Assessment of tumor-associated fibroblast as a biomarker for predicting recurrence of non-muscle invasive bladder cancer

Yin Hubin; Li Tinghao; Chen Junrui; Feng Zhenwei; Gou Xin; He Weiyang

doi:10.13406/j.cnki.cyxb.003292.

您当前的位置：

首页 >

文章列表页 >

Assessment of tumor-associated fibroblast as a biomarker for predicting recurrence of non-muscle invasive bladder cancer

Carcinoma of bladder | 更新时间：2025-10-21

- Assessment of tumor-associated fibroblast as a biomarker for predicting recurrence of non-muscle invasive bladder cancer
- Journal of Chongqing Medical University Vol. 48, Issue 8, Pages: 869-874(2023)
- 作者机构：
  
  重庆医科大学附属第一医院泌尿外科，重庆 400016
- 作者简介：
- 基金信息：
- DOI：10.13406/j.cnki.cyxb.003292.
  CLC： R737.14
- Received：04 June 2023，
  
  Revised：2023-06-25，
  
  Accepted：07 July 2023，
  
  Published：28 August 2023
- 稿件说明：
移动端阅览
印胡滨,李庭浩,陈俊睿,等.肿瘤相关成纤维细胞作为预测非肌层浸润性膀胱癌复发的生物标志物的评估[J].重庆医科大学学报,2023,48(8):869-874.

Yin Hubin,Li Tinghao,Chen Junrui,et al.Assessment of tumor-associated fibroblast as a biomarker for predicting recurrence of non-muscle invasive bladder cancer[J].Journal of Chongqing Medical University,2023,48(8):869-874.
印胡滨,李庭浩,陈俊睿,等.肿瘤相关成纤维细胞作为预测非肌层浸润性膀胱癌复发的生物标志物的评估[J].重庆医科大学学报,2023,48(8):869-874. DOI： 10.13406/j.cnki.cyxb.003292..

Yin Hubin,Li Tinghao,Chen Junrui,et al.Assessment of tumor-associated fibroblast as a biomarker for predicting recurrence of non-muscle invasive bladder cancer[J].Journal of Chongqing Medical University,2023,48(8):869-874. DOI： 10.13406/j.cnki.cyxb.003292..

摘要

目的

探究肿瘤相关成纤维细胞作为生物学标志物预测非肌层浸润性膀胱癌（non-muscle invasive bladder cancer，NMIBC）患者术后复发的临床意义。

方法

从基因表达综合（Gene Expression Omnibus，GEO）数据库下载转录组数据以及对应的临床信息，分析原发性和复发性膀胱癌样本中ACTA2的表达差异。免疫组织化学法（immunohistochemistry，IHC）检测56例膀胱癌样本中α-平滑肌肌动蛋白（α-smooth muscle actin，α-SMA）表达。绘制无复发生存曲线（recurrence-free survival，RFS）和时间依赖性受试者工作特征曲线（time-dependent receiver operating characteristic curves，tdROC）。采用单变量和多变量Cox比例风险回归模型分析α-SMA作为膀胱癌患者术后复发的预测因素的可行性。

结果

GSE13507、GSE120739和GSE128959数据集复发组中ACTA2的表达均高于原发组（

0.05）。IHC结果显示，α-SMA蛋白定位在肿瘤间质，复发组中α-SMA阳性/强阳性占比56.52%，而在原发组中占比16.13%，差异有统计学意义（

0.001）。α-SMA蛋白表达与年龄、性别、病理分期、分级、肿瘤数量和大小等指标无明显相关性。α-SMA高表达组患者术后RFS较低表达组患者明显缩短[风险比（hazard ratio，

）=2.76，95%可信区间（confidence interval，CI）=1.21~6.30，

=0.016

]

。多变量Cox分析显示，α-SMA蛋白表达水平是影响患者术后RFS的独立危险因素（

=2.47，95%CI=1.02~5.97，

=0.045）。tdROC曲线提示α-SMA对复发的预测能力优于其他临床因素。

结论

肿瘤间质的α-SMA蛋白表达水平与膀胱癌复发密切相关，可作为临床预测NMIBC患者术后复发的标志物。

Abstract

Objective

To investigate the clinical significance of tumor-associated fibroblast as a biomarker in predicting postoperative recurrence of non-muscle invasive bladder cancer（NMIBC）.

Methods

Transcriptomic data were downloaded from the Gene Expression Omnibus database along with corresponding clinical information to analyze the differences in ACTA2 expression in primary and recurrent bladder cancer samples. Immunohistochemistry（IHC） was used to determine α-smooth muscle actin（α-SMA） expression in 56 bladder cancer samples. Recurrence-free survival（RFS） curves and time-dependent receiver operating characteristic（tdROC） curves were plotted. Univariate and multivariate

Cox

proportional hazard regression models were used to analyze the feasibility of α-SMA as a predictor of postoperative recurrence of bladder cancer.

Results

The expression of ACTA2 was significantly higher in the recurrence group than in the primary group in the GSE13507，GSE120739，and GSE128959 datasets（

0.05）. IHC results showed that α-SMA protein was localized in the tumor stoma，and the percentage of positive/strongly positive α-SMA was 56.52% in the recurrence g

roup and 16.13% in the primary group，with a significant difference between the two groups（

0.001）. There was no significant correlation between α-SMA protein expression and age，gender，pathological stage，grade，tumor number，and size. Postoperative RFS was significantly shorter in patients with high α-SMA expression than in those with low α-SMA expression [hazard ratio（

）=2.76，95% confidence interval（CI）=1.21~6.30，

=0.016

]

. Multivariate

Cox

analysis showed that α-SMA protein expression level was an independent risk factor for postoperative RFS in patients（

=2.47，95%CI=1.02~5.97，

=0.045）. tdROC curves suggested that α-SMA was a better predictor of recurrence than other clinical factors.

Conclusion

α-SMA protein expression level in the tumor stroma is closely related to the recurrence of bladder cancer and can be used as a clinical marker to predict postoperative recurrence of NMIBC.

关键词

Keywords

references

Xia C ， Dong X ， Li H ， et al . Cancer statistics in China and United States，2022： profiles，trends，and determinants [J ] . Chin Med J（Engl）， 2022 ， 135 （ 5 ）： 584 - 590 .

Ieda T ， Muto S ， Shimizu F ， et al . Development and validation of a novel recurrence risk stratification for initial non-muscle invasive bladder cancer in Asia [J ] . EBioMedicine ， 2016 ， 12 ： 98 - 104 .

Chhabra Y ， Weeraratna AT . Fibroblasts in cancer： Unity in heterogeneity [J ] . Cell ， 2023 ， 186 （ 8 ）： 1580 - 1609 .

Rudnick JA ， Kuperwasser C . Stromal biomarkers in breast cancer development and progression [J ] . Clin Exp Metastasis ， 2012 ， 29 （ 7 ）： 663 - 72 .

Han C ， Liu T ， Yin R . Biomarkers for cancer-associated fibroblasts [J ] . Biomark Res ， 2020 ， 8 （ 1 ）： 64 .

Dourado MR ， Guerra E ， Salo T ， et al . Prognostic value of the immunohistochemical detection of cancer-associated fibroblasts in oral cancer：a systematic review and Meta-analysis [J ] . J Oral Pathol Med ， 2018 ， 47 （ 5 ）： 443 - 453 .

Lee JS ， Leem SH ， Lee SY ， et al . Expression signature of E2F1 and its associated genes predict superficial to invasive progression of bladder tumors [J ] . J Clin Oncol ， 2010 ， 28 （ 16 ）： 2660 - 2667 .

Sjödahl G ， Eriksson P ， Patschan O ， et al . Molecular changes during progression from nonmuscle invasive to advanced urothelial carcinoma [J ] . Int J Cancer ， 2020 ， 146 （ 9 ）： 2636 - 2647 .

Yin H ， He W ， Li Y ， et al . Loss of DUSP2 predicts a poor prognosis in patients with bladder cancer [J ] . Hum Pathol ， 2019 ， 85 ： 152 - 161 .

Daza J ， Grauer R ， Chen S ， et al . Development of a predictive model for recurrence-free survival in pTa low-grade bladder cancer [J ] . Urol Oncol ， 2023 ， 41 （ 5 ）： 256.e9 - 256.e15 .

Zhao L ， Sun J ， Wang K ， et al . Development of a new recurrence-free survival prediction nomogram for patients with primary non-muscle-invasive bladder cancer based on preoperative controlling nutritional status score [J ] . Cancer Manag Res ， 2021 ， 13 ： 6473 - 6487 .

Jobczyk M ， Stawiski K ， Fendler W ， et al . Validation of EORTC，CUETO，and EAU risk stratification in prediction of recurrence，progression，and death of patients with initially non-muscle-invasive bladder cancer（NMIBC）： a cohort analysis [J ] . Cancer Med ， 2020 ， 9 （ 11 ）： 4014 - 4025 .

汪玉倩，徐可，詹月萍，等 . 肿瘤相关成纤维细胞及其标记物的研究现状 [J ] . 中国临床药理学杂志， 2022 ， 38 （ 17 ）： 2094 - 2097 .

Wang YQ ， Xu K ， Zhan YP ， et al . Current status of research on tumor-associated fibroblasts and their markers [J ] . Chinese Journal of Clinical Pharmacology ， 2022 ， 38 （ 17 ）： 2094 - 2097 .

Eguchi S ， Yamada D ， Kobayashi S ， et al . Automated analysis for the prevalence of cancer-associated fibroblasts in resected specimens of intrahepatic cholangiocarcinoma is a simple and reliable evaluation system [J ] . Ann Surg Oncol ， 2023 ， 30 ： 5420 - 5428 .

Takagi K ， Noma K ， Nagai Y ， et al . Impact of cancer-associated fibroblasts on survival of patients with ampullary carcinoma [J ] . Front Oncol ， 2023 ， 13 ： 1072106 .

Kubouchi Y ， Yurugi Y ， Wakahara M ， et al . Podoplanin expression in cancer-associated fibroblasts predicts unfavourable prognosis in patients with pathological stage IA lung adenocarcinoma [J ] . Histopathology ， 2018 ， 72 （ 3 ）： 490 - 499 .

Muilwijk T ， Akand M ， Daelemans S ， et al . Stromal marker fibroblast activation protein drives outcome in T1 non-muscle invasive bladder cancer [J ] . PLoS One ， 2021 ， 16 （ 9 ）： e0257195 .

Hu J ， Zhou L ， Song Z ， et al . The identification of new biomarkers for bladder cancer： a study based on TCGA and GEO datasets [J ] . J Cell Physiol ， 2019 ， 234 （ 9 ）： 15607 - 15618 .

Li P ， Cao J ， Li J ， et al . Identification of prognostic biomarkers associated with stromal cell infiltration in muscle-invasive bladder cancer by bioinformatics analyses [J ] . Cancer Med ， 2020 ， 9 （ 19 ）： 7253 - 7267 .

Goulet CR ， Champagne A ， Bernard G ， et al . Cancer-associated fibroblasts induce epithelial-mesenchymal transition of bladder cancer cells through paracrine IL-6 signalling [J ] . BMC Cancer ， 2019 ， 19 （ 1 ）： 137 .

Zhuang J ， Shen L ， Li M ， et al . Cancer-associated fibroblast-derived miR-146a-5p generates a niche that promotes bladder cancer stemness and chemoresistance [J ] . Cancer Res ， 2023 ， 83 （ 10 ）： 1611 - 1627 .

Zhou Z ， Cui D ， Sun MH ， et al . CAFs-derived MFAP5 promotes bladder cancer malignant behavior through NOTCH2/HEY1 signaling [J ] . FASEB J ， 2020 ， 34 （ 6 ）： 7970 - 7988 .

Views

下载量

CSCD

Alert me when the article has been cited

提交

Tools

Publicity Resources

Risk factors for the recurrence of craniopharyngioma

Correlation between LAT1 expression level and risk of postoperative relapse in patients with non-muscle invasive bladder cancer

Retroperitoneal enterogenous cyst with glandular epithelial carcinogenesis：A case report

Experimental study of romidepsin in reducing liver cirrhosis

Two therapeutic schemes for Ⅱ degree intrauterine adhesion:a clinical control study

Related Author

Tian Lihua

Zhong Liyong

Chen Jiangchuan

Zhang Xuan

Luo Huaming

Zhang Jiamo

Chen Guangqiang

Guo Shengren

Related Institution

Department of Endocrinology，Beijing Tiantan Hospital，Capital Medical University

Department of Urology，Yongchuan Hospital Affiliated to Chongqing Medical University

Department of Imaging Diagnosis，The Second Affiliated Hospital of Suzhou University

Key Laboratory of Molecular Biology for Infectious Diseases Founded by Ministry of Education,Chongqing Medical University

Department of Liver,the Second Affiliated Hospital,Chongqing Medical University

⁰