CYR61 as a potential biomarker for the preoperative identification of muscle-invasive bladder cancers

被引:8
|
作者
Chen, Huang [1 ,2 ]
Liu, Yu [1 ,2 ]
Cao, Chuanzhen [2 ,3 ]
Xi, Hao [1 ,2 ]
Chen, Wenting [1 ,2 ]
Zheng, Wei [2 ,3 ]
Dong, Xin [1 ,2 ]
Zheng, Shan [2 ,4 ]
Li, Lin [2 ,4 ]
Ma, Jianhui [2 ,3 ]
Gao, Yanning [1 ,2 ]
Shou, Jianzhong [2 ,3 ]
机构
[1] Chinese Acad Med Sci, Natl Canc Ctr, State Key Lab Mol Oncol, Canc Hosp, 17 Panjiayuan Nanli, Beijing 100021, Peoples R China
[2] Peking Union Med Coll, 17 Panjiayuan Nanli, Beijing 100021, Peoples R China
[3] Chinese Acad Med Sci, Natl Canc Ctr, Dept Urol, Canc Hosp, 17 Panjiayuan Nanli, Beijing 100021, Peoples R China
[4] Chinese Acad Med Sci, Canc Hosp, Dept Pathol, Natl Canc Ctr, Beijing, Peoples R China
关键词
Bladder cancer (BC); muscle-invasive bladder cancers (MIBCs); non-muscle-invasive bladder cancers (NMIBCs); cysteine-rich angiogenic inducer 61 (CYR61); biomarker; UROTHELIAL CARCINOMA; PROGRESSION; EXPRESSION; IMPACT; GENES;
D O I
10.21037/atm-19-4511
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Background: The biological behaviors, clinical treatment, prognosis of non-muscle-invasive bladder cancers (NMIBCs) and muscle-invasive bladder cancers (MIBCs) are distinct. Accurate staging is pivotal in optimal therapy planning for bladder cancers (BCs). However, it is insufficient for urologists in preoperative determining whether the tumor has invaded within the muscularis propria through cystoscope and imaging methods (CT or MRI). Therefore, searching for ideal biomarkers from the tumor tissues and urine is important for identifying the MIBCs preoperatively. Methods: Differentially expressed genes between NMIBCs and MIBCs were identified by microarray analysis and validated by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and immunohistochemical analysis. The correlation between cysteine-rich angiogenic inducer 61 (CYR61) expression and Kaplan-Meier test evaluated patients' overall survival (OS). CYR61 protein levels were measured using enzyme-linked immunosorbent assay (ELISA) in preoperatively collected urine samples from BC patients. The receiver-operating characteristic (ROC) curve analyzed the diagnostic accuracy of uric CYR61. The siRNA mediated silencing of CYR61 in bladder carcinoma cells was performed using Lipofectamine 2000. Cell migration and invasion were assessed using wound healing and transwell assay, respectively. Results: Differential gene expression analysis using microarray between 14 MIBCs and 16 NMIBCs human tumor samples revealed a significant increase (P<0.001) in the expression of CYR61 in MIBCs compared with NMIBCs. Higher expression of CYR61 in MIBCs was found in additional 54 tumor samples using qRT-PCR. Therefore, the overexpression of CYR61 in MIBCs could be used as a potential biomarker to distinguish between MIBCs and NMIBCs. ELISA detected elevated levels of CYR61 in the urine samples of MIBC patients (average 2.5-fold) compared with NMIBCs, with 72.7% sensitivity and 86.0% specificity to distinguish MIBCs from NMIBCs. Wound healing and transwell assays using CYR61-silenced carcinoma cells indicated the role of CYR61 in cell migration and invasion. Conclusions: CYR61 expression is higher in MIBCs compared with NMIBCs and can serve as a promising biomarker for the preoperative diagnosis of MIBCs with prognostic value; however, multicentric prospective validation is essential for the further evaluation of CYR61.
引用
收藏
页数:21
相关论文
共 50 条
  • [1] Aberrant expression of CYR61 in bladder cancer and its preoperative diagnostic potential in muscle invasive bladder cancer
    Chen, Huang
    Shou, Jianzhong
    Liu, Yu
    Zheng, Wei
    Xi, Hao
    Ma, Jianhui
    Gao, Yan Ning
    [J]. CANCER RESEARCH, 2015, 75
  • [2] CYR61 as a novel therapeutic target in muscle invasive bladder cancer
    Robinson, R. R.
    Brown, M.
    Ramani, V. A. C.
    Lau, M. W.
    Sangar, V. K.
    Clarke, N. W.
    [J]. BJU INTERNATIONAL, 2014, 113 : 22 - 23
  • [3] Serum Cyr61 as a potential biomarker for diagnosis of colorectal cancer
    Song, Y. F.
    Xu, Z. B.
    Zhu, X. J.
    Tao, X.
    Liu, J. L.
    Gao, F. L.
    Wu, C. L.
    Song, B.
    Lin, Q.
    [J]. CLINICAL & TRANSLATIONAL ONCOLOGY, 2017, 19 (04): : 519 - 524
  • [4] Serum Cyr61 as a potential biomarker for diagnosis of colorectal cancer
    Y. F. Song
    Z. B. Xu
    X. J. Zhu
    X. Tao
    J. L. Liu
    F. L. Gao
    C. L. Wu
    B. Song
    Q. Lin
    [J]. Clinical and Translational Oncology, 2017, 19 : 519 - 524
  • [5] Serum CYR61 as a potential biomarker to improve breast cancer diagnostics
    Lin, Zhen
    Song, Yanfang
    Qiu, Yaling
    Shi, Pengchong
    Zeng, Menglu
    Cao, Yingping
    Zhu, Xianjin
    [J]. BIOMARKERS IN MEDICINE, 2022, 16 (15) : 1121 - 1128
  • [6] Serum CYR61 as a potential biomarker for the diagnosis of esophagogastric junction tumor
    Chu, Ling-Yu
    Zhou, Jian-Yuan
    Zhao, Yi-Xuan
    Ou, Yan-Ting
    Yang, Tian
    Peng, Yu-Hui
    Fang, Wang-Kai
    Xu, Yi-Wei
    Xie, Jian-Jun
    [J]. BIOSCIENCE REPORTS, 2021, 41 (06)
  • [7] CYSTEINE RICH 61 (CYR61): A POTENTIAL BIOMARKER ASSOCIATED WITH DISEASE ACTIVITY IN RHEUMATOID ARTHRITIS
    Fan, Yong
    Yang, Xinlei
    Zhao, Juan
    Sun, Xiaoying
    Xie, Wenhui
    Huang, Yanrong
    Li Guangtao
    Hao, Yanjie
    Zhang, Zhuoli
    [J]. ANNALS OF THE RHEUMATIC DISEASES, 2019, 78 : 1578 - 1578
  • [8] Bladder Sparing Approaches for Muscle-Invasive Bladder Cancers
    El-Taji, Omar M. S.
    Alam, Sameer
    Hussain, Syed A.
    [J]. CURRENT TREATMENT OPTIONS IN ONCOLOGY, 2016, 17 (03)
  • [9] Bladder Sparing Approaches for Muscle-Invasive Bladder Cancers
    Omar M. S. El-Taji
    Sameer Alam
    Syed A. Hussain
    [J]. Current Treatment Options in Oncology, 2016, 17
  • [10] Identification of targeted therapy for an aggressive subgroup of muscle-invasive bladder cancers
    Lebret, Thierry
    Neuzillet, Yann
    Houede, Nadine
    Rebouissou, Sandra
    Bernard-Pierrot, Isabelle
    De Reynies, Aurelien
    Benhamou, Simone
    Allory, Yves
    Radvanyi, Francois
    [J]. MOLECULAR & CELLULAR ONCOLOGY, 2015, 2 (04)