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Translational Andrology and Urology May 2024
PubMed: 38855591
DOI: 10.21037/tau-23-674 -
Frontiers in Oncology 2024Urothelial Bladder Cancer (BC) is the ninth most common cancer worldwide. It is classified into Non Muscle Invasive (NMIBC) and Muscle Invasive Bladder Cancer (MIBC),...
INTRODUCTION
Urothelial Bladder Cancer (BC) is the ninth most common cancer worldwide. It is classified into Non Muscle Invasive (NMIBC) and Muscle Invasive Bladder Cancer (MIBC), which are characterized by frequent recurrences and progression rate, respectively. The diagnosis and monitoring are obtained through invasive methods as cystoscopy and post-surgery biopsies. Thus, a panel of biomarkers able to discriminate BC based on grading or staging represents a significant step forward in the patients' workup. In this perspective, long non-coding RNAs (lncRNAs) are emerged as reliable candidates as potential biomarker given their specific and regulated expression. In the present work we propose two lncRNAs, the Small Ubiquitin Modifier 1 pseudogene 3 (SUMO1P3), a poorly characterized pseudogene, and the Urothelial Carcinoma Associated 1 (UCA1) as candidates to monitor the BC progression.
METHODS
This study was a retrospective trial enrolling NMIBC and MIBC patients undergoing surgical intervention: the expression of the lncRNA SUMO1P3 and UCA1 was evaluated in urine from 113 subjects (cases and controls). The receiver operating characteristic curve analysis was used to evaluate the performance of single or combined biomarkers in discriminating cases from controls.
RESULTS
SUMO1P3 and UCA1 expression in urine was able to significantly discriminate low grade NMIBC, healthy control and benign prostatic hyperplasia subjects versus high grade NMIBC and MIBC patients. We also demonstrated that miR-320a, which binds SUMO1P3, was reduced in high grade NMIBC and MIBC patients and the SUMO1P3/miR-320a ratio was used to differentiate cases versus controls, showing a statistically significant power. Finally, we provided an automated method of RNA extraction coupled to ddPCR analysis in a perspective of clinical application.
DISCUSSION
We have shown that the lncRNA SUMO1P3 is increased in urine from patients with high grade NMIBC and MIBC and that it is likely to be good candidate to predict bladder cancer progression if used alone or in combination with UCA1 or with miRNA320a.
PubMed: 38846969
DOI: 10.3389/fonc.2024.1325157 -
Journal of Cancer Immunology 2024The role of the microbiome in the development and treatment of genitourinary malignancies is just starting to be appreciated. Accumulating evidence suggests that the...
INTRODUCTION & OBJECTIVE
The role of the microbiome in the development and treatment of genitourinary malignancies is just starting to be appreciated. Accumulating evidence suggests that the microbiome can modulate immunotherapy through signaling in the highly dynamic tumor microenvironment. Nevertheless, much is still unknown about the immuno-oncology-microbiome axis, especially in urologic oncology. The objective of this review is to synthesize our current understanding of the microbiome's role in modulating and predicting immunotherapy response to genitourinary malignancies.
METHODS
A literature search for peer-reviewed publications about the microbiome and immunotherapy response in bladder, kidney, and prostate cancer was conducted. All research available in PubMed, Google Scholar, clinicaltrials.gov, and bioRxiv up to September 2023 was analyzed.
RESULTS
Significant differences in urinary microbiota composition have been found in patients with genitourinary cancers compared to healthy controls. Lactic acid-producing bacteria, such as and genera, may have value in augmenting BCG responsiveness to bladder cancer. BCG may also be a dynamic regulator of PD-L1. Thus, the combination of BCG and immune checkpoint inhibitors may be an effective strategy for bladder cancer management. In advanced renal cell carcinoma, studies show that recent antibiotic administration negatively impacts survival outcomes in patients undergoing immunotherapy, while administration of CBM588, a live bacterial product, is associated with improved progression-free survival. Specific bacterial taxa, such as , have been linked with response to pembrolizumab in metastatic castrate-resistant prostate cancer. Fecal microbiota transplant has been shown to overcome resistance and reduce toxicity to immunotherapy; it is currently being investigated for both kidney and prostate cancers.
CONCLUSIONS
Although the exact mechanism is unclear, several studies identify a symbiotic relationship between microbiota-centered interventions and immunotherapy efficacy. It is possible to improve immunotherapy responsiveness in genitourinary malignancies using the microbiome, but further research with more standardized methodology is warranted.
PubMed: 38846356
DOI: 10.33696/cancerimmunol.6.078 -
Indian Journal of Dermatology 2024
PubMed: 38841224
DOI: 10.4103/ijd.ijd_919_23 -
Scientific Reports Jun 2024Six Transmembrane Epithelial Antigen of Prostate 2 (STEAP2) belongs to a family of metalloreductases, which indirectly aid in uptake of iron and copper ions. Its role in...
Six Transmembrane Epithelial Antigen of Prostate 2 (STEAP2) belongs to a family of metalloreductases, which indirectly aid in uptake of iron and copper ions. Its role in hepatocellular carcinoma (HCC) remains to be characterized. Here, we report that STEAP2 expression was upregulated in HCC tumors compared with paired adjacent non-tumor tissues by RNA sequencing, RT-qPCR, Western blotting, and immunostaining. Public HCC datasets demonstrated upregulated STEAP2 expression in HCC and positive association with tumor grade. Transient and stable knockdown (KD) of STEAP2 in HCC cell lines abrogated their malignant phenotypes in vitro and in vivo, while STEAP2 overexpression showed opposite effects. STEAP2 KD in HCC cells led to significant alteration of genes associated with extracellular matrix organization, cell adhesion/chemotaxis, negative enrichment of an invasiveness signature gene set, and inhibition of cell migration/invasion. STEAP2 KD reduced intracellular copper levels and activation of stress-activated MAP kinases including p38 and JNK. Treatment with copper rescued the reduced HCC cell migration due to STEAP2 KD and activated p38 and JNK. Furthermore, treatment with p38 or JNK inhibitors significantly inhibited copper-mediated cell migration. Thus, STEAP2 plays a malignant-promoting role in HCC cells by driving migration/invasion via increased copper levels and MAP kinase activities. Our study uncovered a novel molecular mechanism contributing to HCC malignancy and a potential therapeutic target for HCC treatment.
Topics: Carcinoma, Hepatocellular; Humans; Liver Neoplasms; Copper; Cell Movement; Cell Line, Tumor; Animals; Gene Expression Regulation, Neoplastic; Mice; Disease Progression; Male; Oxidoreductases; Female
PubMed: 38830975
DOI: 10.1038/s41598-024-63368-2 -
Saudi Medical Journal Jun 2024To describe the current real-world treatment landscape, sequence of therapies, and outcomes in patients with prostate cancer (PC).
OBJECTIVES
To describe the current real-world treatment landscape, sequence of therapies, and outcomes in patients with prostate cancer (PC).
METHODS
A retrospective cohort study for PC patients diagnosed at King Abdullah Medical City Cancer Center in Makkah, Saudi Arabia, between January 2011 and December 2021. Data extracted from electronic medical records.
RESULTS
A total of 282 patients with PC, with a mean age of 70 years and body mass index of 27. Among them, 274 (99%) had no family history of cancer, while 164 (58%) had hypertension and 125 (44%) had diabetes mellitus. Adenocarcinoma was the most common histology, found in 275 (97%) patients, with 99 (35%) having a Gleason score of 9. Notably, 184 (65%) patients presented with metastatic disease, and 147 (52%) with bone metastasis. While 198 (70%) patients underwent surgery, 184 (65%) did not receive radiotherapy. The most common first-line metastatic therapy was abiraterone in 23 (8%) patients, followed by enzalutamide in 7 (2.5%). During the study period, 167 (59%) patients survived, with an average treatment duration of 2.5 years.
CONCLUSION
This study provides insights into real-world treatment patterns and clinical outcomes in patients with PC. The findings of this study highlight the importance of adhering to treatment standards and making informed clinical decisions.
Topics: Humans; Male; Prostatic Neoplasms; Saudi Arabia; Retrospective Studies; Aged; Middle Aged; Treatment Outcome; Phenylthiohydantoin; Nitriles; Neoplasm Grading; Adenocarcinoma; Bone Neoplasms; Androstenes; Prostatectomy; Cohort Studies; Aged, 80 and over; Benzamides
PubMed: 38830651
DOI: 10.15537/smj.2024.45.6.20240042 -
ELife Jun 2024Cancer immune evasion contributes to checkpoint immunotherapy failure in many patients with metastatic cancers. The embryonic transcription factor DUX4 was recently...
Cancer immune evasion contributes to checkpoint immunotherapy failure in many patients with metastatic cancers. The embryonic transcription factor DUX4 was recently characterized as a suppressor of interferon-γ signaling and antigen presentation that is aberrantly expressed in a small subset of primary tumors. Here, we report that expression is a common feature of metastatic tumors, with ~10-50% of advanced bladder, breast, kidney, prostate, and skin cancers expressing expression is significantly associated with immune cell exclusion and decreased objective response to PD-L1 blockade in a large cohort of urothelial carcinoma patients. expression is a significant predictor of survival even after accounting for tumor mutational burden and other molecular and clinical features in this cohort, with expression associated with a median reduction in survival of over 1 year. Our data motivate future attempts to develop DUX4 as a biomarker and therapeutic target for checkpoint immunotherapy resistance.
Topics: Humans; Homeodomain Proteins; Immunotherapy; Immune Evasion; Neoplasms; Male; Female; Neoplasm Metastasis; Immune Checkpoint Inhibitors; Gene Expression Regulation, Neoplastic
PubMed: 38829686
DOI: 10.7554/eLife.89017 -
Archivio Italiano Di Urologia,... May 2024Immunotherapy is defined as a therapeutic approach that targets or manipulates the immune system. A deeper understanding of the cellular and molecular composition of the... (Review)
Review
Immunotherapy is defined as a therapeutic approach that targets or manipulates the immune system. A deeper understanding of the cellular and molecular composition of the tumour environment, as well as the mechanisms controlling the immune system, has made possible the development and clinical investigation of many innovative cancer therapies. Historically, immunotherapy has played an essential role in treating urologic malignancies, while in the modern era, the development of immune checkpoint inhibitors (ICIs) has been critical to urology. Urothelial carcinoma is a common type of cancer in the genitourinary system, and treatment strategies in this area are constantly evolving. Intravesical and systemic immunotherapeutic agents have begun to be used increasingly frequently in treating urothelial carcinoma. These agents increase the anti-tumour response by affecting the body's defence mechanisms. Immunotherapeutic agents used in urothelial carcinoma include various options such as BCG, interferon, anti-PD-1 (pembrolizumab, nivolumab) and anti-PD-L1 (atezolizumab, avelumab, durvalumab). Renal cell carcinoma (RCC) has been known for many years as a tumour with unique sensitivity to immunotherapies. The recent emergence of ICIs that block PD-1/PD-L1 (pembrolizumab, nivolumab, atezolizumab) or CTLA4 (ipilimumab) signalling pathways has reestablished systemic immunotherapy as central to the treatment of advanced RCC. In light of randomized clinical trials conducted with increasing interest in the application of immunotherapies in the adjuvant setting, combination therapies (nivolumab/ipilimumab, nivolumab/cabozantinib, pembrolizumab/ axitinib, pembrolizumab/lenvantinib) have become the standard first-line treatment of metastatic RCC. Prostate cancer is in the immunologically "cold" tumour category; on the contrary, in recent years, immunotherapeutic agents have come to the fore as an essential area in the treatment of this disease. Especially in the treatment of castration-resistant prostate cancer, immunotherapeutic agents constitute an alternative treatment method besides androgen deprivation therapy and chemotherapy. Ipilimumab, nivolumab, pembrolizumab, atezolizumab, and Sipuleucel T (Vaccine-based) are promising alternative treatment options. Considering ongoing randomized clinical trials, immunotherapeutic agents promise to transform the uro-oncology field significantly. In this review, we aimed to summarize the role of immunotherapy in urothelial, renal and prostate cancer in the light of randomized clinical trials.
Topics: Humans; Immunotherapy; Urologic Neoplasms; Carcinoma, Transitional Cell; Immune Checkpoint Inhibitors; Antineoplastic Agents, Immunological
PubMed: 38818794
DOI: 10.4081/aiua.2024.12307 -
Heliyon May 2024Circular RNAs (circRNAs) have garnered considerable attention in the study of various human diseases due to their ubiquitous expression and potential biological... (Review)
Review
BACKGROUND AND OBJECTIVE
Circular RNAs (circRNAs) have garnered considerable attention in the study of various human diseases due to their ubiquitous expression and potential biological functions. This study conducts a bibliometric and visualization-based analysis of circRNA-related research in diseases, aiming to reveal the current status, hotspots and emerging trends within the field.
METHODS
Literature published between 2013 and 2022 and indexed in the Web of Science core databases was retrieved. Visualizations of publication volume, countries, authors, institutions, journals, references, and keywords were performed. Microsoft Excel (2021) was used to analyze and graph publication volume and growth trends. Additionally, CiteSpace (version 6.1.R6) and VOSviewer (version 1.6.18) were employed to visualize the bibliographic information.
RESULTS
Between 2013 and 2022, a total of 4195 relevant articles on circRNA in the context of diseases were identified. These articles covered 56 countries, 2528 institutions, 19,842 authors and 698 journals, citing 85,541 references. The annual publication volume showed an exponential growth trend, with rapid development post-2017. China, the United States and Germany emerged as the top three contributors, demonstrating high publication volume and total citations. Notably, Nanjing Medical University exhibited the highest publication volume, boasting 291 articles. Burton B. Yang and Li Yang consistently ranked among the top 10 authors in terms of publication volume and citations, emerging as core contributors in this research field. The journal ranked first in terms of published articles (160), with an impact factor of 6.832, while garnered the highest impact factor (41.4), solidifying its position as a top journal in this field. Furthermore, high-frequency keywords included "expression" "proliferation" "biomarker" "microRNA" "cancer", signifying the prevailing research hotspots and principal themes of this field over the past decade. As of 2022, "biomarker", "prostate cancer","drug resistance","papillary thyroid carcinoma", etc. continued as keywords during the outbreak period. At present, the value of circRNA application is mainly reflected in the two aspects of biomarkers and therapeutic targets, and the prediction of accurate diagnosis and precise treatment based on big data analysis, especially in cancer, will become a hot spot of research in the future.
CONCLUSION
The trajectory of circRNA research from its biological origins to its applications in diseases has been delineated from 2013 to 2022. However, the transition to disease-specific applications and exploration of biological functions warrants further attention in future research endeavors.
PubMed: 38818139
DOI: 10.1016/j.heliyon.2024.e31478 -
Frontiers in Immunology 2024Angiogenesis, the process of forming new blood vessels from pre-existing ones, plays a crucial role in the development and advancement of cancer. Although blocking...
Evaluating the predictive value of angiogenesis-related genes for prognosis and immunotherapy response in prostate adenocarcinoma using machine learning and experimental approaches.
BACKGROUND
Angiogenesis, the process of forming new blood vessels from pre-existing ones, plays a crucial role in the development and advancement of cancer. Although blocking angiogenesis has shown success in treating different types of solid tumors, its relevance in prostate adenocarcinoma (PRAD) has not been thoroughly investigated.
METHOD
This study utilized the WGCNA method to identify angiogenesis-related genes and assessed their diagnostic and prognostic value in patients with PRAD through cluster analysis. A diagnostic model was constructed using multiple machine learning techniques, while a prognostic model was developed employing the LASSO algorithm, underscoring the relevance of angiogenesis-related genes in PRAD. Further analysis identified MAP7D3 as the most significant prognostic gene among angiogenesis-related genes using multivariate Cox regression analysis and various machine learning algorithms. The study also investigated the correlation between MAP7D3 and immune infiltration as well as drug sensitivity in PRAD. Molecular docking analysis was conducted to assess the binding affinity of MAP7D3 to angiogenic drugs. Immunohistochemistry analysis of 60 PRAD tissue samples confirmed the expression and prognostic value of MAP7D3.
RESULT
Overall, the study identified 10 key angiogenesis-related genes through WGCNA and demonstrated their potential prognostic and immune-related implications in PRAD patients. MAP7D3 is found to be closely associated with the prognosis of PRAD and its response to immunotherapy. Through molecular docking studies, it was revealed that MAP7D3 exhibits a high binding affinity to angiogenic drugs. Furthermore, experimental data confirmed the upregulation of MAP7D3 in PRAD, correlating with a poorer prognosis.
CONCLUSION
Our study confirmed the important role of angiogenesis-related genes in PRAD and identified a new angiogenesis-related target MAP7D3.
Topics: Humans; Male; Prostatic Neoplasms; Prognosis; Neovascularization, Pathologic; Machine Learning; Immunotherapy; Adenocarcinoma; Biomarkers, Tumor; Gene Expression Regulation, Neoplastic; Microtubule-Associated Proteins; Molecular Docking Simulation; Gene Expression Profiling; Angiogenesis
PubMed: 38817605
DOI: 10.3389/fimmu.2024.1416914