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Cancers
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Liquid Biopsy of Genitourinary Tumors
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Liquid Biopsy of Genitourinary Tumors

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Methods and Technologies Development".

Deadline for manuscript submissions: closed (20 May 2023) | Viewed by 6049

Special Issue Editors

Prof. Dr. Ghulam Nabi

E-Mail Website
Guest Editor
1. Department of Urology, University of Dundee, Scotland DD1 9SY, UK
2. Institute of Medical Science and Technology, University of Dundee, Scotland DD1 9SY, UK
Interests: urological cancers; biomarkers; surgical technology; lasers; raman spectroscopy; biophotonics; elastography; focused ultrasound surgery (FUS)
Dr. Alagarsamy Srinivasan

E-Mail Website
Guest Editor
Formerly Associated with Thomas Jefferson University & Center for Prostate Disease Research, Uniformed Services University, Bethesda, MD 20814, USA
Interests: liquid biopsy; tumor antigens; autoantibodies; multi-omics; prognostic biomarkers; diagnostic biomarkers; cancer vaccines; immunotherapy
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Sundarasamy Mahalingam

E-Mail Website
Guest Editor
Department of Biotechnology, National Cancer Tissue Biobank, Indian Indstitute of Technology Madras, Chennai 600036, India
Interests: signaling mechanism in cancer cells; genomics; biomarkers
Dr. Shiv Srivastava

E-Mail Website
Guest Editor
Department of Biochemistry and Molecular & Cellular Biology, Georgetown University Medical Center, Washignton, DC 20057, USA
Interests: prostate cancer; biomarkers; therapeutic targets; cancer driver genes

Special Issue Information

Dear Colleagues,

A look at the evolution of science in the past century reveals an interesting pattern. Specifically, scientific progress went hand-in-hand with the technological advances during this period. This is evident in multiple disciplines of life sciences, including microbiology and tumor biology. The notable technical advances in the recent past have involved nucleic acids (DNA and RNA-mRNA, miRNA and lnRNA), proteins, peptides and metabolites. Both biophysical and biochemical methods including next-gen nucleic acid sequencing and mass spectrometry narrowed the analyses from cells and macromolecules to the nanoscale level. These advances have also enabled their utilitization in the analysis of specimens from patients, resulting in the identification of bona fide biomarkers of specific disease.

In our view, this Special Issue titled “Liquid Biopsy in Genitourinary Tumors” is timely. It is worth mentioning that both diagnostics and treatment of cancers, in general, have greatly benefited from the discovery of biomarkers through multi-omics and other technologies. The specimens from patients for analysis traditionally included biopsy tissues. Later, this was expanded to include blood (sera and plasma) and urine. The liquid biopsy, as is known, includes specimens from multiple sources such as blood, urine, saliva and cerebrospinal fluid (CSF). The components for analysis range from cells, exosomes, circulating cell-free DNA, RNA proteins, peptides and metabolites. The rationale for the analysis of body fluids from patients is that the analytical components may serve as biomarkers of the disease and disease status in real time, e.g., post-treatment follow-up. In addition, biomarkers can also serve as targets for treatment. A major advantage of liquid biopsy is that it is minimally invasive and can be used to easily collect samples. Further, this can also be repeated for patients as often as needed without a negative effect.

It is our aim that this Special Issue will publish articles authored by investigators highlighting the recent advances in genitourinary tumors from both diagnostic and treatment perspectives.

Prof. Dr. Ghulam Nabi
Dr. Alagarsamy Srinivasan
Prof. Dr. Sundarasamy Mahalingam
Dr. Shiv Srivastava
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • biomarkers
  • exosomes
  • circulating cell-free DNA
  • multi-omics
  • targets for treatment
  • sera/plasma

Published Papers (5 papers)

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Research

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12 pages, 740 KiB  
Article
Filamin A Is a Prognostic Serum Biomarker for Differentiating Benign Prostatic Hyperplasia from Prostate Cancer in Caucasian and African American Men
by Nischal Mahaveer Chand, Poornima K. Tekumalla, Matt T. Rosenberg, Albert Dobi, Amina Ali, Gregory M. Miller, Juan J. Aristizabal-Henao, Elder Granger, Stephen J. Freedland, Mark D. Kellogg, Shiv Srivastava, David G. McLeod, Niven R. Narain and Michael A. Kiebish
Cancers 2024, 16(4), 712; https://doi.org/10.3390/cancers16040712 - 8 Feb 2024
Viewed by 948
Abstract
Prostate cancer represents a significant health risk to aging men, in which diagnostic challenges to the identification of aggressive cancers remain unmet. Prostate cancer screening is driven by the prostate-specific antigen (PSA); however, in men with benign prostatic hyperplasia (BPH) due to an [...] Read more.
Prostate cancer represents a significant health risk to aging men, in which diagnostic challenges to the identification of aggressive cancers remain unmet. Prostate cancer screening is driven by the prostate-specific antigen (PSA); however, in men with benign prostatic hyperplasia (BPH) due to an enlarged prostate and elevated PSA, PSA’s screening utility is diminished, resulting in many unnecessary biopsies. To address this issue, we previously identified a cleaved fragment of Filamin A (FLNA) protein (as measured with IP-MRM mass spectrometry assessment as a prognostic biomarker for stratifying BPH from prostate cancer and subsequently evaluated its expanded utility in Caucasian (CA) and African American (AA) men. All men had a negative digital rectal examination (DRE) and PSA between 4 and 10 ng/mL and underwent prostate biopsy. In AA men, FLNA serum levels exhibited diagnostic utility for stratifying BPH from patients with aggressive prostate cancer (0.71 AUC and 12.2 OR in 48 men with BPH and 60 men with PCa) and outperformed PSA (0.50 AUC, 2.2 OR). In CA men, FLNA serum levels also exhibited diagnostic utility for stratifying BPH from patients with aggressive prostate cancer (0.74 AUC and 19.4 OR in 191 men with BPH and 109 men with PCa) and outperformed PSA (0.46 AUC, 0.32 OR). Herein, we established FLNA alone as a serum biomarker for stratifying men with BPH vs. those with high Gleason (7–10) prostate cancers compared to the current diagnostic paradigm of using PSA. This approach demonstrates clinical actionability of FLNA alone without the requirement of prostate volume measurement as a test with utility in AA and CA men and represents a significant opportunity to decrease the number of unnecessary biopsies in aggressive prostate cancer diagnoses. Full article
(This article belongs to the Special Issue Liquid Biopsy of Genitourinary Tumors)
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14 pages, 2457 KiB  
Communication
Polyploid Giant Cancer Cells Are Frequently Found in the Urine of Prostate Cancer Patients
by Laura Nalleli Garrido Castillo, Julien Anract, Nicolas Barry Delongchamps, Olivier Huillard, Fatima BenMohamed, Alessandra Decina, Thierry Lebret, Roger Dachez and Patrizia Paterlini-Bréchot
Cancers 2023, 15(13), 3366; https://doi.org/10.3390/cancers15133366 - 27 Jun 2023
Cited by 1 | Viewed by 1544
Abstract
Prostate cancer is the third cause of cancer-related deaths in men. Its early and reliable diagnosis is still a public health issue, generating many useless prostate biopsies. Prostate cancer cells detected in urine could be the target of a powerful test but they [...] Read more.
Prostate cancer is the third cause of cancer-related deaths in men. Its early and reliable diagnosis is still a public health issue, generating many useless prostate biopsies. Prostate cancer cells detected in urine could be the target of a powerful test but they are considered too rare. By using an approach targeting rare cells, we have analyzed urine from 45 patients with prostate cancer and 43 healthy subjects under 50 y.o. We observed a relevant number of giant cells in patients with cancer. Giant cells, named Polyploid Giant Cancer Cells (PGCC), are thought to be involved in tumorigenesis and treatment resistance. We thus performed immune-morphological studies with cancer-related markers such as α-methylacyl-CoA racemase (AMACR), prostate-specific membrane antigen (PSMA), and telomerase reverse transcriptase (TERT) to understand if the giant cells we found are PGCC or other urinary cells. We found PGCC in the urine of 22 patients, including those with early-stage prostate cancer, and one healthy subject. Although these results are preliminary, they provide, for the first time, clinical evidence that prostate cancers release PGCC into the urine. They are expected to stimulate further studies aimed at understanding the role of urinary PGCC and their possible use as a diagnostic tool and therapeutic target. Full article
(This article belongs to the Special Issue Liquid Biopsy of Genitourinary Tumors)
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Review

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10 pages, 261 KiB  
Review
Advancing GCT Management: A Review of miR-371a-3p and Other miRNAs in Comparison to Traditional Serum Tumor Markers
by Crystal L. Seales, Dhruv Puri, Nuphat Yodkhunnatham, Kshitij Pandit, Kit Yuen, Sarah Murray, Jane Smitham, John T. Lafin and Aditya Bagrodia
Cancers 2024, 16(7), 1379; https://doi.org/10.3390/cancers16071379 - 31 Mar 2024
Viewed by 666
Abstract
MicroRNAs, short non-protein coding RNAs, are overexpressed in GCTs. Circulating levels of germ cell tumor (GCT)-associated miRNAs, such as miR-371a-3p, can be utilized as efficient and cost-effective alternatives in diagnosing and managing patients presenting with GCTs. This quality of miRNAs has demonstrated favorable [...] Read more.
MicroRNAs, short non-protein coding RNAs, are overexpressed in GCTs. Circulating levels of germ cell tumor (GCT)-associated miRNAs, such as miR-371a-3p, can be utilized as efficient and cost-effective alternatives in diagnosing and managing patients presenting with GCTs. This quality of miRNAs has demonstrated favorable performance characteristics as a reliable blood-based biomarker with high diagnostic accuracy compared to current serum tumor markers (STMs), including α-fetoprotein (AFP), beta human chorionic gonadotropin (β-hCG), and lactate dehydrogenase (LDH). The conventional STMs exhibit limited specificity and sensitivity. Potential clinical implications of miRNAs include impact on de-escalating or intensifying treatment, detecting recurrence at earlier stages, and lessening the necessity of cross-sectional imaging or invasive tissue biopsy for non-teratomatous GCTs. Here, we also highlight the outstanding issues that must be addressed prior to clinical implementation. Standards for measuring circulating miRNAs and determining ideal cutoff values are essential for integration into current clinical guidelines. Full article
(This article belongs to the Special Issue Liquid Biopsy of Genitourinary Tumors)
15 pages, 293 KiB  
Review
Clinical Biofluid Assays for Prostate Cancer
by Talaibek Borbiev, Indu Kohaar and Gyorgy Petrovics
Cancers 2024, 16(1), 165; https://doi.org/10.3390/cancers16010165 - 28 Dec 2023
Cited by 1 | Viewed by 1056
Abstract
This mini review summarizes the currently available clinical biofluid assays for PCa. The second most prevalent cancer worldwide is PCa. PCa is a heterogeneous disease, with a large percentage of prostate tumors being indolent, and with a relatively slow metastatic potential. However, due [...] Read more.
This mini review summarizes the currently available clinical biofluid assays for PCa. The second most prevalent cancer worldwide is PCa. PCa is a heterogeneous disease, with a large percentage of prostate tumors being indolent, and with a relatively slow metastatic potential. However, due to the high case numbers, the absolute number of PCa-related deaths is still high. In fact, it causes the second highest number of cancer deaths in American men. As a first step for the diagnosis of PCa, the PSA test has been widely used. However, it has low specificity, which results in a high number of false positives leading to overdiagnosis and overtreatment. Newer derivatives of the original PSA test, including the Food and Drug Administration (FDA)-approved 4K (four kallikreins) and the PHI (Prostate Health Index) blood tests, have higher specificities. Tissue-based PCa tests are problematic as biopsies are invasive and have limited accuracy due to prostate tumor heterogeneity. Liquid biopsies offer a minimally or non-invasive choice for the patients, while providing a more representative reflection of the spatial heterogeneity in the prostate. In addition to the abovementioned blood-based tests, urine is a promising source of PCa biomarkers, offering a supplementary avenue for early detection and improved tumor classification. Four urine-based PCa tests are either FDA- or CLIA-approved: PCA3 (PROGENSA), ExoDX Prostate Intelliscore, MiPS, and SelectMDx. We will discuss these urine-based, as well as the blood-based, clinical PCa tests in more detail. We also briefly discuss a few promising biofluid marker candidates (DNA methylation, micro-RNAs) which are not in clinical application. As no single assay is perfect, we envision that a combination of biomarkers, together with imaging, will become the preferred practice. Full article
(This article belongs to the Special Issue Liquid Biopsy of Genitourinary Tumors)

Other

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20 pages, 3043 KiB  
Systematic Review
Comparative Assessment of Different Ultrasound Technologies in the Detection of Prostate Cancer: A Systematic Review and Meta-Analysis
by Dareen Alghamdi, Neil Kernohan, Chunhui Li and Ghulam Nabi
Cancers 2023, 15(16), 4105; https://doi.org/10.3390/cancers15164105 - 15 Aug 2023
Cited by 2 | Viewed by 1296
Abstract
The present study aimed to assess the diagnostic test accuracy of different ultrasound scanning technologies in the detection of prostate cancer. A systematic search was conducted using the Cochrane Guidelines for Screening and Diagnostic Tests. We performed a systematic search in the international [...] Read more.
The present study aimed to assess the diagnostic test accuracy of different ultrasound scanning technologies in the detection of prostate cancer. A systematic search was conducted using the Cochrane Guidelines for Screening and Diagnostic Tests. We performed a systematic search in the international databases PubMed, Medline, Ovid, Embase and Cochrane Library. Searches were designed to find all studies that evaluated Micro-US, mpUS, SWE and CEUS as the main detection modalities for prostate cancer. This study was registered with Research Registry of systematic review and meta-analysis. The QUADAS-2 tool was utilized to perform quality assessment and bias analysis. The literature search generated 1376 studies. Of these, 320 studies were screened for eligibility, with 1056 studies being excluded. Overall, 26 studies with a total of 6370 patients met the inclusion criteria. The pooled sensitivity for grayscale, CEUS, SWE, Micro-US and mpUS modalities were 0.66 (95% CI 0.54–0.73) 0.73 (95% CI 0.58–0.88), 0.82 (95% CI 0.75–0.90), 0.85 (95% CI 0.76–0.94) and 0.87 (95% CI 0.71–1.03), respectively. Moreover, the pooled specificity for grayscale, CEUS, SWE, Micro-US and mpUS modalities were 0.56 (95% CI 0.21–0.90), 0.78 (95% CI 0.67–0.88), 0.76 (95% CI 0.65–0.88), 0.43 (95% CI 0.28–0.59) and 0.68 (95% CI 0.54–0.81), respectively. In terms of sensitivity, substantial heterogeneity between studies was detected (I2 = 72%, p = 0.000 < 0.05). In relation to specificity, extreme heterogeneity was detected (I2 = 93%, p = 0.000 < 0.05). Some studies proved that advanced ultrasound modalities such as mpUS, Micro-US, shear-wave elastography, contrast enhanced and micro-ultrasound are promising methods for the detection of prostate cancer. Full article
(This article belongs to the Special Issue Liquid Biopsy of Genitourinary Tumors)
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