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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Oncology".

Deadline for manuscript submissions: closed (31 August 2022) | Viewed by 16599

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Dr. Mireia Olivan

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Guest Editor

1. Translational Oncology Laboratory, Anatomy Unit, Department of Pathology and Experimental Therapy, School of Medicine, Universitat de Barcelona (UB), Feixa Llarga, s/n, 08907 L’Hospitalet de Llobregat, Spain
2. Oncobell Program, Bellvitge Biomedical Research Institute (IDIBELL), Gran Via de l'Hospitalet 199, 08908 L’Hospitalet de Llobregat, Spain
Interests: prostate cancer; microRNA; bone metastasis; prognosis biomarkers; exosomes; biofluids

Special Issue Information

Dear Colleagues,

Although the survival of prostate cancer (PCa) patients has improved over the last two decades, PCa remains the most prevalent cancer in men with almost one and a half million of new cases diagnosed in 2020 among this population. When the disease is diagnosed confined to the organ, it is curable, however once the tumor disseminates to distant organs such as bone, the prognosis drastically worsens. Generally, patients with advanced stage PCa are treated with androgen deprivation therapy (ADT). Unfortunately, in most cases ADT is only effective temporarily; PCa gradually acquires resistance to androgen deprivation and eventually becomes castration resistant prostate cancer (CRPC), often associated to tumor dissemination. Bone metastasis is a common complication of cancer and occurs in around 70% of patients with metastatic PCa. Bone metastasis represents a scenario difficult to treat due to pain, fracture risk and decreased quality of life; importantly, tumors become generally incurable.

This type of cancer is frequently multifocal, and such heterogeneity has an impact on PCa progression since individual cancer cells contained within the tumor may have distinct genomic profiles and, consequently, influence the efficacy of current therapies.

This Special issue aims to expand our knowledge of the molecular bases of the PCa progression, thus opening a range of possible new therapeutic targets and predictive markers of poor prognosis that will lead us to improve the treatment of patients with advanced disease. Experimental studies in vitro and in vivo models, review articles are all welcome for consideration.

Dr. Mireia Olivan
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 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.

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Keywords

prostate cancer
CRPC
progression
PCa dissemination
bone metastasis
therapeutic targets
prognostic biomarkers

Published Papers (6 papers)

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Research

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15 pages, 3311 KiB

Open AccessArticle

Lymphatic Dissemination in Prostate Cancer: Features of the Transcriptomic Profile and Prognostic Models

by Elena A. Pudova, Anastasiya A. Kobelyatskaya, Irina V. Katunina, Anastasiya V. Snezhkina, Maria S. Fedorova, Vladislav S. Pavlov, Ildar R. Bakhtogarimov, Margarita S. Lantsova, Sergey P. Kokin, Kirill M. Nyushko, Boris Ya. Alekseev, Dmitry V. Kalinin, Nataliya V. Melnikova, Alexey A. Dmitriev, George S. Krasnov and Anna V. Kudryavtseva

Int. J. Mol. Sci. 2023, 24(3), 2418; https://doi.org/10.3390/ijms24032418 - 26 Jan 2023

Cited by 4 | Viewed by 1631

Abstract

Radical prostatectomy is the gold standard treatment for prostate cancer (PCa); however, it does not always completely cure PCa, and patients often experience a recurrence of the disease. In addition, the clinical and pathological parameters used to assess the prognosis and choose further tactics for treating a patient are insufficiently informative and need to be supplemented with new markers. In this study, we performed RNA-Seq of PCa tissue samples, aimed at identifying potential prognostic markers at the level of gene expression and miRNAs associated with one of the key signs of cancer aggressiveness—lymphatic dissemination. The relative expression of candidate markers was validated by quantitative PCR, including an independent sample of patients based on archival material. Statistically significant results, derived from an independent set of samples, were confirmed for miR-148a-3p and miR-615-3p, as well as for the CST2, OCLN, and PCAT4 genes. Considering the obtained validation data, we also analyzed the predictive value of models based on various combinations of identified markers using algorithms based on machine learning. The highest predictive potential was shown for the “CST2 + OCLN + pT” model (AUC = 0.863) based on the CatBoost Classifier algorithm. Full article

(This article belongs to the Special Issue Advances in Agressive Prostate Cancer)

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10 pages, 1407 KiB

Open AccessArticle

Follow-Up Biomarkers in the Evolution of Prostate Cancer, Levels of S100A4 as a Detector in Plasma

by Maria Jesus Alvarez-Cubero, Elena Arance, Esperanza de Santiago, Pilar Sanchez, Maria Rosario Sepúlveda, Raquel Marrero, Jose Antonio Lorente, Jose Maria Gonzalez-Cabezuelo, Sergio Cuenca-Lopez, Jose Manuel Cozar, Fernando Vazquez-Alonso and Luis Javier Martinez-Gonzalez

Int. J. Mol. Sci. 2023, 24(1), 547; https://doi.org/10.3390/ijms24010547 - 29 Dec 2022

Cited by 3 | Viewed by 1955

Abstract

The management and screening of prostate cancer (PC) is still the main problem in clinical practice. In this study, we investigated the role of aggressiveness genetic markers for PC stratification. We analyzed 201 plasma samples from PC patients and controls by digital PCR. For selection and validation, 26 formalin-fixed paraffin-embedded tissues, 12 fresh tissues, and 24 plasma samples were characterized by RNA-Seq, immunochemistry, immunofluorescence, Western blot, and extracellular-vesicles analyses. We identified three novel non-invasive biomarkers; all with an increased expression pattern in patients (PCA3: p = 0.002, S100A4: p ≤ 0.0001 and MRC2: p = 0.005). S100A4 presents the most informative AUC (area under the curve) (0.735). Combination of S100A4, MRC2, and PCA3 increases the discriminatory power between patients and controls and between different more and less aggressive stages (AUC = 0.761, p ≤ 0.0001). However, although a sensitivity of 97.47% in PCA3 and a specificity of 90.32% in S100A4 was reached, the detection signal level could be variable in some analyses owing to tumor heterogeneity. This is the first time that the role of S100A4 and MRC2 has been described in PC aggressiveness. Moreover, the combination of S100A4, MRC2, and PCA3 has never been described as a non-invasive biomarker for PC screening and aggressiveness. Full article

(This article belongs to the Special Issue Advances in Agressive Prostate Cancer)

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22 pages, 4458 KiB

Open AccessArticle

Salvage Chemotherapy with Cisplatin, Ifosfamide, and Paclitaxel in Aggressive Variant of Metastatic Castration-Resistant Prostate Cancer

by Gunhild von Amsberg, Mirjam Zilles, Wael Mansour, Philipp Gild, Winfried Alsdorf, Moritz Kaune, Lukas Böckelmann, Jessica Hauschild, Christoph Krisp, Tina Rohlfing, Ceren Saygi, Malik Alawi, Alexandra Zielinski, Claudia Langebrake, Su Jung Oh-Hohenhorst, Sven Perner, Derya Tilki, Hartmut Schlüter, Markus Graefen, Sergey A. Dyshlovoy and Carsten Bokemeyer Show full author list Hide full author list

Int. J. Mol. Sci. 2022, 23(23), 14948; https://doi.org/10.3390/ijms232314948 - 29 Nov 2022

Cited by 2 | Viewed by 2144

Abstract

Significant progress has been achieved in the treatment of metastatic castration-resistant prostate cancer (mCRPC). However, results in patients with aggressive variant prostate cancer (AVPC) have been disappointing. Here, we report retrospectively collected data from intensively pretreated AVPC patients (n = 17; 88.2% visceral metastases; 82% elevation of neuroendocrine markers) treated with salvage chemotherapy consisting of cisplatin, ifosfamide, and paclitaxel (TIP). At the interim analysis, 60% of patients showed radiographic response or stable disease (PFS = 2.5 months; OS = 6 months). In men who responded to chemotherapy, an OS > 15 months was observed. Preclinical analyses confirmed the high activity of the TIP regimen, especially in docetaxel-resistant prostate cancer cells. This effect was primarily mediated by increased cisplatin sensitivity in the emergence of taxane resistance. Proteomic and functional analyses identified a lower DNA repair capacity and cell cycle machinery deficiency to be causative. In contrast, paclitaxel showed inconsistent effects, partially antagonizing cisplatin and ifosfamide in some AVPC models. Consequently, paclitaxel has been excluded from the TIP combination for future patients. In summary, we report for the first time the promising efficacy of TIP as salvage therapy in AVPC. Our preclinical data indicate a pivotal role for cisplatin in overcoming docetaxel resistance. Full article

(This article belongs to the Special Issue Advances in Agressive Prostate Cancer)

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16 pages, 2838 KiB

Open AccessArticle

The Association between Cyclin Dependent Kinase 2 Associated Protein 1 (CDK2AP1) and Molecular Subtypes of Lethal Prostate Cancer

by Yaser Gamallat, Andrea Bakker, Ealia Khosh Kish, Muhammad Choudhry, Simon Walker, Saood Aldakheel, Sima Seyedi, Kuo-Cheng Huang, Sunita Ghosh, Geoffrey Gotto and Tarek A. Bismar

Int. J. Mol. Sci. 2022, 23(21), 13326; https://doi.org/10.3390/ijms232113326 - 1 Nov 2022

Cited by 2 | Viewed by 1521

Abstract

Prostate cancer (PCa) is one of the most commonly diagnosed types of malignancy and is the second leading cause of cancer-related death in men in developed countries. Cyclin dependent kinase 2 associate protein 1(CDK2AP1) is an epigenetic and cell cycle regulator gene which has been downregulated in several malignancies, but its involvement in PCa has not yet been investigated in a clinical setting. We assessed the prognostic value of CDK2AP1 expression in a cohort of men diagnosed with PCa (n = 275) treated non-surgically by transurethral resection of the prostate (TURP) and studied the relationship between CDK2AP1 expression to various PCa molecular subtypes (ERG, PTEN, p53 and AR) and evaluated the association with clinical outcome. Further, we used bioinformatic tools to analyze the available TCGA PRAD transcriptomic data to explore the underlying mechanism. Our data confirmed increased expression of CDK2AP1 with higher Gleason Grade Group (GG) and metastatic PCa (p <0.0001). High CDK2AP1 expression was associated with worse overall survival (OS) (HR: 1.62, CI: 1.19–2.21, p = 0.002) and cause-specific survival (CSS) (HR: 2.012, CI 1.29–3.13, p = 0.002) using univariate analysis. When compared to each sub-molecular type. High CDK2AP1/PTEN-loss, abnormal AR or p53 expression showed even worse association to poorer OS and CCS and remained significant when adjusted for GG. Our data indicates that CDK2AP1 directly binds to p53 using the Co-Immunoprecipitation (Co-IP) technique, which was validated using molecular docking tools. This suggests that these two proteins have a significant association through several binding features and correlates with our observed clinical data. In conclusion, our results indicated that the CDK2AP1 overexpression is associate with worse OS and CSS when combined with certain PCa molecular subtypes; interaction between p53 stands out as the most prominent candidate which directly interacts with CDK2AP1. Full article

(This article belongs to the Special Issue Advances in Agressive Prostate Cancer)

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16 pages, 1543 KiB

Open AccessArticle

ALDH3A2, ODF2, QSOX2, and MicroRNA-503-5p Expression to Forecast Recurrence in TMPRSS2-ERG-Positive Prostate Cancer

by Anastasiya A. Kobelyatskaya, Alexander A. Kudryavtsev, Anna V. Kudryavtseva, Anastasiya V. Snezhkina, Maria S. Fedorova, Dmitry V. Kalinin, Vladislav S. Pavlov, Zulfiya G. Guvatova, Pavel A. Naberezhnev, Kirill M. Nyushko, Boris Y. Alekseev, George S. Krasnov, Elizaveta V. Bulavkina and Elena A. Pudova

Int. J. Mol. Sci. 2022, 23(19), 11695; https://doi.org/10.3390/ijms231911695 - 2 Oct 2022

Cited by 3 | Viewed by 1910

Abstract

Following radical surgery, patients may suffer a relapse. It is important to identify such patients so that therapy tactics can be modified appropriately. Existing stratification schemes do not display the probability of recurrence with enough precision since locally advanced prostate cancer (PCa) is classified as high-risk but is not ranked in greater detail. Between 40 and 50% of PCa cases belong to the TMPRSS2-ERG subtype that is a sufficiently homogeneous group for high-precision prognostic marker search to be possible. This study includes two independent cohorts and is based on high throughput sequencing and qPCR data. As a result, we have been able to suggest a perspective-trained model involving a deep neural network based on both qPCR data for mRNA and miRNA and clinicopathological criteria that can be used for recurrence risk forecasts in patients with TMPRSS2-ERG-positive, locally advanced PCa (the model uses ALDH3A2 + ODF2 + QSOX2 + hsa-miR-503-5p + ISUP + pT, with an AUC = 0.944). In addition to the prognostic model’s use of identified differentially expressed genes and miRNAs, miRNA–target pairs were found that correlate with the prognosis and can be presented as an interactome network. Full article

(This article belongs to the Special Issue Advances in Agressive Prostate Cancer)

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Review

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20 pages, 851 KiB

Open AccessReview

Complexities of Prostate Cancer

by Sobia Wasim, Sang-Yoon Lee and Jaehong Kim

Int. J. Mol. Sci. 2022, 23(22), 14257; https://doi.org/10.3390/ijms232214257 - 17 Nov 2022

Cited by 29 | Viewed by 6728

Abstract

Prostate cancer has a long disease history and a wide variety and uncertainty in individual patients’ clinical progress. In recent years, we have seen a revolutionary advance in both prostate cancer patient care and in the research field. The power of deep sequencing has provided cistromic and transcriptomic knowledge of prostate cancer that has not discovered before. Our understanding of prostate cancer biology, from bedside and molecular imaging techniques, has also been greatly advanced. It is important that our current theragnostic schemes, including our diagnostic modalities, therapeutic responses, and the drugs available to target non-AR signaling should be improved. This review article discusses the current progress in the understanding of prostate cancer biology and the recent advances in diagnostic and therapeutic strategies. Full article

(This article belongs to the Special Issue Advances in Agressive Prostate Cancer)

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