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Cancers
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Biomarkers in Prostate Cancers
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Biomarkers in Prostate Cancers

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 12517

Special Issue Editor

Prof. Dr. Shigeo Horie

E-Mail Website
Guest Editor
Graduate School of Medicine, Department of Urology, Juntendo University, Tokyo, Japan
Interests: prostate cancer; robotic surgery; genetics; digital therapeutics; testosterone
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Prostate cancer represents a prevalent malignancy among men. The prominent prostate cancer biomarkers encompass prostate-specific antigen (PSA) and its derivatives, which are proteins produced by prostate cells, as well as various genetic markers. These biomarkers play a pivotal role in facilitating the early detection, risk assessment, and monitoring of treatment responses. Recent research endeavors have primarily concentrated on innovative biomarkers capable of distinguishing between aggressive and indolent forms of prostate cancer, thus aiding in treatment decision making. Furthermore, liquid biopsies designed to detect circulating tumor cells or cell-free DNA exhibit a substantial potential for monitoring disease progression and assessing the responses to therapy. Biomarkers, such as the microbiome, miRNA, long non-coding RNAs (lncRNAs), exosomes, and testosterone, may forecasting responses to anticancer treatments, which make them significance in enhancing treatments’ effectiveness and prostate cancer patients’ survival. As our comprehension of the molecular mechanisms underlying prostate cancer advances, the exploration of novel biomarkers has the potential to revolutionize diagnostic and management approaches, ultimately leading to improved patient outcomes.

This Special Issue serves to spotlight the present state of research pertaining to biomarkers in prostate cancer and the future prospects for enhancing diagnosis and treatment.

Prof. Dr. Shigeo Horie
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.

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

  • PSA
  • androgen receptor
  • testosterone
  • DNA damage response
  • polygenic risk score
  • chromosomal aberration
  • telomere
  • MDSC

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Published Papers (6 papers)

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Research

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11 pages, 2207 KiB  
Article
Clinical Outcomes and Prognostic Factors in Nonmetastatic Castration-Resistant Prostate Cancer Treated with Androgen Receptor Signaling Inhibitors Therapy
by Ryo Fujiwara, Shinya Yamamoto, Kosuke Takemura, Takeshi Yuasa, Noboru Numao, Tomohiko Oguchi, Yosuke Yasuda, Yusuke Yoneoka and Junji Yonese
Cancers 2024, 16(15), 2659; https://doi.org/10.3390/cancers16152659 - 26 Jul 2024
Viewed by 1554
Abstract
We conducted a retrospective evaluation of the clinical outcomes and prognostic factors in patients with nonmetastatic castration-resistant prostate cancer (nmCRPC) treated with first-line androgen receptor signaling inhibitors (ARSI) in real-world clinical practice in Japan. Between 2012 and 2023, a total of 127 consecutive [...] Read more.
We conducted a retrospective evaluation of the clinical outcomes and prognostic factors in patients with nonmetastatic castration-resistant prostate cancer (nmCRPC) treated with first-line androgen receptor signaling inhibitors (ARSI) in real-world clinical practice in Japan. Between 2012 and 2023, a total of 127 consecutive patients with nmCRPC received ARSI treatment. Overall survival (OS), metastatic-free survival (MFS), and prostate-specific antigen–progression-free survival (PSA–PFS) from ARSI initiation were assessed using the Kaplan–Meier methodology. Clinical factors associated with OS in nmCRPC were analyzed using the Cox proportional hazards model. Among the patients, 72, 26, 12, and 17 received enzalutamide (ENZ), abiraterone (ABI), apalutamide (APA), and darolutamide (DARO) as first-line therapy. The median OS and MFS for all patients were 79.0 and 42.0 months, respectively. Median PSA–PFS was 27.0, 20.0, 10.0, and 14.0 months for patients treated with ENZ, ABI, APA, and DARO, respectively (p = 0.33). Multivariate analysis revealed that a baseline PSA level ≥ 3.67 ng/mL at ARSI initiation was significantly associated with poorer OS (p = 0.002). ARSI demonstrated favorable efficacy in nmCRPC patients. There were no significant differences in clinical outcomes among different types of ARSI therapy for nmCRP. Elevated baseline PSA at ARSI initiation was significantly associated with poorer OS. Full article
(This article belongs to the Special Issue Biomarkers in Prostate Cancers)
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15 pages, 904 KiB  
Article
snRNAs from Radical Prostatectomy Specimens Have the Potential to Serve as Prognostic Factors for Clinical Recurrence after Biochemical Recurrence in Patients with High-Risk Prostate Cancer
by Hikaru Mikami, Syunya Noguchi, Jun Akatsuka, Hiroya Hasegawa, Kotaro Obayashi, Hayato Takeda, Yuki Endo, Yuka Toyama, Hiroyuki Takei, Go Kimura, Yukihiro Kondo and Toshihiro Takizawa
Cancers 2024, 16(9), 1757; https://doi.org/10.3390/cancers16091757 - 1 May 2024
Viewed by 2021
Abstract
In patients with high-risk prostate cancer (HRPC) after radical prostatectomy (RP), biochemical recurrence (BCR) increases the risk of distant metastasis. Accordingly, additional prognostic biomarkers are required to identify the subpopulation of patients with HRPC who develop clinical recurrence (CR) after BCR. The objective [...] Read more.
In patients with high-risk prostate cancer (HRPC) after radical prostatectomy (RP), biochemical recurrence (BCR) increases the risk of distant metastasis. Accordingly, additional prognostic biomarkers are required to identify the subpopulation of patients with HRPC who develop clinical recurrence (CR) after BCR. The objective of this study was to identify biomarkers in formalin-fixed paraffin-embedded (FFPE) RP samples that are prognostic for CR in patients with HRPC who experience BCR after RP (post-RP BCR). First, we performed a preliminary RNA sequencing analysis to comprehensively profile RNA expression in FFPE RP samples obtained from patients with HRPC who developed CR after post-RP BCR and found that many snRNAs were very abundant in preserved FFPE samples. Subsequently, we used quantitative polymerase chain reaction (qPCR) to compare the expression levels of highly abundant snRNAs in FFPE RP samples from patients with HRPC with and without CR after post-RP BCR (21 CR patients and 46 non-CR patients who had more than 5 years of follow-up after BCR). The qPCR analysis revealed that the expression levels of snRNA RNU1-1/1-2 and RNU4-1 were significantly higher in patients with CR than in patients without CR. These snRNAs were significantly correlated with clinical recurrence-free survival (RFS) in patients with HRPC who experienced post-RP BCR. Furthermore, snRNA RNU1-1/1-2 could serve as an independent prognostic factor for clinical RFS in post-RP BCR of HRPC cases where known prognostic factors (e.g., Gleason score) cannot distinguish between CR and non-CR patients. Our findings provide new insights into the involvement of snRNAs in prostate cancer progression. Full article
(This article belongs to the Special Issue Biomarkers in Prostate Cancers)
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13 pages, 1185 KiB  
Article
The Detection and Negative Reversion of Circulating Tumor Cells as Prognostic Biomarkers for Metastatic Castration-Resistant Prostate Cancer with Bone Metastases Treated by Enzalutamide
by So Nakamura, Masayoshi Nagata, Naoya Nagaya, Takeshi Ashizawa, Hisashi Hirano, Yan Lu, Hisamitsu Ide and Shigeo Horie
Cancers 2024, 16(4), 772; https://doi.org/10.3390/cancers16040772 - 13 Feb 2024
Cited by 3 | Viewed by 1890
Abstract
Enzalutamide is a second-generation androgen receptor inhibitor that increases overall survival (OS) rates in patients with metastatic castration-resistant prostate cancer (mCRPC). This study evaluates the efficacy of circulating tumor cell (CTC) status as a prognostic biomarker following enzalutamide administration. A retrospective subgroup analysis [...] Read more.
Enzalutamide is a second-generation androgen receptor inhibitor that increases overall survival (OS) rates in patients with metastatic castration-resistant prostate cancer (mCRPC). This study evaluates the efficacy of circulating tumor cell (CTC) status as a prognostic biomarker following enzalutamide administration. A retrospective subgroup analysis and prognostic survey were conducted on 43 patients with mCRPC and bone metastases treated in Juntendo University-affiliated hospitals from 2015 to 2022. Patients were treated with 160 mg enzalutamide daily. CTC analyses on blood samples were performed regularly before and every three months after treatment. The relationship between the patients’ clinical factors and the OS rate was analyzed using the log-rank test; the median OS was 37 months. Patients with no detected CTCs at baseline showed significantly longer OS than those with detectable CTCs at baseline. Furthermore, patients demonstrating negative reversion of CTCs during enzalutamide treatment had significantly longer OS than patients with CTC-positivity. Two biomarkers—higher hemoglobin at baseline and achieving negative reversion of CTCs—were significantly associated with prolonged OS. This study suggests that patients achieving CTC-negative reversion during treatment for mCRPC with bone metastases exhibit improved long-term OS. Chronological measurement of CTC status might be clinically useful in the treatment of mCRPC. Full article
(This article belongs to the Special Issue Biomarkers in Prostate Cancers)
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Review

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27 pages, 2839 KiB  
Review
Evidence of the Link between Stroma Remodeling and Prostate Cancer Prognosis
by Davide Vecchiotti, Letizia Clementi, Emanuele Cornacchia, Mauro Di Vito Nolfi, Daniela Verzella, Daria Capece, Francesca Zazzeroni and Adriano Angelucci
Cancers 2024, 16(18), 3215; https://doi.org/10.3390/cancers16183215 - 21 Sep 2024
Viewed by 2116
Abstract
Prostate cancer (PCa), the most commonly diagnosed cancer in men worldwide, is particularly challenging for oncologists when a precise prognosis needs to be established. Indeed, the entire clinical management in PCa has important drawbacks, generating an intense debate concerning the possibility to individuate [...] Read more.
Prostate cancer (PCa), the most commonly diagnosed cancer in men worldwide, is particularly challenging for oncologists when a precise prognosis needs to be established. Indeed, the entire clinical management in PCa has important drawbacks, generating an intense debate concerning the possibility to individuate molecular biomarkers able to avoid overtreatment in patients with pathological indolent cancers. To date, the paradigmatic change in the view of cancer pathogenesis prompts to look for prognostic biomarkers not only in cancer epithelial cells but also in the tumor microenvironment. PCa ecology has been defined with increasing details in the last few years, and a number of promising key markers associated with the reactive stroma are now available. Here, we provide an updated description of the most biologically significant and cited prognosis-oriented microenvironment biomarkers derived from the main reactive processes during PCa pathogenesis: tissue adaptations, inflammatory response and metabolic reprogramming. Proposed biomarkers include factors involved in stromal cell differentiation, cancer-normal cell crosstalk, angiogenesis, extracellular matrix remodeling and energy metabolism. Full article
(This article belongs to the Special Issue Biomarkers in Prostate Cancers)
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16 pages, 296 KiB  
Review
Usefulness of Tissue Biomarkers versus Prostate-Specific Membrane Antigen-Positron Emission Tomography for Prostate Cancer Biochemical Recurrence after Radical Prostatectomy
by Gabriela Vera, Pablo A. Rojas, Joseph B. Black and Ignacio F. San Francisco
Cancers 2024, 16(16), 2879; https://doi.org/10.3390/cancers16162879 - 19 Aug 2024
Viewed by 1393
Abstract
Despite curative-intent local therapy, approximately 27% to 53% of prostate cancer (PCa) patients experience prostate-specific antigen (PSA) recurrence, known as biochemical recurrence (BCR). BCR significantly raises the risk of PCa-related morbidity and mortality, yet there is no consensus on optimal management. Prostate-specific membrane [...] Read more.
Despite curative-intent local therapy, approximately 27% to 53% of prostate cancer (PCa) patients experience prostate-specific antigen (PSA) recurrence, known as biochemical recurrence (BCR). BCR significantly raises the risk of PCa-related morbidity and mortality, yet there is no consensus on optimal management. Prostate-specific membrane antigen-positron emission tomography (PSMA PET) has emerged as highly sensitive imaging, distinguishing local recurrences from distant metastases, crucially influencing treatment decisions. Genomic biomarkers such as Decipher, Prolaris, and Oncotype DX contribute to refining recurrence risk profiles, guiding decisions on intensifying adjuvant therapies, like radiotherapy and androgen deprivation therapy (ADT). This review assesses PSMA PET and biomarker utility in post-radical prostatectomy BCR scenarios, highlighting their impact on clinical decision-making. Despite their promising roles, the routine integration of biomarkers is limited by availability and cost, requiring further evidence. PSMA PET remains indispensable for restaging and treatment evaluation in these patients. Integrating biomarkers and PSMA PET promises to optimize personalized management strategies for BCR, though more comprehensive consensus-building studies are needed to define their standardized utility in clinical practice. Full article
(This article belongs to the Special Issue Biomarkers in Prostate Cancers)

Other

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17 pages, 841 KiB  
Systematic Review
Biomarkers for Pre-Treatment Risk Stratification of Prostate Cancer Patients: A Systematic Review
by José Pedro Sequeira, Sofia Salta, Rui Freitas, Rafael López-López, Ángel Díaz-Lagares, Rui Henrique and Carmen Jerónimo
Cancers 2024, 16(7), 1363; https://doi.org/10.3390/cancers16071363 - 30 Mar 2024
Cited by 4 | Viewed by 2737
Abstract
Background: Prostate cancer (PCa) is one of the most frequently occurring malignancies. Although most cases are not life-threatening, approximately 20% endure an unfavorable outcome. PSA-based screening reduced mortality but at the cost of an increased overdiagnosis/overtreatment of low-risk (lrPCa) and favorable intermediate-risk (firPCa) [...] Read more.
Background: Prostate cancer (PCa) is one of the most frequently occurring malignancies. Although most cases are not life-threatening, approximately 20% endure an unfavorable outcome. PSA-based screening reduced mortality but at the cost of an increased overdiagnosis/overtreatment of low-risk (lrPCa) and favorable intermediate-risk (firPCa) PCa. PCa risk-groups are usually identified based on serum Prostate-Specific Antigen (PSA), the Gleason score, and clinical T stage, which have consistent although variable specificity or subjectivity. Thus, more effective and specific tools for risk assessment are needed, ideally making use of minimally invasive methods such as liquid biopsies. In this systematic review we assessed the clinical potential and analytical performance of liquid biopsy-based biomarkers for pre-treatment risk stratification of PCa patients. Methods: Studies that assessed PCa pre-treatment risk were retrieved from PubMed, Scopus, and MedLine. PCa risk biomarkers were analyzed, and the studies’ quality was assessed using the QUADAS-2 tool. Results: The final analysis comprised 24 full-text articles, in which case-control studies predominated, mostly reporting urine-based biomarkers (54.2%) and biomarker quantification by qPCR (41.7%). Categorization into risk groups was heterogeneous, predominantly making use of the Gleason score. Conclusion: This systematic review unveils the substantial clinical promise of using circulating biomarkers in assessing the risk for prostate cancer patients. However, the standardization of groups, categories, and biomarker validation are mandatory before this technique can be implemented. Circulating biomarkers might represent a viable alternative to currently available tools, obviating the need for tissue biopsies, and allowing for faster and more cost-effective testing, with superior analytical performance, specificity, and reproducibility. Full article
(This article belongs to the Special Issue Biomarkers in Prostate Cancers)
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