-
Cells Jun 2024Special AT-rich sequence binding protein-2 (SATB2) is a nuclear matrix protein that binds to nuclear attachment regions and is involved in chromatin remodeling and...
Special AT-rich sequence binding protein-2 (SATB2) is a nuclear matrix protein that binds to nuclear attachment regions and is involved in chromatin remodeling and transcription regulation. In stem cells, it regulates the expression of genes required for maintaining pluripotency and self-renewal and epithelial-mesenchymal transition (EMT). In this study, we examined the oncogenic role of SATB2 in prostate cancer and assessed whether overexpression of SATB2 in human normal prostate epithelial cells (PrECs) induces properties of cancer stem cells (CSCs). The results demonstrate that SATB2 is highly expressed in prostate cancer cell lines and CSCs, but not in PrECs. Overexpression of SATB2 in PrECs induces cellular transformation which was evident by the formation of colonies in soft agar and spheroids in suspension. Overexpression of SATB2 in PrECs also resulted in induction of stem cell markers (CD44 and CD133), pluripotency-maintaining transcription factors (cMYC, OCT4, SOX2, KLF4, and NANOG), CADHERIN switch, and EMT-related transcription factors. Chromatin immunoprecipitation assay demonstrated that SATB2 can directly bind to promoters of BCL-2, BSP, NANOG, MYC, XIAP, KLF4, and HOXA2, suggesting SATB2 is capable of directly regulating pluripotency/self-renewal, cell survival, and proliferation. Since prostate CSCs play a crucial role in cancer initiation, progression, and metastasis, we also examined the effects of SATB2 knockdown on stemness. SATB2 knockdown in prostate CSCs inhibited spheroid formation, cell viability, colony formation, cell motility, migration, and invasion compared to their scrambled control groups. SATB2 knockdown in CSCs also upregulated the expression of E-CADHERIN and inhibited the expression of N-CADHERIN, SNAIL, SLUG, and ZEB1. The expression of SATB2 was significantly higher in prostate adenocarcinoma compared to normal tissues. Overall, our data suggest that SATB2 acts as an oncogenic factor where it is capable of inducing malignant changes in PrECs by inducing CSC characteristics.
Topics: Humans; Male; Epithelial-Mesenchymal Transition; Prostatic Neoplasms; Kruppel-Like Factor 4; Matrix Attachment Region Binding Proteins; Transcription Factors; Cell Line, Tumor; Neoplastic Stem Cells; Gene Expression Regulation, Neoplastic; Cell Self Renewal; Cell Proliferation
PubMed: 38891096
DOI: 10.3390/cells13110962 -
BMC Cancer Jun 2024Tumor hypoxia is associated with prostate cancer (PCa) treatment resistance and poor prognosis. Pimonidazole (PIMO) is an investigational hypoxia probe used in clinical...
BACKGROUND
Tumor hypoxia is associated with prostate cancer (PCa) treatment resistance and poor prognosis. Pimonidazole (PIMO) is an investigational hypoxia probe used in clinical trials. A better understanding of the clinical significance and molecular alterations underpinning PIMO-labeled tumor hypoxia is needed for future clinical application. Here, we investigated the clinical significance and molecular alterations underpinning PIMO-labeled tumor hypoxia in patients with localized PCa, in order to apply PIMO as a prognostic tool and to identify potential biomarkers for future clinical translation.
METHODS
A total of 39 patients with localized PCa were recruited and administered oral PIMO before undergoing radical prostatectomy (RadP). Immunohistochemical staining for PIMO was performed on 37 prostatectomy specimens with staining patterns evaluated and clinical association analyzed. Whole genome bisulfite sequencing was performed using laser-capture of microdissected specimen sections comparing PIMO positive and negative tumor areas. A hypoxia related methylation molecular signature was generated by integrating the differentially methylated regions with previously established RNA-seq datasets.
RESULTS
Three PIMO staining patterns were distinguished: diffuse, focal, and comedo-like. The comedo-like staining pattern was more commonly associated with adverse pathology. PIMO-defined hypoxia intensity was positively correlated with advanced pathologic stage, tumor invasion, and cribriform and intraductal carcinoma morphology. The generated DNA methylation signature was found to be a robust hypoxia biomarker, which could risk-stratify PCa patients across multiple clinical datasets, as well as be applicable in other cancer types.
CONCLUSIONS
Oral PIMO unveiled clinicopathologic features of disease aggressiveness in localized PCa. The generated DNA methylation signature is a novel and robust hypoxia biomarker that has the potential for future clinical translation.
Topics: Humans; Male; Prostatic Neoplasms; Aged; Middle Aged; Epigenesis, Genetic; Prostatectomy; DNA Methylation; Nitroimidazoles; Tumor Hypoxia; Biomarkers, Tumor; Prognosis; Administration, Oral
PubMed: 38890593
DOI: 10.1186/s12885-024-12505-1 -
JMIR Research Protocols Jun 2024Receiving a diagnosis of cancer is a profound and often very stressful experience. Few studies have prospectively recruited patients prior to receiving a new diagnosis... (Observational Study)
Observational Study
Quality of Life in Patients and Their Spouses and Cohabitating Partners in the Year Following a Cancer Biopsy (the Couples Cope Study): Protocol for a Prospective Observational Study.
BACKGROUND
Receiving a diagnosis of cancer is a profound and often very stressful experience. Few studies have prospectively recruited patients prior to receiving a new diagnosis of cancer and included spouses or partners.
OBJECTIVE
The aim of the Couples Cope Study is to understand the impact of undergoing a diagnostic biopsy and receiving a new cancer diagnosis on quality of life (QoL) in both patients and their spouses or partners, as well as on the quality of their relationship. This protocol paper describes the study design and assesses the feasibility of recruitment and retention.
METHODS
Study staff reviewed the schedules of collaborating physicians using specific encounter codes to identify patients scheduled for breast or prostate biopsies. Potential participants were prescreened via the electronic health record and sent a recruitment letter at least 2 to 3 weeks prior to their biopsy procedure. Patients subsequently underwent a phone screening to determine eligibility. Patients who enrolled provided study staff with contact information for their spouses or partners. All consent forms were completed online. Surveys were completed online prior to receiving the biopsy results (baseline), and at 1, 3, 6, and 9 months after the biopsy. Study staff engaged in ongoing, personalized contact with participants and sent assessment completion reminders via phone and email.
RESULTS
A total of 2294 patients undergoing a breast or prostate biopsy were identified and 69% (n=1582) were eligible for phone screening following electronic health record prescreening. Of the 431 patients who underwent phone screening, 75% (n=321) were eligible to participate. Of the eligible patients, 72% (n=231) enrolled and 82% (n=190) of enrolled patients had an accompanying partner or spouse who also enrolled. A total of 77% (34/44) of patients who received a cancer diagnosis and 72% (26/36) of their spouses or partners were retained through 9 months, while 80% (53/66) of patients who received a benign diagnosis and 68% (42/62) of their partners were retained.
CONCLUSIONS
Prospective recruitment of patients undergoing diagnostic biopsy and their partners is feasible and requires both strategic collaboration with providers and concerted prescreening and recruitment efforts by study staff. Importantly, this study was able to conduct all study activities online without disrupting clinical workflow and without requiring patients and their spouses or partners to come into the laboratory. Consideration should be given to the ratio of biopsies to cancer diagnoses, which can vary significantly by cancer type. Prospective studies are needed and can inform our ability to provide effective support earlier to couples facing a possible cancer diagnosis. Future studies should examine other tumor types that have received less attention in QoL studies, include behavioral and neurobiological assessments beyond self-report measures, and follow couples beyond 9 months in order to examine long-term effects on QoL.
INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID)
DERR1-10.2196/52361.
Topics: Humans; Spouses; Prospective Studies; Male; Quality of Life; Female; Biopsy; Breast Neoplasms; Prostatic Neoplasms; Middle Aged; Adult; Neoplasms; Aged
PubMed: 38889402
DOI: 10.2196/52361 -
World Journal of Urology Jun 2024Indwelling catheterization following radical prostatectomy is used to aid healing and urinary drainage. While early removal is well investigated, prolonged...
BACKGROUND
Indwelling catheterization following radical prostatectomy is used to aid healing and urinary drainage. While early removal is well investigated, prolonged catheterization has only been investigated in terms of urinary incontinence. Other complications such as anastomotic strictures are unexplored so far. This study aims to analyze the sequelae of catheterization lasting more than 14 days after robotic-assisted radical prostatectomy (RARP).
METHODS
A prospective database of 3087 patients undergoing RARP was analyzed, focusing on 180 patients with catheterization exceeding 14 days (Group A) and 88 matched controls (Group B). Outcome measures included subsequent surgeries, complications, and functional outcomes.
RESULTS
Prolonged catheterization did not significantly increase the need for subsequent surgeries (6% in Group A vs. 7% in Group B, p = .95). However, anastomotic strictures were more common in Group A (3%) compared to Group B (0%) after exclusion of risk factors. Incontinence rates were similar between groups, although a subgroup analysis revealed higher incontinence rates in patients with catheterization exceeding 28 days. No significant differences were observed in erectile function or quality of life between the groups.
CONCLUSION
Prolonged catheterization after RARP does not independently increase the risk of anastomotic strictures in the general population. However, in patients without risk factors, prolonged catheter dwell time may elevate the risk of strictures and subsequent surgeries. Additionally, patients with catheterization exceeding 28 days may experience higher rates of long-term incontinence. Further studies with larger sample sizes are needed to confirm these findings and elucidate the long-term implications of prolonged catheterization.
Topics: Humans; Male; Middle Aged; Prostatectomy; Catheters, Indwelling; Time Factors; Aged; Postoperative Complications; Robotic Surgical Procedures; Urinary Catheterization; Prostatic Neoplasms; Follow-Up Studies; Prospective Studies
PubMed: 38888747
DOI: 10.1007/s00345-024-05080-4 -
Supportive Care in Cancer : Official... Jun 2024Cancer survival is improving, making optimal management of long-term treatment-related adverse effects increasingly important. Exercise and a healthy diet are beneficial...
PURPOSE
Cancer survival is improving, making optimal management of long-term treatment-related adverse effects increasingly important. Exercise and a healthy diet are beneficial and regularly recommended in cancer survivorship guidelines; however, few cancer survivors meet these recommendations so there is a need to explore why. This study aimed to understand experiences receiving exercise and diet support among Australian breast and prostate cancer survivors during and following treatment, and to explore what support they would like to receive.
METHODS
Adults who completed active treatment for breast or prostate cancer were recruited via a private cancer care centre. Using a qualitative descriptive study design, participants attended in-person focus groups that were recorded, transcribed, then analysed using reflexive thematic analysis.
RESULTS
In total, 26 cancer survivors (15 breast, 11 prostate) participated in one of seven focus groups (4 breast, 3 prostate). Two themes were developed: 1) It was just brushed over, and 2) Wanting more. Theme 1 reports that exercise, and especially diet, were rarely discussed. If they were, it was often limited to general recommendations. Theme 2 shows that participants wanted more specific and personalised support, and information about how exercise and/or diet could benefit their cancer treatment.
CONCLUSION
Despite strong interest in receiving personalised exercise and diet support, neither are routinely provided to Western Australian breast and prostate cancer survivors. If support was provided, there was inconsistency in the level and type of support provided. These findings identify important gaps in exercise and diet support provision to cancer survivors and will inform future strategies aiming to improve cancer survivorship care.
Topics: Humans; Prostatic Neoplasms; Male; Cancer Survivors; Focus Groups; Female; Breast Neoplasms; Middle Aged; Aged; Exercise; Qualitative Research; Australia; Adult; Social Support; Diet
PubMed: 38888665
DOI: 10.1007/s00520-024-08652-7 -
World Journal of Urology Jun 2024To assess the patient experience and satisfaction after the implementation in routine of a personalized, digital programme before and after same-day discharge (SDD)...
PURPOSE
To assess the patient experience and satisfaction after the implementation in routine of a personalized, digital programme before and after same-day discharge (SDD) robot-assisted radical prostatectomy (RARP).
METHODS
The study is a pre/post-interventional, multi-surgeon, unicentre, prospective study. All consecutive patients undergoing SDD RARP were included during a 6-month period. After a pre-interventional assessment of the satisfaction rate (n = 26), all patients (n = 46) were introduced to the Betty. Care platform and followed the BETTY COACHING programme which included a specific radical prostatectomy module. The primary endpoint was patient satisfaction 6 weeks after SDD RARP. Secondary endpoints were hospital stay, readmission and complications rates, unplanned visits, and remote monitoring data.
RESULTS
Median age and PSA were 66 years and 7.0 ng/ml. Lymph node-dissection and nerve-sparing procedures were performed in 41.3 and 87.0% of patients, respectively. Median operative time and blood loss were 80 min and 150 ml, respectively. The 90-day rates of unplanned visits, readmission and complications were improved after the digital tool implementation (2.2, 2.2, and 8.7%, respectively). Mean satisfaction score was 9.6 out of 10 (8.0 before implementation). Median duration of pain was 2 days after discharge, with median pain intensity of 2/10. Median duration of daily active use of remote monitoring was 34 days. The urinary continence rate was 91.3% 6 weeks after surgery in the postinterventional cohort.
CONCLUSIONS
The implementation of a personalized, surgery-specific, digital programme combining prehabilitation, patient education, rehabilitation, patient-reported outcome measurement and remote monitoring, improves patient experience and satisfaction and could help promoting early discharge even after a major surgery.
Topics: Humans; Male; Prostatectomy; Patient Satisfaction; Aged; Prospective Studies; Middle Aged; Robotic Surgical Procedures; Prostatic Neoplasms; Patient Discharge; Ambulatory Surgical Procedures; Perioperative Care
PubMed: 38888646
DOI: 10.1007/s00345-024-05099-7 -
Scandinavian Journal of Urology Jun 2024The aim of this study was to evaluate the change in LUTS in patients treated with RALP and to assess factors that may predict an improvement of LUTS.
PROBLEM
The aim of this study was to evaluate the change in LUTS in patients treated with RALP and to assess factors that may predict an improvement of LUTS.
MATERIALS AND METHOD
In our institutional prospective research registry, 1935 patients operated in the period between 2009 and 2021 with complete baseline- and 12-month EPIC-26 questionnaire were eligible for the study. Also SF-12 data estimating general quality of life (QoL) were analyzed. A LUTS summary score was constructed from the two questions concerning voiding stream/residual and frequency, and transformed linearly to a 0-100 scale with higher scores representing less symptoms A change of 6 points or more were considered Meaningful Clinical Differences (MCD). Two summary scores were calculated from the SF-12 - a mental component score (MCS-12) and a physical component score (PCS-12). Multivariate regression was used to estimate covariates associated with postoperative MCD, MCS-12 and PCS-12.
RESULTS
Mean change of LUTS-score showed an increase of 10 points 12-months post-RALP. 52% of patients achieved MCD. In multivariate logistic regression, preoperative LUTS was statistically significant associated with MCD. Reduction of LUTS was associated improved mean score of MCS-12 and PCS-12.
DISCUSSION AND CONCLUSION
Along with information about risk for urinary incontinence after RALP, patients with LUTS at baseline must be informed that these symptoms may be reduced after RALP. In our study, this LUTS reduction was associated with better general QoL.
Topics: Humans; Lower Urinary Tract Symptoms; Male; Prostatectomy; Robotic Surgical Procedures; Middle Aged; Aged; Prostatic Neoplasms; Laparoscopy; Quality of Life; Prospective Studies
PubMed: 38888041
DOI: 10.2340/sju.v59.40070 -
Frontiers in Immunology 2024Myeloid-derived suppressor cell (MDSC) exhibits immunosuppressive functions and affects cancer progression, but its relationship with prostate cancer remains unclear. We...
INTRODUCTION
Myeloid-derived suppressor cell (MDSC) exhibits immunosuppressive functions and affects cancer progression, but its relationship with prostate cancer remains unclear. We elucidated the association of polymorphonuclear MDSC (PMN-MDSC) and monocytic MDSC (M-MDSC) levels of the total peripheral blood mononuclear cells (PBMCs) with prostate cancer progression and evaluated their roles as prognostic indicators.
METHODS
We enrolled 115 patients with non-metastatic hormone-sensitive prostate cancer (nmHSPC, n = 62), metastatic hormone-sensitive prostate cancer (mHSPC, n = 23), and metastatic castration-resistant prostate cancer (mCRPC, n = 30). Subsequently, the proportions of MDSCs in each disease progression were compared. Log-rank tests and multivariate Cox regression analyses were performed to ascertain the associations of overall survival.
RESULTS
The patients with mCRPC had significantly higher PMN-MDSC percentage than those with nmHSPC and mHSPC (P = 7.73 × 10 and 0.0014). Significantly elevated M-MDSC levels were observed in mCRPC patients aged <70 years (P = 0.016) and with a body mass index (BMI) <25 kg/m (P = 0.043). The high PMN-MDSC group had notably shorter median survival duration (159 days) than the low PMN-MDSC group (768 days, log-rank P = 0.018). In the multivariate analysis including age, BMI, and MDSC subset, PMN-MDSC was significantly associated with prognosis (hazard ratios, 3.48; 95% confidence interval: 1.05-11.56, P = 0.042).
DISCUSSION
PMN-MDSC levels are significantly associated with mCRPC prognosis. Additionally, we highlight the remarkable associations of age and BMI with M-MDSC levels in mCRPC, offering novel insights into MDSC dynamics in prostate cancer progression.
Topics: Humans; Male; Myeloid-Derived Suppressor Cells; Prostatic Neoplasms, Castration-Resistant; Aged; Prognosis; Middle Aged; Neutrophils; Disease Progression; Aged, 80 and over; Neoplasm Metastasis
PubMed: 38887300
DOI: 10.3389/fimmu.2024.1372771 -
Frontiers in Immunology 2024The localization, density but mostly the phenotype of tumor infiltrating lymphocytes (TIL) provide important information on the initial interaction between the host...
INTRODUCTION
The localization, density but mostly the phenotype of tumor infiltrating lymphocytes (TIL) provide important information on the initial interaction between the host immune system and the tumor. Our objective was to assess the prognostic significance of T (CD3), T regulatory (T) (FoxP3) and T memory (T) (CD45RO) infiltrating lymphocytes and of genes associated with TIL in prostate cancer (PCa).
METHODS
Immunohistochemistry (IHC) was used to assess the infiltration of CD3, FoxP3 and CD45RO cells in the tumor area, tumor margin and adjacent normal-like epithelium of a series of 98 PCa samples with long clinical follow-up. Expression of a panel of 31 TIL-associated genes was analyzed by Taqman Low-Density Array (TLDA) technology in another series of 50 tumors with long clinical follow-up. Kaplan-Meier and Cox proportional hazards regression analyses were performed to determine association of these markers with biochemical recurrence (BCR), need for definitive androgen deprivation therapy (ADT) or lethal PCa.
RESULTS
TIL subtypes were present at different densities in the tumor, tumor margin and adjacent normal-like epithelium, but their density and phenotype in the tumor area were the most predictive of clinical outcomes. In multivariate analyses, a high density of T (high FoxP3/CD3 cell ratio) predicted a higher risk for need of definitive ADT (HR=7.69, p=0.001) and lethal PCa (HR=4.37, p=0.04). Conversely, a high density of T (high CD45RO/CD3 cell ratio) predicted a reduced risk of lethal PCa (HR=0.06, p=0.04). TLDA analyses showed that a high expression of FoxP3 was associated with a higher risk of lethal PCa (HR=5.26, p=0.02). Expression of CTLA-4, PD-1, TIM-3 and LAG-3 were correlated with that of FoxP3. Amongst these, only a high expression of TIM-3 was associated with a significant higher risk for definitive ADT in univariate Cox regression analysis (HR=3.11, p=0.01).
CONCLUSION
These results show that the proportion of T and T found within the tumor area is a strong and independent predictor of late systemic progression of PCa. Our results also suggest that inhibition of TIM-3 might be a potential approach to counter the immunosuppressive functions of T in order to improve the anti-tumor immune response against PCa.
Topics: Humans; Male; Lymphocytes, Tumor-Infiltrating; Prostatic Neoplasms; T-Lymphocytes, Regulatory; Aged; Prognosis; Middle Aged; Memory T Cells; Forkhead Transcription Factors; Biomarkers, Tumor
PubMed: 38887294
DOI: 10.3389/fimmu.2024.1372837 -
Frontiers in Endocrinology 2024Prostate cancer (PCa) is commonly occurred with high incidence in men worldwide, and many patients will be eventually suffered from the dilemma of castration-resistance... (Review)
Review
Prostate cancer (PCa) is commonly occurred with high incidence in men worldwide, and many patients will be eventually suffered from the dilemma of castration-resistance with the time of disease progression. Castration-resistant PCa (CRPC) is an advanced subtype of PCa with heterogeneous carcinogenesis, resulting in poor prognosis and difficulties in therapy. Currently, disorders in androgen receptor (AR)-related signaling are widely acknowledged as the leading cause of CRPC development, and some non-AR-based strategies are also proposed for CRPC clinical analyses. The initiation of CRPC is a consequence of abnormal interaction and regulation among molecules and pathways at multi-biological levels. In this study, CRPC-associated genes, RNAs, proteins, and metabolites were manually collected and integrated by a comprehensive literature review, and they were functionally classified and compared based on the role during CRPC evolution, i.e., drivers, suppressors, and biomarkers, etc. Finally, translational perspectives for data-driven and artificial intelligence-powered CRPC systems biology analysis were discussed to highlight the significance of novel molecule-based approaches for CRPC precision medicine and holistic healthcare.
Topics: Humans; Prostatic Neoplasms, Castration-Resistant; Male; Precision Medicine; Receptors, Androgen; Biomarkers, Tumor; Prognosis
PubMed: 38887275
DOI: 10.3389/fendo.2024.1360430