, 2021, 149 (04) :778-789
[7]   Cancer incidence and mortality worldwide: Sources, methods and major patterns in GLOBOCAN 2012 [J].
Ferlay, Jacques ;
Soerjomataram, Isabelle ;
Dikshit, Rajesh ;
Eser, Sultan ;
Mathers, Colin ;
Rebelo, Marise ;
Parkin, Donald Maxwell ;
Forman, David ;
Bray, Freddie .
INTERNATIONAL JOURNAL OF CANCER, 2015, 136 (05) :E359-E386
[8]   Dose-Response Association of CD8+ Tumor-Infiltrating Lymphocytes and Survival Time in High-Grade Serous Ovarian Cancer [J].
Goode, Ellen L. ;
Block, Matthew S. ;
Kalli, Kimberly R. ;
Vierkant, Robert A. ;
Chen, Wenqian ;
Fogarty, Zachary C. ;
Gentry-Maharaj, Aleksandra ;
Toloczko, Aleksandra ;
Hein, Alexander ;
Bouligny, Aliecia L. ;
Jensen, Allan ;
Osorio, Ana ;
Hartkopf, Andreas D. ;
Ryan, Andy ;
Chudecka-Glaz, Anita ;
Magliocco, Anthony M. ;
Hartmann, Arndt ;
Jung, Audrey Y. ;
Gao, Bo ;
Hernandez, Brenda Y. ;
Fridley, Brooke L. ;
McCauley, Bryan M. ;
Kennedy, Catherine J. ;
Wang, Chen ;
Karpinskyj, Chloe ;
de Sousa, Christiani B. ;
Tiezzi, Daniel G. ;
Wachter, David L. ;
Herpel, Esther ;
Taran, Florin Andrei ;
Modugno, Francesmary ;
Nelson, Gregg ;
Lubinski, Jan ;
Menkiszak, Janusz ;
Alsop, Jennifer ;
Lester, Jenny ;
Garcia-Donas, Jesus ;
Nation, Jill ;
Hung, Jillian ;
Palacios, Jose ;
Rothstein, Joseph H. ;
Kelley, Joseph L. ;
de Andrade, Jurandyr M. ;
Robles-Diaz, Luis ;
Intermaggio, Maria P. ;
Widschwendter, Martin ;
Beckmann, Matthias W. ;
Ruebner, Matthias ;
Jimenez-Linan, Mercedes ;
Singh, Naveena .
JAMA ONCOLOGY, 2017, 3 (12)
[9]   GSVA: gene set variation analysis for microarray and RNA-Seq data [J].
Haenzelmann, Sonja ;
Castelo, Robert ;
Guinney, Justin .
BMC BIOINFORMATICS, 2013, 14
[10]   Targeting Ferroptosis to Iron Out Cancer [J].
Hassannia, Behrouz ;
Vandenabeele, Peter ;
Vanden Berghe, Tom .
CANCER CELL, 2019, 35 (06) :830-849