Circulating Cell-Free DNA in Liquid Biopsies as Potential Biomarker for Bladder Cancer: A Systematic Review

Herranz, Raquel; Oto, Júlia; Plana, Emma; Fernández-Pardo, Álvaro; Cana, Fernando; Martínez-Sarmiento, Manuel; Donoso, C.D. Vera; España, Francisco; Medina, Pilar

doi:10.3390/cancers13061448

Cited by 11 publications

(3 citation statements)

References 74 publications

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“…Apart from CTCs/CECs, circulating free DNA (cfDNA) and exosomes are also significant targets for liquid biopsy (13). In bladder cancer patients, cfDNA and exosomes have been implicated in indicating cancer progression or even predicting the drug sensitivity (14,15).…”

Section: Introductionmentioning

confidence: 99%

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

Xiao

Zhou

et al. 2022

Front. Oncol.

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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.

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Section: Introductionmentioning

confidence: 99%

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

Xiao

Zhou

et al. 2022

Front. Oncol.

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“…Urinary genomics focuses on the analysis of genetic material (DNA and RNA) in urine samples. One of the compounds that can be analysed by urine genomics is cell-free DNA (cfDNA) [61,62]. This is DNA that is released into the bloodstream and eventually excreted in the urine.…”

Section: Urinary Metabolic Biomarkers In Cancer Diagnosticsmentioning

confidence: 99%

Urinary Metabolic Biomarker Profiling for Cancer Diagnosis by Terahertz Spectroscopy: Review and Perspective

Abina,

Korošec,

Puc

et al. 2023

Photonics

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In the last decade, terahertz (THz) technologies have been introduced to the detection, identification, and quantification of biomolecules in various biological samples. This review focuses on substances that represent important biomarkers in the urine associated with various cancers and their treatments. From a diagnostic point of view, urine liquid biopsy is particularly important because it allows the non-invasive and rapid collection of large volumes of samples. In this review, the THz spectral responses of substances considered metabolic biomarkers in urine and obtained in previous studies are collected. In addition, the findings from the relatively small number of prior studies that have already been carried out on urine samples are summarised. In this context, we also present the different THz methods used for urine analysis. Finally, a brief discussion is given, presenting perspectives for future research in this field, interpreted based on the results of previous studies. This work provides important information on the further application of THz techniques in biomedicine for detecting and monitoring urinary biomarkers for various diseases, including cancer.

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“…Liquid biopsy is a revolutionary technique that allows the detection of circulating tumor cells, nucleic acids, and exosomes released by the tumor into the bloodstream or other biological fluids such as urine. Accordingly, efforts are being made to establish liquid biopsy as an alternative to tumor percutaneous biopsy, which is highly invasive, hazardous and cannot be performed when clinical conditions worsen or when the tumor is inaccessible [ 5 , 6 ]. In particular, urine represents the ideal sample to develop novel tools to diagnose RCC and monitor the follow-up and prognosis of RCC patients.…”

Section: Introductionmentioning

confidence: 99%

Identification of miR-20a-5p as Robust Normalizer for Urine microRNA Studies in Renal Cell Carcinoma and a Profile of Dysregulated microRNAs

Oto

Herranz

Plana

et al. 2021

IJMS

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Renal cell carcinoma (RCC) is the third most frequent urinary malignancy and one of the most lethal. Current diagnostic and follow-up techniques are harmful and unspecific in low-grade tumors. Novel minimally invasive markers such as urine microRNAs (miRNAs) are under study. However, discrepancies arise among studies in part due to lack of consent regarding normalization. We aimed to identify the best miRNA normalizer for RCC studies performed in urine samples together with a miRNA profile with diagnostic value and another for follow-up. We evaluated the performance of 120 candidate miRNAs in the urine of 16 RCC patients and 16 healthy controls by RT-qPCR followed by a stability analysis with RefFinder. In this screening stage, miR-20a-5p arose as the most stably expressed miRNA in RCC and controls, with a good expression level. Its stability was validated in an independent cohort of 51 RCC patients and 32 controls. Using miR-20a-5p as normalizer, we adjusted and validated a diagnostic model for RCC with three miRNAs (miR-200a-3p, miR-34a-5p and miR-365a-3p) (AUC = 0.65; Confidence Interval 95% [0.51, 0.79], p = 0.043). let-7d-5p and miR-205-5p were also upregulated in patients compared to controls. Comparing RCC samples before surgery and fourteen weeks after, we identified let-7d-5p, miR-152-3p, miR-30c-5p, miR-362-3p and miR-30e-3p as potential follow-up profile for RCC. We identified validated targets of most miRNAs in the renal cell carcinoma pathway. This is the first study that identifies a robust normalizer for urine RCC miRNA studies, miR-20a-5p, which may allow the comparison of future studies among laboratories. Once confirmed in a larger independent cohort, the miRNAs profiles identified may improve the non-invasive diagnosis and follow-up of RCC.

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Circulating Cell-Free DNA in Liquid Biopsies as Potential Biomarker for Bladder Cancer: A Systematic Review

Cited by 11 publications

References 74 publications

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

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

Urinary Metabolic Biomarker Profiling for Cancer Diagnosis by Terahertz Spectroscopy: Review and Perspective

Identification of miR-20a-5p as Robust Normalizer for Urine microRNA Studies in Renal Cell Carcinoma and a Profile of Dysregulated microRNAs

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