Clinical Application of Circulating Tumor Cells and Circulating Endothelial Cells in Predicting Bladder Cancer Prognosis and Neoadjuvant Chemosensitivity

To investigate the role of circulating rare cells (CRCs), namely, circulating tumor cells (CTCs) and circulating endothelial cells (CECs), in aiding early intervention, treatment decision, and prognostication in bladder cancer. A total of 196 patients with pathologically confirmed bladder cancer, na...

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Published inFrontiers in oncology Vol. 11; p. 802188
Main Authors Yang, Xiao, Lv, Jiancheng, Zhou, Zijian, Feng, Dexiang, Zhou, Rui, Yuan, Baorui, Wu, Qikai, Yu, Hao, Han, Jie, Cao, Qiang, Gu, Min, Li, Pengchao, Yang, Haiwei, Lu, Qiang
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LanguageEnglish
Published Switzerland Frontiers Media S.A 03.02.2022
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ISSN2234-943X
2234-943X
DOI10.3389/fonc.2021.802188

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Abstract To investigate the role of circulating rare cells (CRCs), namely, circulating tumor cells (CTCs) and circulating endothelial cells (CECs), in aiding early intervention, treatment decision, and prognostication in bladder cancer. A total of 196 patients with pathologically confirmed bladder cancer, namely, 141 non-muscle invasive bladder cancer (NMIBC) and 55 muscle invasive bladder cancer (MIBC) patients. There were 32 patients who received cisplatin-based neoadjuvant chemotherapy (NAC) followed by radical cystectomy (RC). Subtraction enrichment combined with immunostaining-fluorescence hybridization (SE-iFISH) strategy was used for CTC/CEC detection. Kaplan-Meier analysis and Cox regression were used to evaluate the overall survival (OS) and recurrence-free survival (RFS). Receiver operator characteristic analysis was used to discriminate NAC sensitivity. CTCs and CECs were related to clinicopathological characteristics. Triploid CTCs, tetraploid CTCs, and total CECs were found to be higher in incipient patients than in relapse patients ( = 0.036, = 0.019, and = 0.025, respectively). The number of total CECs and large cell CECs was also associated with advanced tumor stage ( = 0.028 and = 0.033) and grade ( = 0.028 and = 0.041). Remarkably, tumor-biomarker-positive CTCs were associated with worse OS and RFS ( = 0.026 and = 0.038) in NMIBC patients underwent TURBT. CECs cluster was an independent predictor of recurrence in non-high-risk NMIBC patients underwent TURBT (HR = 9.21, = 0.040). For NAC analysis, pre-NAC tetraploid CTCs and small cell CTCs demonstrated the capability in discriminating NAC-sensitive from insensitive patients. Additionally, tetraploid CTCs and single CTCs elevated post-NAC would indicate chemoresistance. CTCs and CECs may putatively guide in diagnosis, prognosis prediction, and therapeutic decision-making for bladder cancer.
AbstractList To investigate the role of circulating rare cells (CRCs), namely, circulating tumor cells (CTCs) and circulating endothelial cells (CECs), in aiding early intervention, treatment decision, and prognostication in bladder cancer.PURPOSETo investigate the role of circulating rare cells (CRCs), namely, circulating tumor cells (CTCs) and circulating endothelial cells (CECs), in aiding early intervention, treatment decision, and prognostication in bladder cancer.A total of 196 patients with pathologically confirmed bladder cancer, namely, 141 non-muscle invasive bladder cancer (NMIBC) and 55 muscle invasive bladder cancer (MIBC) patients. There were 32 patients who received cisplatin-based neoadjuvant chemotherapy (NAC) followed by radical cystectomy (RC). Subtraction enrichment combined with immunostaining-fluorescence in situ hybridization (SE-iFISH) strategy was used for CTC/CEC detection. Kaplan-Meier analysis and Cox regression were used to evaluate the overall survival (OS) and recurrence-free survival (RFS). Receiver operator characteristic analysis was used to discriminate NAC sensitivity.METHODSA total of 196 patients with pathologically confirmed bladder cancer, namely, 141 non-muscle invasive bladder cancer (NMIBC) and 55 muscle invasive bladder cancer (MIBC) patients. There were 32 patients who received cisplatin-based neoadjuvant chemotherapy (NAC) followed by radical cystectomy (RC). Subtraction enrichment combined with immunostaining-fluorescence in situ hybridization (SE-iFISH) strategy was used for CTC/CEC detection. Kaplan-Meier analysis and Cox regression were used to evaluate the overall survival (OS) and recurrence-free survival (RFS). Receiver operator characteristic analysis was used to discriminate NAC sensitivity.CTCs and CECs were related to clinicopathological characteristics. Triploid CTCs, tetraploid CTCs, and total CECs were found to be higher in incipient patients than in relapse patients (P = 0.036, P = 0.019, and P = 0.025, respectively). The number of total CECs and large cell CECs was also associated with advanced tumor stage (P = 0.028 and P = 0.033) and grade (P = 0.028 and P = 0.041). Remarkably, tumor-biomarker-positive CTCs were associated with worse OS and RFS (P = 0.026 and P = 0.038) in NMIBC patients underwent TURBT. CECs cluster was an independent predictor of recurrence in non-high-risk NMIBC patients underwent TURBT (HR = 9.21, P = 0.040). For NAC analysis, pre-NAC tetraploid CTCs and small cell CTCs demonstrated the capability in discriminating NAC-sensitive from insensitive patients. Additionally, tetraploid CTCs and single CTCs elevated post-NAC would indicate chemoresistance.RESULTSCTCs and CECs were related to clinicopathological characteristics. Triploid CTCs, tetraploid CTCs, and total CECs were found to be higher in incipient patients than in relapse patients (P = 0.036, P = 0.019, and P = 0.025, respectively). The number of total CECs and large cell CECs was also associated with advanced tumor stage (P = 0.028 and P = 0.033) and grade (P = 0.028 and P = 0.041). Remarkably, tumor-biomarker-positive CTCs were associated with worse OS and RFS (P = 0.026 and P = 0.038) in NMIBC patients underwent TURBT. CECs cluster was an independent predictor of recurrence in non-high-risk NMIBC patients underwent TURBT (HR = 9.21, P = 0.040). For NAC analysis, pre-NAC tetraploid CTCs and small cell CTCs demonstrated the capability in discriminating NAC-sensitive from insensitive patients. Additionally, tetraploid CTCs and single CTCs elevated post-NAC would indicate chemoresistance.CTCs and CECs may putatively guide in diagnosis, prognosis prediction, and therapeutic decision-making for bladder cancer.CONCLUSIONCTCs and CECs may putatively guide in diagnosis, prognosis prediction, and therapeutic decision-making for bladder cancer.
To investigate the role of circulating rare cells (CRCs), namely, circulating tumor cells (CTCs) and circulating endothelial cells (CECs), in aiding early intervention, treatment decision, and prognostication in bladder cancer. A total of 196 patients with pathologically confirmed bladder cancer, namely, 141 non-muscle invasive bladder cancer (NMIBC) and 55 muscle invasive bladder cancer (MIBC) patients. There were 32 patients who received cisplatin-based neoadjuvant chemotherapy (NAC) followed by radical cystectomy (RC). Subtraction enrichment combined with immunostaining-fluorescence hybridization (SE-iFISH) strategy was used for CTC/CEC detection. Kaplan-Meier analysis and Cox regression were used to evaluate the overall survival (OS) and recurrence-free survival (RFS). Receiver operator characteristic analysis was used to discriminate NAC sensitivity. CTCs and CECs were related to clinicopathological characteristics. Triploid CTCs, tetraploid CTCs, and total CECs were found to be higher in incipient patients than in relapse patients ( = 0.036, = 0.019, and = 0.025, respectively). The number of total CECs and large cell CECs was also associated with advanced tumor stage ( = 0.028 and = 0.033) and grade ( = 0.028 and = 0.041). Remarkably, tumor-biomarker-positive CTCs were associated with worse OS and RFS ( = 0.026 and = 0.038) in NMIBC patients underwent TURBT. CECs cluster was an independent predictor of recurrence in non-high-risk NMIBC patients underwent TURBT (HR = 9.21, = 0.040). For NAC analysis, pre-NAC tetraploid CTCs and small cell CTCs demonstrated the capability in discriminating NAC-sensitive from insensitive patients. Additionally, tetraploid CTCs and single CTCs elevated post-NAC would indicate chemoresistance. CTCs and CECs may putatively guide in diagnosis, prognosis prediction, and therapeutic decision-making for bladder cancer.
PurposeTo investigate the role of circulating rare cells (CRCs), namely, circulating tumor cells (CTCs) and circulating endothelial cells (CECs), in aiding early intervention, treatment decision, and prognostication in bladder cancer.MethodsA total of 196 patients with pathologically confirmed bladder cancer, namely, 141 non-muscle invasive bladder cancer (NMIBC) and 55 muscle invasive bladder cancer (MIBC) patients. There were 32 patients who received cisplatin-based neoadjuvant chemotherapy (NAC) followed by radical cystectomy (RC). Subtraction enrichment combined with immunostaining-fluorescence in situ hybridization (SE-iFISH) strategy was used for CTC/CEC detection. Kaplan–Meier analysis and Cox regression were used to evaluate the overall survival (OS) and recurrence-free survival (RFS). Receiver operator characteristic analysis was used to discriminate NAC sensitivity.ResultsCTCs and CECs were related to clinicopathological characteristics. Triploid CTCs, tetraploid CTCs, and total CECs were found to be higher in incipient patients than in relapse patients (P = 0.036, P = 0.019, and P = 0.025, respectively). The number of total CECs and large cell CECs was also associated with advanced tumor stage (P = 0.028 and P = 0.033) and grade (P = 0.028 and P = 0.041). Remarkably, tumor-biomarker-positive CTCs were associated with worse OS and RFS (P = 0.026 and P = 0.038) in NMIBC patients underwent TURBT. CECs cluster was an independent predictor of recurrence in non-high-risk NMIBC patients underwent TURBT (HR = 9.21, P = 0.040). For NAC analysis, pre-NAC tetraploid CTCs and small cell CTCs demonstrated the capability in discriminating NAC-sensitive from insensitive patients. Additionally, tetraploid CTCs and single CTCs elevated post-NAC would indicate chemoresistance.ConclusionCTCs and CECs may putatively guide in diagnosis, prognosis prediction, and therapeutic decision-making for bladder cancer.
Author Cao, Qiang
Zhou, Rui
Yang, Haiwei
Zhou, Zijian
Li, Pengchao
Yu, Hao
Lu, Qiang
Feng, Dexiang
Gu, Min
Yang, Xiao
Lv, Jiancheng
Wu, Qikai
Yuan, Baorui
Han, Jie
AuthorAffiliation 2 Department of Pediatric Urology, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University , Guangzhou , China
1 Department of Urology, The First Affiliated Hospital of Nanjing Medical University , Nanjing , China
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Keywords circulating tumor cells
prognosis
bladder cancer
circulating endothelial cells
neoadjuvant chemosensitivity
Language English
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Reviewed by: Gian Maria Busetto, University of Foggia, Italy; Matteo Ferro, European Institute of Oncology (IEO), Italy
These authors have contributed equally to this work
Edited by: Takeshi Yuasa, Japanese Foundation For Cancer Research, Japan
This article was submitted to Genitourinary Oncology, a section of the journal Frontiers in Oncology
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Snippet To investigate the role of circulating rare cells (CRCs), namely, circulating tumor cells (CTCs) and circulating endothelial cells (CECs), in aiding early...
PurposeTo investigate the role of circulating rare cells (CRCs), namely, circulating tumor cells (CTCs) and circulating endothelial cells (CECs), in aiding...
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SubjectTerms bladder cancer
circulating endothelial cells
circulating tumor cells
neoadjuvant chemosensitivity
Oncology
prognosis
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Title Clinical Application of Circulating Tumor Cells and Circulating Endothelial Cells in Predicting Bladder Cancer Prognosis and Neoadjuvant Chemosensitivity
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