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Biology Direct Jun 2024Prostate cancer (PCa) is the second leading cause of tumor-related mortality in men. Metastasis from advanced tumors is the primary cause of death among patients....
BACKGROUND
Prostate cancer (PCa) is the second leading cause of tumor-related mortality in men. Metastasis from advanced tumors is the primary cause of death among patients. Identifying novel and effective biomarkers is essential for understanding the mechanisms of metastasis in PCa patients and developing successful interventions.
METHODS
Using the GSE8511 and GSE27616 data sets, 21 metastasis-related genes were identified through the weighted gene co-expression network analysis (WGCNA) method. Subsequent functional analysis of these genes was conducted on the gene set cancer analysis (GSCA) website. Cluster analysis was utilized to explore the relationship between these genes, immune infiltration in PCa, and the efficacy of targeted drug IC50 scores. Machine learning algorithms were then employed to construct diagnostic and prognostic models, assessing their predictive accuracy. Additionally, multivariate COX regression analysis highlighted the significant role of POLD1 and examined its association with DNA methylation. Finally, molecular docking and immunohistochemistry experiments were carried out to assess the binding affinity of POLD1 to PCa drugs and its impact on PCa prognosis.
RESULTS
The study identified 21 metastasis-related genes using the WGCNA method, which were found to be associated with DNA damage, hormone AR activation, and inhibition of the RTK pathway. Cluster analysis confirmed a significant correlation between these genes and PCa metastasis, particularly in the context of immunotherapy and targeted therapy drugs. A diagnostic model combining multiple machine learning algorithms showed strong predictive capabilities for PCa diagnosis, while a transfer model using the LASSO algorithm also yielded promising results. POLD1 emerged as a key prognostic gene among the metastatic genes, showing associations with DNA methylation. Molecular docking experiments supported its high affinity with PCa-targeted drugs. Immunohistochemistry experiments further validated that increased POLD1 expression is linked to poor prognosis in PCa patients.
CONCLUSIONS
The developed diagnostic and metastasis models provide substantial value for patients with prostate cancer. The discovery of POLD1 as a novel biomarker related to prostate cancer metastasis offers a promising avenue for enhancing treatment of prostate cancer metastasis.
PubMed: 38918844
DOI: 10.1186/s13062-024-00494-x -
Clinical Proteomics Jun 2024Tumorigenesis and progression of prostate cancer (PCa) are indispensably dependent on androgen receptor (AR). Antiandrogen treatment is the principal preference for...
BACKGROUND
Tumorigenesis and progression of prostate cancer (PCa) are indispensably dependent on androgen receptor (AR). Antiandrogen treatment is the principal preference for patients with advanced PCa. However, the molecular characteristics of PCa with antiandrogen intervention have not yet been fully uncovered.
METHODS
We first performed proteome analysis with 32 PCa tumor samples and 10 adjacent tissues using data-independent acquisition (DIA)- parallel accumulation serial fragmentation (PASEF) proteomics. Then label-free quantification (LFQ) mass spectrometry was employed to analyze protein profiles in LNCaP and PC3 cells.
RESULTS
M-type creatine kinase CKM and cartilage oligomeric matrix protein COMP were demonstrated to have the potential to be diagnostic biomarkers for PCa at both mRNA and protein levels. Several E3 ubiquitin ligases and deubiquitinating enzymes (DUBs) were significantly altered in PCa and PCa cells under enzalutamide treatment, and these proteins might reprogram proteostasis at protein levels in PCa. Finally, we discovered 127 significantly varied proteins in PCa samples with antiandrogen therapy and further uncovered 4 proteins in LNCaP cells upon enzalutamide treatment.
CONCLUSIONS
Our research reveals new potential diagnostic biomarkers for prostate cancer and might help resensitize resistance to antiandrogen therapy.
PubMed: 38918720
DOI: 10.1186/s12014-024-09490-9 -
Asian Pacific Journal of Cancer... Jun 2024Indian population is aging and the cancer rates are rising. Older adults (OAs)(≥60 years) with cancer require specialized care. However, data on geriatric cancer...
INTRODUCTION
Indian population is aging and the cancer rates are rising. Older adults (OAs)(≥60 years) with cancer require specialized care. However, data on geriatric cancer epidemiology is scarce.
METHODS
The study compiled the geriatric cancer data from the published reports(2012-2014) of Indian population-based cancer registries(PBCRs).
RESULTS
Of the 1,61,363 cancers registered in the Indian PBCRs, 72,446(44.9%) occur in OAs, with 21,805(30.1%), 18,349(25.3%), 14,645(20.2%), and 17,647(24.4%) occurring in 60-64, 65-69, 70-74, and ≥75year age groups. The truncated incidence rates for OAs are 555.9,404.5, and 481.9 for males, females, and OA populations respectively. The common cancers are lung, prostate, and esophagus cancers in males, breast, cervix, and lung in females. The overall common cancers are lung, prostate, and breast. While >50% of the incident cases of prostate, and bladder cancers occurred in OAs, <20% of Hodgkin lymphoma and thyroid cancers occurred in OAs. OA cancer epidemiology has a regional variation, highest in South India and lowest in Western India.
CONCLUSION
The current study quantifies the cancer burden in the Indian geriatric population. Understanding the epidemiology of geriatric cancers is vital to health program planning and implementation. Increased awareness, focused resource allocation, research, and national policies for streamlining care will all help to improve geriatric cancer outcomes.
PubMed: 38918663
DOI: 10.31557/APJCP.2024.25.6.2011 -
Asian Pacific Journal of Cancer... Jun 2024With earlier prostate cancer (PCa) diagnosis and increased survivorship, post-treatment quality of life (QoL) has become increasingly important. The Expanded Prostate...
BACKGROUND
With earlier prostate cancer (PCa) diagnosis and increased survivorship, post-treatment quality of life (QoL) has become increasingly important. The Expanded Prostate Cancer Index Composite (EPIC) is a widely adopted QoL instrument for PCa. We aimed to create a Punjabi version of EPIC to further research in the Punjabi-speaking population.
METHODS
A prototype of the Punjabi version of EPIC was created by forward-backward translations and revision. After concluding the cultural adaptation phase by interviewing 15 participants, a pilot version was created. Validation of the pilot version was performed by having 72 participants complete the Punjabi EPIC and another commonly used QoL instrument, the EORTC QLQ-c30, twice within a 4-week period. Test retest reliability (Pearson's correlations and difference distribution) and internal consistency (Cronbach's alpha) were measured using SAS version 9.4.
RESULTS
Modifications were needed for the prototype Punjabi version after forward-backward translations. Cultural adaptation has highlighted a few issues including syntax and terminology. Test-retest reliability of the Urinary, Bowel, Sexual and Hormone domains were 0.88, 0.91, 0.91, and 0.95, respectively, and subscale correlations ranged from 0.75 to 0.93. Internal consistency for domains and subscales was good except for Sexual Domain. Performance of EPIC is comparable, and in some cases, slightly better than validated Punjabi version of EORTC QLQ-C30.
CONCLUSIONS
The EPIC questionnaire was successfully translated into Punjabi and was culturally adapted. The resultant Punjabi version has high reliability and validity and will be an important tool for QoL research in the Punjabi population. EPIC was successfully translated, culturally adapted, and validated with high reliability and validity into Punjabi. It will be a valuable QoL tool for physicians in clinical and research settings, and for patients in decision-making.
PubMed: 38918655
DOI: 10.31557/APJCP.2024.25.6.1945 -
Asian Pacific Journal of Cancer... Jun 2024There have been several reports on rechallenge with docetaxel, cabazitaxel, abiraterone acetate, or ethinylestradiol for metastatic castration-resistant prostate cancer...
OBJECTIVE
There have been several reports on rechallenge with docetaxel, cabazitaxel, abiraterone acetate, or ethinylestradiol for metastatic castration-resistant prostate cancer (mCRPC). However, the efficacy of enzalutamide rechallenge for mCRPC has not been evaluated.
METHODS
We retrospectively reviewed 63 consecutive patients who received enzalutamide for mCRPC at our institution between 2014 and 2022. Eight of these patients underwent rechallenge with enzalutamide after disease progression on prior enzalutamide and other therapy and were the focus of this study. The prostate-specific antigen (PSA) response (PSA decrease >50%), PSA progression-free survival, treatment duration, overall survival (OS) after CRPC, and treatment-related adverse events were evaluated.
RESULTS
PSA decline to enzalutamide rechallenge was observed in 6 patients (75%), of which 2 patients had a PSA response. The median treatment duration was 4 months (range 1-12) and median PSA progression-free survival was 3 months (range 1-7). Median OS after CRPC was 41 months. OS after CRPC was not increased in patients with a PSA response. No toxicities were worse than grade ≥3.
CONCLUSION
Enzalutamide rechallenge achieved a PSA response in a quarter of our patients with mCRPC after disease progression on prior enzalutamide. However, no improvement of OS was identified in these patients.
Topics: Humans; Male; Prostatic Neoplasms, Castration-Resistant; Phenylthiohydantoin; Nitriles; Benzamides; Retrospective Studies; Aged; Middle Aged; Prostate-Specific Antigen; Follow-Up Studies; Survival Rate; Prognosis; Aged, 80 and over; Antineoplastic Agents
PubMed: 38918645
DOI: 10.31557/APJCP.2024.25.6.1863 -
Prostate Cancer and Prostatic Diseases Jun 2024Sexual difficulties are a recognized consequence of prostate cancer (PCa) treatments. An estimated one in three men who have sex with men (MSM) receive PCa a diagnosis... (Review)
Review
BACKGROUND
Sexual difficulties are a recognized consequence of prostate cancer (PCa) treatments. An estimated one in three men who have sex with men (MSM) receive PCa a diagnosis during their lifetime. MSM may experience all types of sexual dysfunction as reported in men who have sex with women (MSW), along with a number of more specific bothersome problems. This systematic literature review aims to evaluate sexual outcomes in MSM who have undergone radical prostatectomy (RP).
METHODS
A systematic review was carried out following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. The searches were made using relevant keywords in the PubMed, Scopus, and Web of Science databases, thus including the whole literature from January 2000 to November 2023. Studies which did not allow to retrieve data on sexual outcomes on MSM treated with RP for PCa were excluded. Data on sexual outcomes and health-related quality of life (HRQoL) were retrieved, mostly including changes in libido, erectile function, ejaculatory disorders, orgasm, climacturia, changes in role-in-sex identity, changes in sexual partnerships, and the presence of painful receptive anal intercourses (AI).
PROSPERO ID
CRD42024502592.
RESULTS
Six articles met the inclusion criteria. In total, data of 260 patients were analyzed. Three main themes emerged: (a) MSM may experience specific sexual dysfunctions due to the different dynamics of their intimacy; (b) the lack of tool validated on gay and bisexual population to assess sexual outcomes (c) the need for a tailored approach that also takes into account sexual orientation throughout the oncological journey.
CONCLUSIONS
MSM undergoing RP may experience similar sexual problems as MSW. Painful AI should be considered a potential post-operative adverse outcome in MSM. Future studies should prioritize validating a questionnaire that explores AI. Healthcare providers should adopt a tailored approach that takes into account sexual orientation throughout the cancer journey.
PubMed: 38918583
DOI: 10.1038/s41391-024-00861-9 -
La Radiologia Medica Jun 2024Radical prostatectomy (RP) is recommended in case of localized or locally advanced prostate cancer (PCa), but it can lead to side effects, including urinary incontinence... (Review)
Review
BACKGROUND
Radical prostatectomy (RP) is recommended in case of localized or locally advanced prostate cancer (PCa), but it can lead to side effects, including urinary incontinence (UI) and erectile dysfunction (ED). Magnetic resonance imaging (MRI) is recommended for PCa diagnosis and staging, but it can also improve preoperative risk-stratification.
PURPOSE
This nonsystematic review aims to provide an overview on factors involved in RP side effects, highlighting anatomical and pathological aspects that could be included in a structured report.
EVIDENCE SYNTHESIS
Considering UI evaluation, MR can investigate membranous urethra length (MUL), prostate volume, the urethral sphincter complex, and the presence of prostate median lobe. Longer MUL measurement based on MRI is linked to a higher likelihood of achieving continence restoration. For ED assessment, MRI and diffusion tensor imaging identify the neurovascular bundle and they can aid in surgery planning. Finally, MRI can precisely describe extra-prostatic extension, prostate apex characteristics and lymph-node involvement, providing valuable preoperative information for PCa treatment.
CONCLUSIONS
Anatomical principals structures involved in RP side effects can be assessed with MR. A standardized MR report detailing these structures could assist urologists in planning optimal and tailored surgical techniques, reducing complications, and improving patients' care.
PubMed: 38918291
DOI: 10.1007/s11547-024-01831-w -
International Journal of Behavioral... Jun 2024Social relationships are important health resources and may be investigated as social networks. We measured cancer patients' social subnetworks divided into generic...
BACKGROUND
Social relationships are important health resources and may be investigated as social networks. We measured cancer patients' social subnetworks divided into generic social networks (people known to the patients) and disease-specific social networks (the persons talked to about the cancer) during 3 years after diagnosis.
METHOD
Newly diagnosed patients with localized breast cancer (n = 222), lymphoma (n = 102), and prostate cancer (n = 141) completed a questionnaire on their social subnetworks at 2-5 months after diagnosis and 9, 18, and 36 months thereafter. Generic and cancer-specific numbers of persons of spouse/partner; other family; close relatives, in detail; and friends were recorded as well as cancer-specific numbers of persons in acquaintances; others with cancer; work community; healthcare professionals; and religious, hobby, and civic participation. The data was analyzed with regression models.
RESULTS
At study entry, most patients had a spouse/partner, all had close relatives (the younger, more often parents; and the older, more often adult children with families) and most also friends. The cancer was typically discussed with them, and often with acquaintances and other patients (74-86%). Only minor usually decreasing time trends were seen. However, the numbers of distant relatives and friends were found to strongly increase by the 9-month evaluation (P < 0.001).
CONCLUSION
Cancer patients have multiple social relationships and usually talk to them about their cancer soon after diagnosis. Most temporal changes are due to the natural course of life cycle. The cancer widened the patients' social networks by including other patients and healthcare professionals and by an increased number of relatives and friends.
PubMed: 38918279
DOI: 10.1007/s12529-024-10292-4 -
Aktuelle Urologie Jun 2024Prostate cancer is one of the most common cancers in men in Europe. Several classes of agents can be considered for the treatment of metastatic prostate carcinoma, and...
BACKGROUND
Prostate cancer is one of the most common cancers in men in Europe. Several classes of agents can be considered for the treatment of metastatic prostate carcinoma, and their use is supported by extensive guidelines. In the treatment of metastatic castration-resistant prostate cancer (mCRPC), it is currently unclear which sequence of systemic therapies is most effective. Currently approved system therapies in the castration-resistant setting generally include hormone-manipulating agents, taxane-based chemotherapies, radioactive agents, or inhibitiors of DNA repair mechanisms. This study aims to summarize real world data of mCRPC therapy.
METHODS
Retrospectively, 90 mCRPC patients undergoing treatment at the University Hospital Schleswig-Holstein, Lübeck Campus between February 2006 and March 2020 were identified. The patient data were analyzed for their treatment sequence and disease progression. Due to the inclusion period, the mCRPC therapy sequences studied were limited to: Abiraterone, Cabazitaxel, Docetaxel, Enzalutamide, Lutetium-177-PSMA and Radium-223. The analysis includes the therapy sequences and their duration, clinical information of the respective cohort, overall and cancer-specific survival (OS/CSS) as well as time to second-line therapy in relation to the respective first-line therapy.
RESULTS
Approximately two-thirds of patients underwent a true therapy sequence (at least two of the drugs listed above), with this proportion halving by the third line.The majority of patients received the sequence (first/second line) abiraterone/docetaxel (n=13), followed by docetaxel/abiraterone (n=12) and abiraterone/enzalutamid (n=10) and docetaxel/docetaxel (n=8).Within the different docetaxel sequences, first-line (mean 4.7 months ± SD 3.1; median 4.0) and rechallenge (mean 5.3 months ± SD 5.9; median 3.0) therapy durations were the longest. The subjective side effect rate of docetaxel was lower in the second line, so that a better tolerability can be assumed here.The abiraterone/docetaxel sequence was used mainly in patients with metachronous metastases. Among the different sequences of abiraterone, first-line (mean 10.8 months ± SD 10.2; median 9.0) and second-line (mean 10.6 months ± SD 9.0; median 7.0) therapy durations were the longest.The sequence abiraterone/enzalutamide was prescribed mainly to older patients with synchronous metastases. Among the different enzalutamide sequences first-line (mean 9.6 months ± SD 7.1; median 7.0) and rechallenge (mean 11.0 ± SD 0.0; median 11.0) therapy durations were the longest.In contrast, the sequence docetaxel/docetaxel was used mainly in younger patients with a high initial PSA.The evaluation shows a trend that both abiraterone and enzalutamide can account for a survival advantage in the first line.
CONCLUSION
Ultimately, an optimal treatment sequence cannot be confidently derived from these data.However, it was found that only a small proportion of patients underwent fourth- or even fifth-line treatment at all. Thus, the focus on first- and second-line in this study seems reasonable. It could be shown in a trend that docetaxel as first-line therapy seems to be disadvantegous regarding OS as well as CSS when compared to abiraterone or enzalutamide. However, due to the small number of patients in this study, a clear significance cannot be derived. Moreover, the subjectively better tolerability of docetaxel in the second-line setting could provide an impetus for treatment planning in multimorbid elderly patients in the future. The sequence abiraterone/docetaxel may offer a beneficial option for initial mCRPC therapy.
PubMed: 38917849
DOI: 10.1055/a-2295-8720 -
Clinical Genitourinary Cancer Jun 2024Prostate cancer (PCa) located in the peripheral zone (PZ) and transitional zone (TZ) showed a different clinical and pathological characteristic. This passage aims to...
INTRODUCTION
Prostate cancer (PCa) located in the peripheral zone (PZ) and transitional zone (TZ) showed a different clinical and pathological characteristic. This passage aims to preliminarily evaluate the relationship between the zonal heterogeneity of PCa quantitatively assessed by bpMRI and pathological risk stratification of the primary lesion.
METHODS
This prospective study was conducted from January 2019 to February 2023. A total of 113 PCa patients whose bpMRI data indicated that the lesions located in only 1 single zone of the prostate were selected. A transrectal ultrasound and MRI-targeted biopsy were performed to verify the bpMRI results, and then radical prostatectomy (RP) was performed in 3 weeks after the biopsy. The high-risk (HR) group was defined as ISUP grades ≥ 3. Binary regression was performed to evaluate if the zonal heterogeneity could be an independent predictor of the HR group. The receiver operator characteristic (ROC) curve was performed to analyze the added value of zonal location in predicting the HR group.
RESULTS
PSA, T staging, and ISUP grades, incidence of positive surgical margins were significantly lower in the TZ PCa, and the ADCmin, and ADCmean values in the TZ PCa were significantly higher (all P < .01). The zonal heterogeneity could independently predict the HR group patients (OR: 5.170 [1.663-16.067], P = .005) and improve the predicting efficiency of HR patients (AUC 0.824, 95% CI, 0.741-0.889).
CONCLUSIONS
BpMRI could quantitively assess the zonal heterogeneity of PCa precisely and increase the predicting efficacy of HR patients, which can provide better help for clinical individualized treatment.
PubMed: 38917763
DOI: 10.1016/j.clgc.2024.102135