High expression of interleukin-11 is an independent indicator of poor prognosis in clear-cell renal cell carcinoma

被引:28
作者
Pan, Deng [1 ]
Xu, Le [2 ]
Liu, Haiou [3 ]
Zhang, Weijuan [4 ]
Liu, Weisi [1 ]
Liu, Yidong [1 ]
Fu, Qiang [1 ]
Xu, Jiejie [1 ]
机构
[1] Fudan Univ, Sch Basic Med Sci, Dept Biochem & Mol Biol, Shanghai 54237332, Peoples R China
[2] Fudan Univ, Zhongshan Hosp, Dept Urol, Shanghai 54237332, Peoples R China
[3] Fudan Univ, Shanghai Key Lab Female Reprod Endocrine Related, Obstet & Gynecol Hosp, Shanghai 54237332, Peoples R China
[4] Fudan Univ, Sch Basic Med Sci, Dept Immunol, Shanghai 54237332, Peoples R China
基金
中国国家自然科学基金;
关键词
Clear-cell renal cell carcinoma; interleukin-11; overall survival; prognostic biomarker; recurrence-free survival; RETROSPECTIVE ANALYSIS; FAMILY CYTOKINE; CANCER; INFLAMMATION; IL-11; TUMORIGENESIS; RECEPTOR; STAT3;
D O I
10.1111/cas.12638
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Interleukin-11 (IL-11), a member of the IL-6 family of cytokines, exerts pleiotropic oncogenic activities by stimulating angiogenesis and metastasis in many cancer types. The present study aims to evaluate the impact of IL-11 expression on recurrence and mortality of patients with clear-cell renal cell carcinoma (ccRCC). We retrospectively enrolled 193 ccRCC patients undergoing nephrectomy at a single center. Clinicopathologic features, recurrence-free survival (RFS) and overall survival (OS) were recorded. IL-11 intensity was assessed by immunohistochemistry in tumor specimens. The Kaplan-Meier method was applied to compare survival curves. Cox regression models were used to analyze the impact of prognostic factors on RFS and OS. The concordance index (C-index) was calculated to assess predictive accuracy. High IL-11 expression is associated with increased risk of recurrence and poor survival for ccRCC patients (P<0.001 and P<0.001, respectively), especially those with early-stage disease (TNM stage I+II). Multivariate analyses confirmed that IL-11 expression was an independent prognostic factor for RFS and OS (P=0.006 and P=0.008, respectively). The predictive accuracy of well-established prognostic models was improved when IL-11 expression was integrated. In conclusion, high IL-11 expression is an independent predictor of poor prognosis in ccRCC patients. It may help identify patients who could benefit from additional treatments and closer follow up.
引用
收藏
页码:592 / 597
页数:6
相关论文
共 28 条
[1]   X-tile: A new bio-informatics tool for biomarker assessment and outcome-based cut-point optimization [J].
Camp, RL ;
Dolled-Filhart, M ;
Rimm, DL .
CLINICAL CANCER RESEARCH, 2004, 10 (21) :7252-7259
[2]   Comparisons of outcome and prognostic features among histologic subtypes of renal cell carcinoma [J].
Cheville, JC ;
Lohse, CM ;
Zincke, H ;
Weaver, AL ;
Blute, ML .
AMERICAN JOURNAL OF SURGICAL PATHOLOGY, 2003, 27 (05) :612-624
[3]   Interleukin-6 as a Therapeutic Target in Human Ovarian Cancer [J].
Coward, Jermaine ;
Kulbe, Hagen ;
Chakravarty, Probir ;
Leader, David ;
Vassileva, Vessela ;
Leinster, D. Andrew ;
Thompson, Richard ;
Schioppa, Tiziana ;
Nemeth, Jeffery ;
Vermeulen, Jessica ;
Singh, Naveena ;
Avril, Norbert ;
Cummings, Jeff ;
Rexhepaj, Elton ;
Jirstrom, Karin ;
Gallagher, William M. ;
Brennan, Donal J. ;
McNeish, Iain A. ;
Balkwill, Frances R. .
CLINICAL CANCER RESEARCH, 2011, 17 (18) :6083-6096
[4]   STAT3 and STAT1 mediate IL-11-dependent and inflammation-associated gastric tumorigenesis in gp130 receptor mutant mice [J].
Ernst, Matthias ;
Najdovska, Meri ;
Grail, Dianne ;
Lundgren-May, Therese ;
Buchert, Michael ;
Tye, Hazel ;
Matthews, Vance B. ;
Armes, Jane ;
Bhathal, Prithi S. ;
Hughes, Norman R. ;
Marcusson, Eric G. ;
Karras, James G. ;
Na, Songqing ;
Sedgwick, Jonathon D. ;
Hertzog, Paul J. ;
Jenkins, Brendan J. .
JOURNAL OF CLINICAL INVESTIGATION, 2008, 118 (05) :1727-1738
[5]   Molecular Pathways: IL11 as a Tumor-Promoting Cytokine-Translational Implications for Cancers [J].
Ernst, Matthias ;
Putoczki, Tracy L. .
CLINICAL CANCER RESEARCH, 2014, 20 (22) :5579-5588
[6]   Targeting IL-11 signaling in colon cancer [J].
Ernst, Matthias ;
Putoczki, Tracy L. .
ONCOTARGET, 2013, 4 (11) :1860-1861
[7]   An outcome prediction model for patients with clear cell renal cell carcinoma treated with radical nephrectomy based on tumor stage, size, grade and necrosis: The SSIGN score [J].
Frank, I ;
Blute, ML ;
Cheville, JC ;
Lohse, CM ;
Weaver, AL ;
Zincke, H .
JOURNAL OF UROLOGY, 2002, 168 (06) :2395-2400
[8]   Cytokines as a key component of cancer-related inflammation [J].
Germano, Giovanni ;
Allavena, Paola ;
Mantovani, Alberto .
CYTOKINE, 2008, 43 (03) :374-379
[9]   Immunity, Inflammation, and Cancer [J].
Grivennikov, Sergei I. ;
Greten, Florian R. ;
Karin, Michael .
CELL, 2010, 140 (06) :883-899
[10]   Interleukin-6 signaling pathway in targeted therapy for cancer [J].
Guo, Yuqi ;
Xu, Feng ;
Lu, Tianjian ;
Duan, Zhenfeng ;
Zhang, Zhan .
CANCER TREATMENT REVIEWS, 2012, 38 (07) :904-910