Diagnostic and Therapeutic Challenges in a Patient with Synchronous Very High-Risk Prostate Adenocarcinoma and Anal Carcinoma

A 79-year-old HIV-negative Caucasian man with a medical history of smoking 20 pack-years (quit 40 years prior), early-stage non-small cell lung cancer status post-lobectomy 13 years earlier at an outside hospital without evidence of recurrence, and benign prostatic hypertrophy was diagnosed with synchronous very high-risk prostate adenocarcinoma and early-stage anal basaloid squamous cell carcinoma. He proceeded to undergo concurrent treatment for these tumors, consisting of androgen deprivation therapy, external beam radiation therapy, and a brachytherapy boost for the prostate adenocarcinoma; for the anal carcinoma, he was treated with definitive chemoradiation. Over 3.5 years since the completion of radiotherapy, he remains in clinical and biochemical remission.

A Novel Model Based on Necroptosis-Related Genes for Predicting Prognosis of Patients With Prostate Adenocarcinoma

Background: Necroptosis is a newly recognized form of cell death. Here, we applied bioinformatics tools to identify necroptosis-related genes using a dataset from The Cancer Genome Atlas (TCGA) database, then constructed a model for prognosis of patients with prostate cancer.Methods: RNA sequence (RNA‐seq) data and clinical information for Prostate adenocarcinoma (PRAD) patients were obtained from the TCGA portal (http://tcga-data.nci.nih.gov/tcga/). We performed comprehensive bioinformatics analyses to identify hub genes as potential prognostic biomarkers in PRAD u followed by establishment and validation of a prognostic model. Next, we assessed the overall prediction performance of the model using receiver operating characteristic (ROC) curves and the area under curve (AUC) of the ROC.Results: A total of 5 necroptosis-related genes, namely ALOX15, BCL2, IFNA1, PYGL and TLR3, were used to construct a survival prognostic model. The model exhibited excellent performance in the TCGA cohort and validation group and had good prediction accuracy in screening out high-risk prostate cancer patients.Conclusion: We successfully identified necroptosis-related genes and constructed a prognostic model that can accurately predict 1- 3-and 5-years overall survival (OS) rates of PRAD patients. Our riskscore model has provided novel strategy for the prediction of PRAD patients’ prognosis.

Cytotoxic and pro-apoptotic Effects of Spirulina Platensis Extract on PC-3 Prostate Adenocarcinoma Cell Line

Introduction: Prostate cancer is one of the most common cancers among men, with an increasing incidence and mortality rate. In the present study, cytotoxic and pro-apoptotic effects of spirulina platensis extract on PC-3 prostate adenocarcinoma cell line were investigated. Methods: In the present experimental study, the PC-3 prostatic cancer cells were treated in four experimental with 400, 200, 100 and 50 μg / ml extract of spirulina and incubated at 24 and 48 hours. Cytotoxicity was analyzed by MTS kit (3-(4, 5-Dimethylthiazol-2-yl)-5-(3-Carboxymethoxyphenyl)-2-(4-Sulfophenyl)-2H-Tetrazolium, Inner Salt) and apoptosis was analyzed by flow- cytometry using an Annexin V-FITC/PI kit according to the manufacturer protocol in both times. Statistical analysis was accomplished by ANOVA and Duncan tests using FlowJo and SPSS 16 software. Results: In the experimental groups treated with extract of spirulina, the viability of the cells showed a decrease compared to control group, while this decrease was more noticeable in the experimental group of 100 μg / ml at both incubation times (<0.0071).Increased incidence of apoptosis was significantly higher in the experimental groups than the control group. However, this increase was significantly higher than the control group at concentrations of 200 μg / ml in 24h incubation time (Ƥ < 0.0331) and 100 μg / ml of 48h incubation time (Ƥ < 0.0502). Conclusion: Extract of Spirulina at specific concentrations reduced cell growth and induced apoptosis in PC-3 prostatic cancer cells. Evidence suggests that spirulina can be used as an anticancer drug for the treatment of prostate cancer.

Neuroendocrine Carcinoma as an Independent Prognostic Factor for Patients With Prostate Cancer: A Population-Based Study

BackgroundNeuroendocrine carcinoma (NEC) is a rare and highly malignant variation of prostate adenocarcinoma. We aimed to investigate the prognostic value of NEC in prostate cancer.MethodsA total of 530440 patients of prostate cancer, including neuroendocrine prostate cancer (NEPC) and adenocarcinoma from 2004 to 2018 were obtained from the national Surveillance, Epidemiology, and End Results (SEER) database. Propensity score matching (PSM), multivariable Cox proportional hazard model, Kaplan‐Meier method and subgroup analysis were performed in our study.ResultsNEPC patients were inclined to be older at diagnosis (Median age, 69(61-77) vs. 65(59-72), P&lt; 0.001) and had higher rates of muscle invasive disease (30.9% vs. 9.2%, P &lt; 0.001), lymph node metastasis (32.2% vs. 2.2%, P &lt; 0.001), and distal metastasis (45.7% vs. 3.6%, P &lt; 0.001) compared with prostate adenocarcinoma patients. However, the proportion of NEPC patients with PSA levels higher than 4.0 ng/mL was significantly less than adenocarcinoma patients (47.3% vs. 72.9%, P&lt;0.001). NEPC patients had a lower rate of receiving surgery treatment (28.8% vs. 43.9%, P&lt;0.001), but they had an obviously higher rate of receiving chemotherapy (57.9% vs. 1.0%, P&lt;0.001). A Cox regression analysis demonstrated that the NEPC patients faced a remarkably worse OS (HR = 2.78, 95% CI = 2.34–3.31, P &lt; 0.001) and CSS (HR = 3.07, 95% CI = 2.55–3.71, P &lt; 0.001) compared with adenocarcinoma patients after PSM. Subgroup analyses further suggested that NEPC patients obtained significantly poorer prognosis across nearly all subgroups.ConclusionThe prognosis of NEPC was worse than that of adenocarcinoma among patients with prostate cancer. The histological subtype of NEC is an independent prognostic factor for patients with prostate cancer.

Tumor-antigens and immune landscapes identification for prostate adenocarcinoma mRNA vaccine

Prostate adenocarcinoma (PRAD) is a leading cause of death among men. Messenger ribonucleic acid (mRNA) vaccine presents an attractive approach to achieve satisfactory outcomes; however, tumor antigen screening and vaccination candidates show a bottleneck in this field. We aimed to investigate the tumor antigens for mRNA vaccine development and immune subtypes for choosing appropriate patients for vaccination. We identified eight overexpressed and mutated tumor antigens with poor prognostic value of PRAD, including KLHL17, CPT1B, IQGAP3, LIME1, YJEFN3, KIAA1529, MSH5 and CELSR3. The correlation of those genes with antigen-presenting immune cells were assessed. We further identified three immune subtypes of PRAD (PRAD immune subtype [PIS] 1–3) with distinct clinical, molecular, and cellular characteristics. PIS1 showed better survival and immune cell infiltration, nevertheless, PIS2 and PIS3 showed cold tumor features with poorer prognosis and higher tumor genomic instability. Moreover, these immune subtypes presented distinguished association with immune checkpoints, immunogenic cell death modulators, and prognostic factors of PRAD. Furthermore, immune landscape characterization unraveled the immune heterogeneity among patients with PRAD. To summarize, our study suggests KLHL17, CPT1B, IQGAP3, LIME1, YJEFN3, KIAA1529, MSH5 and CELSR3 are potential antigens for PRAD mRNA vaccine development, and patients in the PIS2 and PIS3 groups are more suitable for vaccination.

Multi-territory stroke preceded by pulmonary embolism with asymptomatic coronavirus disease 2019: a case report

Background Non-bacterial thrombotic endocarditis is characterized by the presence of sterile vegetations on a cardiac valve. We present a case of multi-territory stroke caused by embolism of a non-bacterial thrombotic aortic valve endocarditis, leading to the diagnosis of a prostate adenocarcinoma with bone metastases. Case summary A 66-year-old patient was diagnosed with pulmonary embolism, first attributed to an asymptomatic coronavirus disease 2019 infection. Edoxaban was started, which was discontinued by the patient. Four weeks later, he presented with subacute vertigo and balance disorders. Magnetic resonance imaging showed a multi-territory stroke. A transoesophageal echocardiogram demonstrated a small vegetation on the aortic valve with moderate aortic insufficiency. Blood cultures remained negative. Malignancy screening showed a markedly elevated prostate-specific antigen. Prostate adenocarcinoma was confirmed on biopsy. A positron emission tomography revealed metastatic disease. A diagnosis of non-bacterial thrombotic endocarditis and paraneoplastic pulmonary embolism secondary to prostate cancer was made. Edoxaban was restarted and the patient was referred for treatment of the prostate adenocarcinoma. Follow-up after 5 months showed no evidence of aortic valve vegetations. Discussion Coronavirus disease 2019 in ambulatory patients may be insufficient as a predisposing factor for venous thrombo-embolism and these patients, especially the elderly, should undergo a screening for malignancy. Non-bacterial thrombotic endocarditis is a rare cause of multi-territory stroke. When related to cancer, the prostate can be the primary tumour.