A novel signature to predict the neoadjuvant chemotherapy response of bladder carcinoma: Results from a territory multicenter real-world study
Background: Although neoadjuvant chemotherapy (NAC) has become the standard treatment option for muscle invasive bladder carcinoma (MIBC), its application is still limited because of the lack of biomarkers for NAC prediction.Methods: We conducted a territory multicenter real-world study to summarize...
| Main Authors: | , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2022-11-01
|
| Series: | Frontiers in Genetics |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2022.1047481/full |
| _version_ | 1798046202168606720 |
|---|---|
| author | Huihuang Li Huihuang Li Jiao Hu Jiao Hu Xiongbing Zu Xiongbing Zu Minfeng Chen Minfeng Chen Jinbo Chen Jinbo Chen Yihua Zou Ruoping Deng Gang Qin Wenze Li Jiansheng Tang Dingshan Deng Dingshan Deng Jinhui Liu Jinhui Liu Chunliang Cheng Chunliang Cheng Yu Cui Yu Cui Zhenyu Ou Zhenyu Ou |
| author_facet | Huihuang Li Huihuang Li Jiao Hu Jiao Hu Xiongbing Zu Xiongbing Zu Minfeng Chen Minfeng Chen Jinbo Chen Jinbo Chen Yihua Zou Ruoping Deng Gang Qin Wenze Li Jiansheng Tang Dingshan Deng Dingshan Deng Jinhui Liu Jinhui Liu Chunliang Cheng Chunliang Cheng Yu Cui Yu Cui Zhenyu Ou Zhenyu Ou |
| author_sort | Huihuang Li |
| collection | DOAJ |
| description | Background: Although neoadjuvant chemotherapy (NAC) has become the standard treatment option for muscle invasive bladder carcinoma (MIBC), its application is still limited because of the lack of biomarkers for NAC prediction.Methods: We conducted a territory multicenter real-world study to summarize NAC practice in China and its associated clinicopathologic variables with NAC response. Then, we developed and validated a robust gene-based signature for accurate NAC prediction using weighted correlation network analysis (WGCNA), the least absolute shrinkage and selector operation (LASSO) algorithm, a multivariable binary logistic regression model, and immunohistochemistry (IHC).Results: In total, we collected 69 consecutive MIBC patients treated with NAC from four clinical centers. The application of NAC in the real world was relatively safe, with only two grade Ⅳ and seven grade Ⅲ AEs and no treatment-related deaths being reported. Among these patients, 16 patients gave up surgery after NAC, leaving 53 patients for further analysis. We divided them into pathological response and non-response groups and found that there were more patients with a higher grade and stage in the non-response group. Patients with a pathological response could benefit from a significant overall survival (OS) improvement. In addition, univariate and multivariate logistic analyses indicated that tumor grade and clinical T stage were both independent factors for predicting NAC response. Importantly, we developed and validated a five-gene-based risk score for extremely high predictive accuracy for NAC response.Conclusion: NAC was relatively safe and could significantly improve OS for MIBC patients in the real-world practice. Our five-gene-based risk score could guide personalized therapy and promote the application of NAC. |
| first_indexed | 2024-04-11T23:33:41Z |
| format | Article |
| id | doaj.art-9888ade8657946a1972046f0b9e754c6 |
| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-04-11T23:33:41Z |
| publishDate | 2022-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Genetics |
| spelling | doaj.art-9888ade8657946a1972046f0b9e754c62022-12-22T03:57:00ZengFrontiers Media S.A.Frontiers in Genetics1664-80212022-11-011310.3389/fgene.2022.10474811047481A novel signature to predict the neoadjuvant chemotherapy response of bladder carcinoma: Results from a territory multicenter real-world studyHuihuang Li0Huihuang Li1Jiao Hu2Jiao Hu3Xiongbing Zu4Xiongbing Zu5Minfeng Chen6Minfeng Chen7Jinbo Chen8Jinbo Chen9Yihua Zou10Ruoping Deng11Gang Qin12Wenze Li13Jiansheng Tang14Dingshan Deng15Dingshan Deng16Jinhui Liu17Jinhui Liu18Chunliang Cheng19Chunliang Cheng20Yu Cui21Yu Cui22Zhenyu Ou23Zhenyu Ou24Department of Urology, Xiangya Hospital, Central South University, Changsha, ChinaNational Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Urology, Xiangya Hospital, Central South University, Changsha, ChinaNational Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Urology, Xiangya Hospital, Central South University, Changsha, ChinaNational Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Urology, Xiangya Hospital, Central South University, Changsha, ChinaNational Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Urology, Xiangya Hospital, Central South University, Changsha, ChinaNational Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Urology, The First People’s Hospital of Chenzhou, Chenzhou, ChinaDepartment of Urology, The Central Hospital of Yongzhou, Yongzhou, ChinaDepartment of Urology, The Central Hospital of Yongzhou, Yongzhou, ChinaDepartment of Urology, The First People’s Hospital of Xiangtan City, Xiangtan, ChinaDepartment of Urology, Affiliated Hospital of Xiangnan University, Chenzhou, ChinaDepartment of Urology, Xiangya Hospital, Central South University, Changsha, ChinaNational Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Urology, Xiangya Hospital, Central South University, Changsha, ChinaNational Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Urology, Xiangya Hospital, Central South University, Changsha, ChinaNational Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Urology, Xiangya Hospital, Central South University, Changsha, ChinaNational Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Urology, Xiangya Hospital, Central South University, Changsha, ChinaNational Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, ChinaBackground: Although neoadjuvant chemotherapy (NAC) has become the standard treatment option for muscle invasive bladder carcinoma (MIBC), its application is still limited because of the lack of biomarkers for NAC prediction.Methods: We conducted a territory multicenter real-world study to summarize NAC practice in China and its associated clinicopathologic variables with NAC response. Then, we developed and validated a robust gene-based signature for accurate NAC prediction using weighted correlation network analysis (WGCNA), the least absolute shrinkage and selector operation (LASSO) algorithm, a multivariable binary logistic regression model, and immunohistochemistry (IHC).Results: In total, we collected 69 consecutive MIBC patients treated with NAC from four clinical centers. The application of NAC in the real world was relatively safe, with only two grade Ⅳ and seven grade Ⅲ AEs and no treatment-related deaths being reported. Among these patients, 16 patients gave up surgery after NAC, leaving 53 patients for further analysis. We divided them into pathological response and non-response groups and found that there were more patients with a higher grade and stage in the non-response group. Patients with a pathological response could benefit from a significant overall survival (OS) improvement. In addition, univariate and multivariate logistic analyses indicated that tumor grade and clinical T stage were both independent factors for predicting NAC response. Importantly, we developed and validated a five-gene-based risk score for extremely high predictive accuracy for NAC response.Conclusion: NAC was relatively safe and could significantly improve OS for MIBC patients in the real-world practice. Our five-gene-based risk score could guide personalized therapy and promote the application of NAC.https://www.frontiersin.org/articles/10.3389/fgene.2022.1047481/fullbladder carcinomaneoadjuvant chemotherapypathological responsepersonalized therapyrisk score |
| spellingShingle | Huihuang Li Huihuang Li Jiao Hu Jiao Hu Xiongbing Zu Xiongbing Zu Minfeng Chen Minfeng Chen Jinbo Chen Jinbo Chen Yihua Zou Ruoping Deng Gang Qin Wenze Li Jiansheng Tang Dingshan Deng Dingshan Deng Jinhui Liu Jinhui Liu Chunliang Cheng Chunliang Cheng Yu Cui Yu Cui Zhenyu Ou Zhenyu Ou A novel signature to predict the neoadjuvant chemotherapy response of bladder carcinoma: Results from a territory multicenter real-world study Frontiers in Genetics bladder carcinoma neoadjuvant chemotherapy pathological response personalized therapy risk score |
| title | A novel signature to predict the neoadjuvant chemotherapy response of bladder carcinoma: Results from a territory multicenter real-world study |
| title_full | A novel signature to predict the neoadjuvant chemotherapy response of bladder carcinoma: Results from a territory multicenter real-world study |
| title_fullStr | A novel signature to predict the neoadjuvant chemotherapy response of bladder carcinoma: Results from a territory multicenter real-world study |
| title_full_unstemmed | A novel signature to predict the neoadjuvant chemotherapy response of bladder carcinoma: Results from a territory multicenter real-world study |
| title_short | A novel signature to predict the neoadjuvant chemotherapy response of bladder carcinoma: Results from a territory multicenter real-world study |
| title_sort | novel signature to predict the neoadjuvant chemotherapy response of bladder carcinoma results from a territory multicenter real world study |
| topic | bladder carcinoma neoadjuvant chemotherapy pathological response personalized therapy risk score |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2022.1047481/full |
| work_keys_str_mv | AT huihuangli anovelsignaturetopredicttheneoadjuvantchemotherapyresponseofbladdercarcinomaresultsfromaterritorymulticenterrealworldstudy AT huihuangli anovelsignaturetopredicttheneoadjuvantchemotherapyresponseofbladdercarcinomaresultsfromaterritorymulticenterrealworldstudy AT jiaohu anovelsignaturetopredicttheneoadjuvantchemotherapyresponseofbladdercarcinomaresultsfromaterritorymulticenterrealworldstudy AT jiaohu anovelsignaturetopredicttheneoadjuvantchemotherapyresponseofbladdercarcinomaresultsfromaterritorymulticenterrealworldstudy AT xiongbingzu anovelsignaturetopredicttheneoadjuvantchemotherapyresponseofbladdercarcinomaresultsfromaterritorymulticenterrealworldstudy AT xiongbingzu anovelsignaturetopredicttheneoadjuvantchemotherapyresponseofbladdercarcinomaresultsfromaterritorymulticenterrealworldstudy AT minfengchen anovelsignaturetopredicttheneoadjuvantchemotherapyresponseofbladdercarcinomaresultsfromaterritorymulticenterrealworldstudy AT minfengchen anovelsignaturetopredicttheneoadjuvantchemotherapyresponseofbladdercarcinomaresultsfromaterritorymulticenterrealworldstudy AT jinbochen anovelsignaturetopredicttheneoadjuvantchemotherapyresponseofbladdercarcinomaresultsfromaterritorymulticenterrealworldstudy AT jinbochen anovelsignaturetopredicttheneoadjuvantchemotherapyresponseofbladdercarcinomaresultsfromaterritorymulticenterrealworldstudy AT yihuazou anovelsignaturetopredicttheneoadjuvantchemotherapyresponseofbladdercarcinomaresultsfromaterritorymulticenterrealworldstudy AT ruopingdeng anovelsignaturetopredicttheneoadjuvantchemotherapyresponseofbladdercarcinomaresultsfromaterritorymulticenterrealworldstudy AT gangqin anovelsignaturetopredicttheneoadjuvantchemotherapyresponseofbladdercarcinomaresultsfromaterritorymulticenterrealworldstudy AT wenzeli anovelsignaturetopredicttheneoadjuvantchemotherapyresponseofbladdercarcinomaresultsfromaterritorymulticenterrealworldstudy AT jianshengtang anovelsignaturetopredicttheneoadjuvantchemotherapyresponseofbladdercarcinomaresultsfromaterritorymulticenterrealworldstudy AT dingshandeng anovelsignaturetopredicttheneoadjuvantchemotherapyresponseofbladdercarcinomaresultsfromaterritorymulticenterrealworldstudy AT dingshandeng anovelsignaturetopredicttheneoadjuvantchemotherapyresponseofbladdercarcinomaresultsfromaterritorymulticenterrealworldstudy AT jinhuiliu anovelsignaturetopredicttheneoadjuvantchemotherapyresponseofbladdercarcinomaresultsfromaterritorymulticenterrealworldstudy AT jinhuiliu anovelsignaturetopredicttheneoadjuvantchemotherapyresponseofbladdercarcinomaresultsfromaterritorymulticenterrealworldstudy AT chunliangcheng anovelsignaturetopredicttheneoadjuvantchemotherapyresponseofbladdercarcinomaresultsfromaterritorymulticenterrealworldstudy AT chunliangcheng anovelsignaturetopredicttheneoadjuvantchemotherapyresponseofbladdercarcinomaresultsfromaterritorymulticenterrealworldstudy AT yucui anovelsignaturetopredicttheneoadjuvantchemotherapyresponseofbladdercarcinomaresultsfromaterritorymulticenterrealworldstudy AT yucui anovelsignaturetopredicttheneoadjuvantchemotherapyresponseofbladdercarcinomaresultsfromaterritorymulticenterrealworldstudy AT zhenyuou anovelsignaturetopredicttheneoadjuvantchemotherapyresponseofbladdercarcinomaresultsfromaterritorymulticenterrealworldstudy AT zhenyuou anovelsignaturetopredicttheneoadjuvantchemotherapyresponseofbladdercarcinomaresultsfromaterritorymulticenterrealworldstudy AT huihuangli novelsignaturetopredicttheneoadjuvantchemotherapyresponseofbladdercarcinomaresultsfromaterritorymulticenterrealworldstudy AT huihuangli novelsignaturetopredicttheneoadjuvantchemotherapyresponseofbladdercarcinomaresultsfromaterritorymulticenterrealworldstudy AT jiaohu novelsignaturetopredicttheneoadjuvantchemotherapyresponseofbladdercarcinomaresultsfromaterritorymulticenterrealworldstudy AT jiaohu novelsignaturetopredicttheneoadjuvantchemotherapyresponseofbladdercarcinomaresultsfromaterritorymulticenterrealworldstudy AT xiongbingzu novelsignaturetopredicttheneoadjuvantchemotherapyresponseofbladdercarcinomaresultsfromaterritorymulticenterrealworldstudy AT xiongbingzu novelsignaturetopredicttheneoadjuvantchemotherapyresponseofbladdercarcinomaresultsfromaterritorymulticenterrealworldstudy AT minfengchen novelsignaturetopredicttheneoadjuvantchemotherapyresponseofbladdercarcinomaresultsfromaterritorymulticenterrealworldstudy AT minfengchen novelsignaturetopredicttheneoadjuvantchemotherapyresponseofbladdercarcinomaresultsfromaterritorymulticenterrealworldstudy AT jinbochen novelsignaturetopredicttheneoadjuvantchemotherapyresponseofbladdercarcinomaresultsfromaterritorymulticenterrealworldstudy AT jinbochen novelsignaturetopredicttheneoadjuvantchemotherapyresponseofbladdercarcinomaresultsfromaterritorymulticenterrealworldstudy AT yihuazou novelsignaturetopredicttheneoadjuvantchemotherapyresponseofbladdercarcinomaresultsfromaterritorymulticenterrealworldstudy AT ruopingdeng novelsignaturetopredicttheneoadjuvantchemotherapyresponseofbladdercarcinomaresultsfromaterritorymulticenterrealworldstudy AT gangqin novelsignaturetopredicttheneoadjuvantchemotherapyresponseofbladdercarcinomaresultsfromaterritorymulticenterrealworldstudy AT wenzeli novelsignaturetopredicttheneoadjuvantchemotherapyresponseofbladdercarcinomaresultsfromaterritorymulticenterrealworldstudy AT jianshengtang novelsignaturetopredicttheneoadjuvantchemotherapyresponseofbladdercarcinomaresultsfromaterritorymulticenterrealworldstudy AT dingshandeng novelsignaturetopredicttheneoadjuvantchemotherapyresponseofbladdercarcinomaresultsfromaterritorymulticenterrealworldstudy AT dingshandeng novelsignaturetopredicttheneoadjuvantchemotherapyresponseofbladdercarcinomaresultsfromaterritorymulticenterrealworldstudy AT jinhuiliu novelsignaturetopredicttheneoadjuvantchemotherapyresponseofbladdercarcinomaresultsfromaterritorymulticenterrealworldstudy AT jinhuiliu novelsignaturetopredicttheneoadjuvantchemotherapyresponseofbladdercarcinomaresultsfromaterritorymulticenterrealworldstudy AT chunliangcheng novelsignaturetopredicttheneoadjuvantchemotherapyresponseofbladdercarcinomaresultsfromaterritorymulticenterrealworldstudy AT chunliangcheng novelsignaturetopredicttheneoadjuvantchemotherapyresponseofbladdercarcinomaresultsfromaterritorymulticenterrealworldstudy AT yucui novelsignaturetopredicttheneoadjuvantchemotherapyresponseofbladdercarcinomaresultsfromaterritorymulticenterrealworldstudy AT yucui novelsignaturetopredicttheneoadjuvantchemotherapyresponseofbladdercarcinomaresultsfromaterritorymulticenterrealworldstudy AT zhenyuou novelsignaturetopredicttheneoadjuvantchemotherapyresponseofbladdercarcinomaresultsfromaterritorymulticenterrealworldstudy AT zhenyuou novelsignaturetopredicttheneoadjuvantchemotherapyresponseofbladdercarcinomaresultsfromaterritorymulticenterrealworldstudy |