临床医学论著

EPCR-PAR1抗炎通路在肾透明细胞癌中的预后价值*

  • 常地超 ,
  • 刘轩绮 ,
  • 朱凌妍 ,
  • 白力
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  • 1.包头医学院第一附属医院风湿免疫科;内蒙古包头 014010;
    2.包头医学院第一附属医院中心实验室(内蒙古自体免疫学重点实验室)
白 力

收稿日期: 2024-02-10

  网络出版日期: 2025-02-24

基金资助

* 国家自然科学基金项目(82160309);内蒙古自然科学基金项目(2020LH08001);包头医学院秦文斌基金项目(BYJJ-QWB202006);包头医学院科研创新项目(No.bycx2020011)

Prognostic value of EPCR-PAR1 anti-inflammatory pathway in kidney renal clear-cell carcinoma

  • CHANG Dichao ,
  • LIU Xuanqi ,
  • ZHU Lingyan ,
  • BAI Li
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  • 1. Department of Rheumatology and Immunology, The First Affiliated Hospital of Baotou Medical College, Baotou 014010, China;
    2. The Central Laboratory of the First Affiliated Hospieal of Baotou Medical College (Inner Mongolia Key Laboratory of Autoimmunology)

Received date: 2024-02-10

  Online published: 2025-02-24

摘要

目的:分析EPCR-PAR1抗炎通路与肾透明细胞癌(renal clear cell carcinoma,KIRC)的关系,进行深入全面的生物学分析,探索KIRC的新治疗靶点。方法:系统分析来自肿瘤基因组图谱数据库(the cancer genome atlas,TCGA)的KIRC癌组织和正常组织样本中EPCR-PAR1通路8个抗炎基因的表达,采用LASSO回归、COX回归构建预后指数,分析EPCR-PAR1通路相关抗炎基因表达与KIRC患者预后的关联。结果:本研究构建了一个包含5个基因的风险评分模型(Risk score=0.100 82×F3+0.046 40×PROC-0.353 21×vWF+0.152 82×CAV1+0.180 69×GRK5),通过时间依赖性ROC曲线分析模型的预测能力,结合Risk score和临床因素构建的预后模型具有良好的预测性能。将相关临床病理特征和风险评分进行单变量和多变量Cox回归分析发现,风险评分(HR=3.2,95% CI=1.9-5.6,P<0.000 1)是肾透明细胞癌的独立危险因素。结论:EPCR-PAR1抗炎通路中这8个基因可作为KIRC预后的辅助标志物。

本文引用格式

常地超 , 刘轩绮 , 朱凌妍 , 白力 . EPCR-PAR1抗炎通路在肾透明细胞癌中的预后价值*[J]. 包头医学院学报, 2025 , 41(1) : 60 -67 . DOI: 10.16833/j.cnki.jbmc.2025.01.011

Abstract

Objective: In this study, we analyzed the relationship between the EPCR-PAR1 anti-inflammatory pathway and Kidney renal clear-cell carcinoma (KIRC), conducted an in-depth and comprehensive biological analysis, and explored new therapeutic targets in KIRC. Methods: We systematically analyzed expression of eight anti-inflammatory genes of the EPCR-PAR1 pathway in KIRC and normal samples from The Cancer Genome Atlas (TCGA) KIRC database. Using least absolute shrinkage and selection operator LASSO cox regression analysis to get a prognostic signature based on EPCR-PAR1 pathway expression. Results: We created a five-gene risk score model (risk score=0.100 82×F3+0.046 40×PROC-0.353 21×vWF+0.152 82×CAV1+0.180 69×GRK5). The prediction ability of the model was analyzed by the time-dependent ROC curve, and the prognosis model constructed by combining risk score and clinical factors had good prediction performance. Univariate and multivariate Cox regression analyses of relevant clinicopathological characters and risk score revealed that risk score was an independent risk factor for KIRC [hazard ratio (HR), 3.2; 95% confidence interval(CI), 1.9-5.6; P<0.000 1]. Conclusion: Genes in the EPCR-PAR1 anti-inflammatory pathway could serve as auxiliary markers in the diagnosis and prognosis of KIRC.

参考文献

[1] Ljungberg B, Bensalah K, Canfield S, et al. EAU guidelines on renal cell carcinoma: 2014 update[J]. Eur Urol, 2015, 67(5): 913-924.
[2] Torre LA, Bray F, Siegel RL, et al. Global cancer statistics, 2012[J]. CA Cancer J Clin, 2015, 65(2): 87-108.
[3] Cui H, Shan H, Miao MZ, et al. Identification of the key genes and pathways involved in the tumorigenesis and prognosis of kidney renal clear cell carcinoma[J]. Sci Rep, 2020, 10(1): 4271.
[4] Lohse CM, Cheville JC. A review of prognostic pathologic features and algorithms for patients treated surgically for renal cell carcinoma[J]. Clin Lab Med, 2005, 25(2): 433-464.
[5] Golshayan AR, George S, Heng DY, et al. Metastatic sarcomatoid renal cell carcinoma treated with vascular endothelial growth factor-targeted therapy[J]. J Clin Oncol, 2009, 27(2): 235-241.
[6] Schutz FA, Xie W, Donskov F, et al. The impact of low serum sodium on treatment outcome of targeted therapy in metastatic renal cell carcinoma: results from the International Metastatic Renal Cell Cancer Database Consortium[J]. Euro Urol, 2014, 65(4): 723-730.
[7] Mantovani A, Allavena P, Sica A, et al. Cancer-related inflammation[J]. Nature, 2008, 454(7203): 436-444.
[8] Bryant T. Remarks on some cases of inflammation of the breast simulating cancer[J]. Br Med J, 1868, 2(415): 608-609.
[9] Waldner MJ, Neurath MF. Colitis-associated cancer: the role of T cells in tumor development[J]. Sem Immunopathol, 2009, 31(2): 249-256.
[10] Murata M. Inflammation and cancer[J]. Environ Health Prev Med, 2018, 23(1): 50.
[11] Kondreddy V, Wang J, Keshava S, et al. Factor VIIa induces anti-inflammatory signaling via EPCR and PAR1[J]. Blood, 2018, 131(21): 2379-2392.
[12] Mitsui S, Oe Y, Sekimoto A, et al. Dual blockade of protease-activated receptor 1 and 2 additively ameliorates diabetic kidney disease[J]. Am J Physiol Renal Physiol, 2020, 318(5): F1067-1073.
[13] Mohan Rao LV, Esmon CT, Pendurthi UR. Endothelial cell protein C receptor: a multiliganded and multifunctional receptor[J]. Blood, 2014, 124(10): 1553-1562.
[14] Pendurthi UR, Rao LVM. Endothelial cell protein C receptor-dependent signaling[J]. Curr Opin Hematol, 2018, 25(3): 219-226.
[15] Pang L, Li JF, Su L, et al. ALEX1,a novel tumor suppressor gene,inhibits gastric cancer metastasis via the PAR-1/Rho GTPase signaling pathway[J]. J Gastroenterol, 2018, 53(1): 71-83.
[16] Han N, Li H, Wang H. MicroRNA-203 inhibits epithelial-mesenchymal transition, migration, and invasion of renal cell carcinoma cells via the inactivation of the PI3K/AKT signaling pathway by inhibiting CAV1[J]. Cell Adh Migr, 2020, 14(1): 227-241.
[17] Zhao TL, Gan XX, Bao Y, et al. GRK5 promotes tumor progression in renal cell carcinoma[J]. Neoplasma, 2019, 66(2): 261-70.
[18] Tang Z, Li C, Kang B, et al. GEPIA: a web server for cancer and normal gene expression profiling and interactive analyses[J]. Nucleic Acids Res, 2017, 45(W1): W98-102.
[19] Cao D, Qu Y, Zhang X, et al. High expression of F2RL3 correlates with aggressive features and poor survival in clear cell renal cell carcinoma[J]. J Cancer, 2018, 9(18): 3400-3406.
[20] Weinstein JN, Collisson EA, Mills GB, et al. The cancer genome atlas pan-cancer analysis project[J]. Nature Genetics, 2013, 45(10): 1113-1120.
[21] Goldman M, Craft B,Swatloski T,et al.The UCSC cancer genomics browser: update 2015[J]. Nucleic Acids Res, 2015, 43(Database issue): 812-817.
[22] Uhlén M, Fagerberg L,Hallström BM, et al. Proteomics tissue-based map of the human proteome[J]. Science (New York, NY), 2015, 347(6220): 1260419.
[23] Bazzi WM, Sjoberg DD, Feuerstein MA, et al. Long-term survival rates after resection for locally advanced kidney cancer: memorial sloan kettering cancer center 1989 to 2012 experience[J]. J Urol, 2015, 193(6): 1911-1916.
[24] Li P, Wong YN, Armstrong K, et al. Survival among patients with advanced renal cell carcinoma in the pretargeted versus targeted therapy eras[J]. Cancer Med, 2016, 5(2): 169-181.
[25] Amin MB, Greene FL, Edge SB, et al. The eighth edition AJCC cancer staging manual: continuing to build a bridge from a population-based to a more "personalized" approach to cancer staging[J]. CA Cancer J Clin 2017, 67(2): 93-99.
[26] Edge SB, Compton CC. The American joint committee on cancer: the 7th edition of the AJCC cancer staging manual and the future of TNM[J]. Ann Surg Oncol, 2010, 17(6): 1471-1474.
[27] Kim SP, Alt AL, Weight CJ, et al. Independent validation of the 2010 American Joint Committee on Cancer TNM classification for renal cell carcinoma: results from a large, single institution cohort[J]. J Urol, 2011, 185(6): 2035-2039.
[28] Ferlay J, Soerjomataram I, Dikshit R, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012[J]. Int J Cancer, 2015, 136(5): E359-386.
[29] Baco E, Rud E, Eri LM, et al. A randomized controlled trial to assess and compare the outcomes of two-core prostate biopsy guided by fused magnetic resonance and transrectal ultrasound images and traditional 12-core systematic biopsy[J]. Eur Urol, 2016, 69(1): 149-156.
[30] Szklarczyk D, Gable AL, Lyon D, et al. STRING v11: protein-protein association networks with increased coverage, supporting functional discovery in genome-wide experimental datasets[J]. Nucleic Acids Res, 2019, 47(D1): D607-613.
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