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Biomarker in Urologic Cancer

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A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Biomarkers".

Deadline for manuscript submissions: closed (30 September 2024) | Viewed by 12622

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Special Issue Editor

Dr. Nessn H. Azawi

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Guest Editor

Department of Urology, Zealand University Hospital, Roskilde, Denmark
Interests: diagnosing, treating, and monitoring urological cancer to optimize treatment and prevent overtreatment

Special Issue Information

Dear Colleagues,

Renal cell carcinoma (RCC) is a prevalent malignant kidney tumor. RCC accounts for 137,000 cases in Europe, 76,000 cases in North America, and 403,000 cases globally annually. Primary metastatic RCC is found in approximately 15–20% of patients at diagnosis, while the remaining patients are offered curative treatment to partially or completely remove the affected kidney. However, 15–20% of these patients experience a recurrence within five years of follow-up. Radiological imaging is the gold standard for recurrence detection, with follow-up CT imaging of the thorax and abdomen every six months for two years and then annually for up to 10. Despite these measures, approximately 30% of recurrences occur outside of follow-up protocols, and only 10% of patients with a recurrence have curable tumors. Therefore, improved prognostic tools are necessary to develop more precise surveillance, diagnosis and treatment strategies to improve survival rates.

We welcome original research articles and reviews that present innovative approaches and techniques in the identification and validation of urological biomarkers. Topics of interest may include but are not limited to the evaluation of new biomarkers for urological cancer, the use of imaging techniques for biomarker detection, and the integration of biomarkers into clinical decision-making processes.

The aim of this Special Issue is to provide an up-to-date overview of the latest research on biomarkers in the field of urology, with a particular focus on kidney cancer. We welcome original research articles and reviews that cover a range of research areas, including (but not limited to) radiological and biological biomarkers for the diagnosis, treatment strategy, and surveillance of urological cancer. Our goal is to gather cutting-edge research that explores new approaches to biomarker discovery and validation, and how these biomarkers can be used to improve patient outcomes. We encourage submissions that showcase innovative research methods and techniques that have the potential to advance the field of urological cancer research. We look forward to receiving your contributions.

Dr. Nessn H. Azawi
Guest Editor

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 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.

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Keywords

urological cancer
biomarkers
diagnosis
prognosis
treatment response
surveillance
imaging
molecular
genetics
urine-based biomarkers

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Published Papers (7 papers)

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Research

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11 pages, 945 KiB

Open AccessArticle

Predicting the Diagnosis of Prostate Cancer with a Novel Blood-Based Biomarker: Comparison of Its Performance with Prostate-Specific Antigen

by Johnmesha L. Sanders, Kenneth A. Iczkowski and Girish V. Shah

Cancers 2024, 16(15), 2619; https://doi.org/10.3390/cancers16152619 - 23 Jul 2024

Viewed by 1041

Abstract

The purpose of this study was to assess the efficacy, specificity, and predictive value of a newly discovered biomarker, Zinc finger-like1 protein (referred to as neuroendocrine marker, NEM) for the detection of prostate cancer (PCa). We retrospectively analyzed banked plasma samples from 508 men, with a median age of 67 years (range 48–97), to compare the performance of NEM and PSA in predicting subsequent histologic PCa. The cohort consisted of four groups of patients visiting a urology clinic: (1) patients not diagnosed with either benign prostatic disease or prostate cancer (PCa) were defined as normal; (2) patients diagnosed with benign hyperplasia (BPH) but not PCa; (3) patients with confirmed PCa; and (4) patients with cancer other than PCa. The normal men displayed a mean NEM plasma level of 0.948 ± 0.051 ng/mL, which increased to 1.813 ± 0.315 ng/mL in men with BPH, 86.49 ± 15.51 ng/mL in men with PCa, and 10.47 ± 1.029 ng/mL in men with other Ca. The corresponding concentrations of prostate-specific antigen (PSA) in these subjects were 1.787 ± 0.135, 5.405 ± 0.699, 35.77 ± 11.48 ng/mL, and 8.036 ± 0.518, respectively. Receiver operating characteristic (ROC) curve analysis was performed to compare NEM and PSA performance, and the Jouden Index for each biomarker was calculated to determine cut-off points for each biomarker. The area under the ROC curve to predict PCa was 0.99 for NEM and 0.81 for PSA (p < 0.0001). The cut-off for NEM was at 1.9 ng/mL, with sensitivity of 98% and specificity of 97%. The corresponding PSA values were 4.4 ng/mL, with sensitivity of 76% and specificity of 95%. The predictive value of each biomarker in a patient was matched with his pathologic data to determine the accuracy of each biomarker. NEM was more accurate than PSA in differentiating cancer from benign conditions, such as BPH or prostatitis. In conclusion, NEM was a better predictor of PCa than PSA in patients visiting urology clinics. NEM tests, either alone or in conjunction with other biomarkers, provide a reliable, non-invasive, and inexpensive test to remarkably reduce false positives and thereby reduce the number of diagnostic biopsies and associated painful procedures and the loss of quality of life. Full article

(This article belongs to the Special Issue Biomarker in Urologic Cancer)

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16 pages, 7043 KiB

Open AccessArticle

Circular STAG2 RNA Modulates Bladder Cancer Progression via miR-145-5p/TAGLN2 and Is Considered as a Biomarker for Recurrence

by Chris Du, Wayne C. Waltzer, Jeremy E. Wilusz, Massimiliano Spaliviero, Frank Darras and Victor Romanov

Cancers 2024, 16(5), 978; https://doi.org/10.3390/cancers16050978 - 28 Feb 2024

Viewed by 1318

Abstract

The current study aimed to elucidate the regulatory mechanisms of the circRNA hsa_circ_0139697 (circSTAG2(16–25)) in BCa and to consider the opportunity of using circSTAG2(16–25) isolated from BCa patient urine as a marker for disease development prediction. The selection of this circRNA was determined by the special role of its parental gene STAG2 in BCa biology. The circRNA hsa_circ_0139697 was chosen from 25 STAG2 circRNAs due to its differential expression in the urine of BCa patients and healthy volunteers. Higher levels of circSTAG2(16–25) were detected in urine samples obtained from patients with recurrent tumors. A higher expression of circSTAG2(16–25) was also detected in more tumorigenic BCa cell lines. The overexpression of circSTAG2(16–25) in BCa cells induced the elevation of proliferation, motility, and invasion. To study the mechanisms of circSTAG2(16–25) activity, we confirmed that circSTAG2(16–25) can bind miR-145-5p in vitro as was predicted by bioinformatic search. miR-145-5p was shown to suppress some genes that promoted BCa progression. One of these genes, TAGLN2, encodes the protein Transgelin 2, which plays a role in BCa cell motility and invasion. Therefore, the possible mechanism of action of circSTAG2(16–25) could be sponging the tumor suppressor miR-145-5p, which results in activation of TAGLN2. In addition, circSTAG2(16–25) might be considered as a potential biomarker for recurrence prediction. Full article

(This article belongs to the Special Issue Biomarker in Urologic Cancer)

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13 pages, 1647 KiB

Open AccessArticle

Use of Droplet Digital Polymerase Chain Reaction to Identify Biomarkers for Differentiation of Benign and Malignant Renal Masses

by Joshua P. Hayden, Adam Wiggins, Travis Sullivan, Thomas Kalantzakos, Kailey Hooper, Alireza Moinzadeh and Kimberly Rieger-Christ

Cancers 2024, 16(4), 787; https://doi.org/10.3390/cancers16040787 - 15 Feb 2024

Cited by 1 | Viewed by 1257

Abstract

Several microRNAs (miRNAs) have been identified as cell-free biomarkers for detecting renal cell carcinoma (RCC). Droplet digital polymerase chain reaction (ddPCR) is a unique technology for nucleic acid quantification. It has the potential for superior precision, reproducibility, and diagnostic performance in identifying circulating miRNA biomarkers compared to conventional quantitative real-time PCR (qRT-PCR). This study aims to evaluate the performance of ddPCR compared to qRT- PCR in identifying miRNA biomarkers that differentiate malignant from benign renal masses. Potential biomarkers of RCC were identified from a literature review. RNA was extracted from the plasma of 56 patients. All the samples underwent analysis via ddPCR as well as qRT-PCR, and expression levels were recorded for the following miRNAs: miR-93, -144, -210, -221, and -222. Tumors were grouped into low-grade ccRCC, high-grade ccRCC, papillary RCC, and benign masses (primarily angiomyolipoma). The miRNA miR-210 (p = 0.034) and the combination of miRs-210 and miR-222 (p = 0.003) were expressed at significantly higher rates among those with RCC than those with benign masses, as measured by ddPCR. Using the combination of miR-210 and miR-222, ddPCR identified significant differences between the subgroups: papillary RCC versus benign (p = 0.03), low-grade ccRCC versus benign (p = 0.026), and high-grade ccRCC versus benign (p = 0.002). The only significant difference between these subgroups using qRT-PCR was between high-grade ccRCC and benign (p = 0.045). All the AUCs were significant when comparing each RCC subgroup with benign for both PCR technologies. Using a combination of miR-210 and miR-222, ddPCR identified significant differences between benign and malignant renal masses that were not identified as significant by conventional qRT-PCR. Full article

(This article belongs to the Special Issue Biomarker in Urologic Cancer)

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12 pages, 1615 KiB

Open AccessArticle

Cystoscopy Accuracy in Detecting Bladder Tumors: A Prospective Video-Confirmed Study

by Cathrine Silberg Guldhammer, Juan Luis Vásquez, Vibeke Møllegaard Kristensen, Thomas Norus, Naomi Nadler, Jørgen Bjerggaard Jensen and Nessn Azawi

Cancers 2024, 16(1), 160; https://doi.org/10.3390/cancers16010160 - 28 Dec 2023

Cited by 3 | Viewed by 2783

Abstract

Background: Bladder cancer ranks as the 10th most common cancer globally. The diagnosis of bladder tumors typically involves cystoscopy. Objective: This study aimed to evaluate the sensitivity and specificity of cystoscopy in detecting bladder tumors within a surveillance program following a bladder cancer diagnosis. Design, Setting, and Participants: This study utilized recordings of cystoscopies conducted at the Department of Urology, Zealand University Hospital, between July 2021 and November 2022. Clinical observations were cross-referenced with pathological results or follow-up cystoscopies. Clinically negative cystoscopies were further scrutinized for potential overlooked tumors. Outcome Measurements and Statistical Analysis: Sensitivity and specificity of cystoscopy were assessed through ROC curve analysis. Results and Limitations: A total of 565 cystoscopies were recorded, with 135 indicating clinical positivity. Among 181 cystoscopies with clinically negative results that underwent a follow-up cystoscopy, 17 patients (9.4%) were subsequently diagnosed with bladder cancer, with the lesions identified in the initial cystoscopy. The sensitivity and specificity of cystoscopy in these cases were 81% and 73%, respectively. Conclusion: This trial underscores the underdiagnosis and undertreatment of bladder tumors within the current surveillance program. Additionally, aggressive malignant lesions may be overlooked, heightening the risk of disease progression. Therefore, it is recommended that cystoscopies be complemented by other diagnostic methods to ensure accurate diagnosis and proper patient treatment. Patient Summary: This study involved 316 patients who underwent video-recorded cystoscopies and subsequent follow-up. Of these patients, 181 initially exhibited no clinical signs of bladder cancer. However, upon reviewing the recorded cystoscopy, bladder cancer was identified in 17 patients (9.4%). Full article

(This article belongs to the Special Issue Biomarker in Urologic Cancer)

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18 pages, 8548 KiB

Open AccessArticle

Identification of SPP1 as a Prognostic Biomarker and Immune Cells Modulator in Urothelial Bladder Cancer: A Bioinformatics Analysis

by Taoufik Nedjadi, Mohamed Eldigire Ahmed, Hifzur R. Ansari, Sihem Aouabdi and Jaudah Al-Maghrabi

Cancers 2023, 15(23), 5704; https://doi.org/10.3390/cancers15235704 - 4 Dec 2023

Cited by 2 | Viewed by 2267

Abstract

Secreted phosphoprotein-1 (SPP1) expression is differentially altered in many malignancies and could serve as a potential prognostic biomarker. Recent findings indicated that SPP1 possesses a broader role in bladder cancer (BC) pathogenesis than previously envisioned; however, the underlying mechanisms governing its expression, cellular localization, prognostic value and immune-related role in bladder cancer remain poorly understood. The expression and the prognosis value of SPP1 were assessed using immunohistochemistry (IHC) staining on a tissue microarray. SPP1 expression was correlated with the clinicopathological parameters, and survival analysis was calculated using a Kaplan–Meier plotter. Bioinformatics analysis of TCGA data was queried using UALCAN, CIBERSORT and TIMER datasets to decipher the biological processes enrichment pattern, protein–protein interactions and characterize tumor-infiltrating immune cells, respectively. IHC revealed that SPP1 expression is significantly associated with tumor type, stage, grade and smoking status. The Kaplan–Meier survival curve showed that low SPP1 expression is an unfavorable prognostic indicator in bladder cancer patients (p = 0.02, log-rank). The significant increased expression of the SPP1 level is associated with evident hypomethylation of the gene promoter in cancer compared to normal tissues in the TCGA-bladder dataset. Missense mutation is the most frequent genetic alteration of the SPP1 gene. Protein–protein interactions demonstrated that SPP1 shares the same network with many important genes and is involved in many signaling pathways and biological processes. TIMER reported a significant correlation between SPP1 expression and multiple immune cells infiltration. Furthermore, the expression of SPP1 was found to be positively correlated with a number of immune checkpoint genes such as PD-1 and CTLA4. The current investigation indicates that the SPP1 protein could serve as a prognostic biomarker and merit further investigation to validate its clinical usefulness in patients with bladder cancer. Full article

(This article belongs to the Special Issue Biomarker in Urologic Cancer)

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11 pages, 1523 KiB

Open AccessArticle

Exploring the Characteristics of Circulating Tumor DNA in Pt1a Clear Cell Renal Cell Carcinoma: A Pilot Study

by Hongkyung Kim, Jee Soo Park, Zisun Choi, Seungki Min, Jihyang Park, Saeam Shin, Jong Rak Choi, Seung-Tae Lee and Won Sik Ham

Cancers 2023, 15(13), 3306; https://doi.org/10.3390/cancers15133306 - 23 Jun 2023

Cited by 1 | Viewed by 1569

Abstract

Circulating tumor DNA (ctDNA) is a promising biomarker for clear cell renal cell carcinoma (ccRCC); however, its characteristics in small renal masses of ccRCC remain unclear. In this pilot study, we explored the characteristics of ctDNA in pT1a ccRCC. Plasma samples were collected preoperatively from 53 patients with pT1a ccRCC. The ctDNA of pT1a ccRCC was profiled using next-generation sequencing and compared with that of higher-stage ccRCC. The association of ctDNA in pT1a ccRCC with clinicopathological features was investigated. The positive relationship of mutations between ctDNA and matched tissues was evaluated. In pT1a ccRCC, the ctDNA detection rate, cell-free DNA concentration, and median variant allele frequency were 20.8%, 5.8 ng/mL, and 0.38%, respectively, which were significantly lower than those in metastatic ccRCC. The ctDNA gene proportions in pT1a samples differed from those in metastatic ccRCC samples. The relationships between ctDNA and tumor size, tumor grade, and patient age were not elucidated. The positive concordance between ctDNA and matched tissues was poor for pT1a ccRCC. Strategies are needed to increase sensitivity while eliminating noise caused by clonal hematopoiesis to increase the clinical utility of ctDNA analysis in small renal masses of ccRCC. Full article

(This article belongs to the Special Issue Biomarker in Urologic Cancer)

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Review

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17 pages, 4286 KiB

Open AccessReview

MicroRNA-371a-3p—The Novel Serum Biomarker in Testicular Germ Cell Tumors

by Tim Nestler, Justine Schoch, Gazanfer Belge and Klaus-Peter Dieckmann

Cancers 2023, 15(15), 3944; https://doi.org/10.3390/cancers15153944 - 3 Aug 2023

Cited by 7 | Viewed by 1764

Abstract

Introduction: Testicular germ cell tumors (TGCTs) are a paradigm for the use of serum tumor markers in clinical management. However, conventional markers such as alpha-fetoprotein (AFP), beta-human chorionic gonadotropin (hCG), and lactate dehydrogenase (LDH) have quite limited sensitivities and specificities. Within the last decade, the microRNA-371a-3p (miR371) emerged as a possible new biomarker with promising features. Areas covered: This review covers the typical features as well as possible clinical applications of miR371 in TGCT patients, such as initial diagnosis, therapy monitoring, and follow-up. Additionally, technical issues are discussed. Expert opinion: With a sensitivity of around 90% and specificity >90%, miR371 clearly outperforms the classical serum tumor markers in TGCTs. The unique features of the test involve the potential of modifying recent standards of care in TGCT. In particular, miR371 is expected to aid clinical decision-making in scenarios such as discriminating small testicular TGCT masses from benign ones prior to surgery, assessing equivocal lymphadenopathies, and monitoring chemotherapy results. Likewise, it is expected to make follow-up easier by reducing the intensity of examinations and by sparing imaging procedures. Overall, the data presently available are promising, but further prospective studies are required before the test can be implemented in standard clinical care. Full article

(This article belongs to the Special Issue Biomarker in Urologic Cancer)

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