To identify novel genes in castration-resistant prostate cancer (CRPC), we downloaded three microarray datasets containing CRPC and primary prostate cancer in Gene Expression Omnibus (GEO). R packages affy and limma were performed to identify differentially expressed genes (DEGs) between primary prostate cancer and CRPC. After that, we performed functional enrichment analysis including gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathway. In addition, protein-protein interaction (PPI) analysis was used to search for hub genes. Finally, to validate the significance of these genes, we performed survival analysis. As a result, we identified 53 upregulated genes and 58 downregulated genes that changed in at least two datasets. Functional enrichment analysis showed significant changes in the positive regulation of osteoblast differentiation pathway and aldosterone-regulated sodium reabsorption pathway. PPI network identified hub genes like cortactin-binding protein 2 (CTTNBP2), Rho family guanosine triphosphatase (GTPase) 3 (RND3), protein tyrosine phosphatase receptor-type R (PTPRR), Jagged1 (JAG1), and lumican (LUM). Based on PPI network analysis and functional enrichment analysis, we identified two genes (PTPRR and JAG1) as key genes. Further survival analysis indicated a relationship between high expression of the two genes and poor prognosis of prostate cancer. In conclusion, PTPRR and JAG1 are key genes in the CRPC, which may serve as promising biomarkers of diagnosis and prognosis of CRPC.
Computational Biology/methods* ; Gene Ontology ; Humans ; Jagged-1 Protein/genetics* ; Male ; Prognosis ; Prostatic Neoplasms, Castration-Resistant/mortality* ; Protein Interaction Maps ; Receptor-Like Protein Tyrosine Phosphatases, Class 7/genetics*

Perioperative hypersensitivity reaction have been reported to have a variable degree of the incidence from differ countries and to be 1/353–18,600 approximately and its mortality has been reported to be 4%–4.76% in the United States and Japan, respectively. A 65-year-old male patient with hypertension, rheumatoid arthritis, and history of amoxicillin allergy was scheduled for laparoscopic radical prostatectomy due to prostate cancer. Lidocaine, propofol, and rocuronium were administered sequentially to induce general anesthesia. Twenty minutes after the rocuronium administration, severe hypotension and tachycardia developed. But key signs of hypersensitivity such as urticaria and bronchospasm were not appeared. The operation was canceled and we evaluated the cause of severe hypotension and could confirm hypersensitivity for rocuronium with intradermal test after 4 weeks.
Aged ; Amoxicillin ; Anaphylaxis ; Anesthesia, General ; Arthritis, Rheumatoid ; Bronchial Spasm ; Humans ; Hypersensitivity ; Hypertension ; Hypotension ; Incidence ; Intradermal Tests ; Japan ; Lidocaine ; Male ; Mortality ; Propofol ; Prostatectomy ; Prostatic Neoplasms ; Tachycardia ; United States ; Urticaria

PURPOSE: Local treatment has become a treatment option for patients with de novo metastatic hormone-sensitive prostate cancer (mHSPC). Subgroup analyses based on a history of cerebrovascular disease (CVD) were performed to evaluate the impact thereof on overall survival (OS) after local treatment. MATERIALS AND METHODS: A retrospective analysis was performed for 879 patients with de novo mHSPC between August 2003 and November 2016. Patients were stratified according to prior CVD history and the type of initial treatment: androgen-deprivation therapy (ADT) alone versus local treatment consisting of radical prostatectomy (RP) or radiation therapy (RT) with ADT, with or without metastasis-directed therapy. The primary outcome was OS assessed by Kaplan-Meier analysis and Cox-regression models. RESULTS: Of 879 patients, 660 (75.1%) men underwent ADT alone, and 219 (24.9%) men underwent RP or RT with ADT, with or without metastasis-directed therapy. The median follow-up was 38 months. Multivariable analysis showed CVD history to be associated with a higher risk of overall mortality (p=0.001). In the overall cohort and in patients without a history of CVD, patients who underwent local treatment exhibited higher OS than men who received ADT alone (all p<0.001). However, the survival benefit conferred by local treatment was not seen in patients with a history of CVD (p=0.324). OS was comparable between patients who received RP and RT (p=0.521). CONCLUSION: Local treatment with or without metastasis-directed therapy may provide OS advantages for mHSPC patients without a history of CVD. Further prospective studies are needed to address these important concerns.
Cerebrovascular Disorders ; Cohort Studies ; Follow-Up Studies ; Humans ; Kaplan-Meier Estimate ; Male ; Mortality ; Neoplasm Metastasis ; Prospective Studies ; Prostate ; Prostatectomy ; Prostatic Neoplasms ; Retrospective Studies

PURPOSE: The purpose of this study was to establish the contribution of four founder alleles of NBN to prostate cancer risk and cancer survival. MATERIALS AND METHODS: Five thousand one hundred eighty-nine men with prostate cancer and 6,152 controls were genotyped for four recurrent variants of NBN (657del5, R215W, I171V, and E185Q). RESULTS: The NBN 657del5 mutation was detected in 74 of 5,189 unselected cases and in 35 of 6,152 controls (odds ratio [OR], 2.5; p < 0.001). In carriers of 657del5 deletion, the cancer risk was restricted to men with the GG genotype of the E185Q variant of the same gene. Among men with the GG genotype, the OR associated with 657del5 was 4.4 (95% confidence interval [CI], 2.4 to 8.0). Among men with other E185Q genotypes, the OR associated with 657del5 was 1.4 (95% CI, 0.8 to 2.4) and the interaction was significant (homogeneity p=0.006). After a median follow-up of 109 months, mortality was worse for 657del5 mutation carriers than for non-carriers (hazard ratio [HR], 1.6; p=0.001). The adverse effect of 657del5 on survival was only seen on the background of the GG genotype of E185Q (HR, 1.9; p=0.0004). CONCLUSION: The NBN 657del5 mutation predisposes to poor prognosis prostate cancer. The pathogenicity of this mutation, with regards to both prostate cancer risk and survival, is modified by a missense variant of the same gene (E185Q).
Alleles ; Follow-Up Studies ; Genotype ; Humans ; Male ; Mortality ; Prognosis ; Prostate ; Prostatic Neoplasms ; Virulence

BACKGROUND: Cancer is one of the leading causes of morbidity and mortality worldwide. Yet, limited is known about patterns of cancer and risk factors for advanced stage cancers in Ethiopia. METHODS: A cross-sectional study was conducted on 919 patients with biopsy-confirmed cancers at Tikur Anbessa Hospital in Ethiopia, 2010 to 2014. Pearson chi-square test, t-test, analysis of variance and multivariate logistic regression analyses were performed. RESULTS: The majority of the patients were females (72.4%). The commonest malignancies among males were bone and soft tissue (16.5%), colorectal (12.2%), and esophageal (9.1%). Among females, the most common cancers were cervical (39.7%), breast (18.3%), and ovarian (7.1%); of these, 41.7%, 59.0%, and 42.6% were diagnosed at advanced stages, respectively. Females had more advanced stage cancers at diagnosis than males (37.6% vs. 24.8%, P < 0.01). Among males, 46.7% of prostate and 29.0% of colorectal cancers were in advanced stages at the time of diagnosis. Delay in presentation from onset of symptoms was associated with advanced cancer among females (OR = 3.21; 95% CI = 1.69–6.10). Prostate cancer among males (OR = 5.22; 95% CI = 1.26–21.60) and breast cancer among females (OR = 1.93; 95% CI = 1.23–3.03) were more likely to be diagnosed at advanced stages. CONCLUSIONS: Cancers with effective screening tests are common in Ethiopia and significant proportions of these were diagnosed at advanced stages, typically several months after onset of symptoms. Timely access to preventive care along with effective educational and screening strategies is needed in Ethiopia for early detection and treatment of common malignancies, such as cervical, breast and colorectal cancers.
Breast ; Breast Neoplasms ; Colorectal Neoplasms ; Cross-Sectional Studies ; Diagnosis ; Ethiopia ; Female ; Humans ; Logistic Models ; Male ; Mass Screening ; Mortality ; Neoplasm Staging ; Prostate ; Prostatic Neoplasms ; Risk Factors

This study investigated the clinical activity of abiraterone plus prednisone in docetaxel-naïve and docetaxel-resistant Chinese patients with metastatic castration-resistant prostate cancer (mCRPC). A total of 146 patients with docetaxel-naïve group (103 cases) and docetaxel-resistant group (43 cases) were enrolled from the Shanghai Cancer Center (Shanghai, China) in this retrospective cohort study. The efficacy endpoints were prostate-specific antigen response rate, prostate-specific antigen progression-free survival, clinical/radiographic progression-free survival, and overall survival in response to abiraterone plus prednisone. Significantly higher prostate-specific antigen response rate was found in docetaxel-naïve group (54.4%, 56/103) compared to docetaxel-resistant group (34.9%, 15/43) (P = 0.047). In addition, significantly higher median prostate-specific antigen progression-free survival (14.0 vs 7.7 months, P = 0.005), clinical or radiographic progression-free survival (17.0 vs 12.5 months, P = 0.003), and overall survival (27.0 vs 18.0 months, P = 0.016) were found in docetaxel-naïve group compared to docetaxel-resistant group, respectively. The univariate and multivariate analyses indicated that lower albumin and visceral metastases were independent significant predictors for shorter overall survival. To sum up, our data suggested that abiraterone plus prednisone was efficient in both docetaxel-naïve and docetaxel-resistant Chinese patients. Moreover, higher PSA response rate and longer overall survival were observed in the docetaxel-naïve group, which suggested that abiraterone was more effective for docetaxel- naïve patients than for docetaxel failures.
Aged ; Aged, 80 and over ; Androstenes/therapeutic use* ; Antineoplastic Agents, Hormonal/therapeutic use* ; China ; Disease Progression ; Disease-Free Survival ; Drug Therapy, Combination ; Humans ; Male ; Middle Aged ; Prednisone/therapeutic use* ; Prostatic Neoplasms, Castration-Resistant/mortality* ; Retrospective Studies ; Survival Rate ; Treatment Outcome

Aged ; Aged, 80 and over ; Androgen Antagonists/therapeutic use* ; Biomarkers, Tumor/blood* ; Dehydroepiandrosterone Sulfate/blood* ; Humans ; Male ; Middle Aged ; Prostatic Neoplasms/mortality* ; Prostatic Neoplasms, Castration-Resistant/mortality* ; Survival Analysis ; Treatment Outcome

BACKGROUND: Robot-assisted radical prostatectomy (RARP) is a feasible treatment option for high-risk prostate cancer (PCa). While patients may achieve undetectable prostate-specific antigen (PSA) levels after RARP, the risk of disease progression is relatively high. We investigated metastasis-free survival, cancer-specific survival (CSS), and overall survival (OS) outcomes and prognosticators in such patients. METHODS: In a single-center cohort of 342 patients with high-risk PCa (clinical stage ≥ T3, biopsy Gleason score ≥ 8, and/or PSA levels ≥ 20 ng/mL) treated with RARP and pelvic lymph node dissection between August 2005 and June 2011, we identified 251 (73.4%) patients (median age, 66.5 years; interquartile range [IQR], 63.0–71.0 years) who achieved undetectable PSA levels (< 0.01 ng/mL) postoperatively. Survival outcomes were evaluated for the entire study sample and in groups stratified according to the time to biochemical recurrence dichotomized at 60 months. RESULTS: During the median follow-up of 75.9 months (IQR, 59.4–85.8 months), metastasis occurred in 38 (15.1%) patients, most often to the bones, followed by the lymph nodes, lungs, and liver. The 5-year metastasis-free, cancer-specific, and OS rates were 87.1%, 94.8%, and 94.3%, respectively. Multivariate Cox-regression analysis revealed time to recurrence as an independent predictor of metastasis (P < 0.001). Time to metastasis was an independent predictor of OS (P = 0.003). Metastasis-free and CSS rates were significantly lower among patients with recurrence within 60 months of RARP (log-rank P < 0.001). CONCLUSION: RARP confers acceptable oncological outcomes for high-risk PCa. Close monitoring beyond 5 years is warranted for early detection of disease progression and for timely adjuvant therapy.
Biopsy ; Cohort Studies ; Disease Progression ; Early Diagnosis ; Follow-Up Studies ; Humans ; Liver ; Lung ; Lymph Node Excision ; Lymph Nodes ; Mortality* ; Neoplasm Grading ; Neoplasm Metastasis* ; Passive Cutaneous Anaphylaxis ; Prostate* ; Prostate-Specific Antigen* ; Prostatectomy* ; Prostatic Neoplasms* ; Recurrence*

Cancer is a major cause of morbidity and the most common cause of death in Korea. There are currently approximately 200,000 incident cancer cases and 78,000 individuals die from cancer every year. The factors directly related to cancer incidence, including aging, smoking, obesity, and Westernized dietary habits, have been increasing during the past several decades. Since 1999, trends toward increased incidence have been observed for thyroid, breast (in women), colorectal, and prostate cancer. Currently, these trends have changed direction, and the incidence of stomach and liver cancer in both sexes, and cervical cancer in women have continually declined. Although the number of cancer deaths increased by a factor of 2.7 from 1983 to 2016, the age-standardized mortality associated with cancer has been decreasing by 3% every year. The 5-year relative survival rate (RSR) has also improved over the past several decades, especially for stomach, prostate, and breast cancer, which had 5-year RSRs greater than 90% in the most recent report.
Aging ; Breast ; Breast Neoplasms ; Cause of Death ; Epidemiology* ; Female ; Food Habits ; Humans ; Incidence ; Korea* ; Liver Neoplasms ; Mortality ; Obesity ; Prostate ; Prostatic Neoplasms ; Republic of Korea ; Smoke ; Smoking ; Stomach ; Survival Rate ; Thyroid Gland ; Uterine Cervical Neoplasms

The prognostic significance of initial prostate-specific antigen (PSA) level for metastatic prostate cancer remains uncertain. We investigated the differences in prognosis and response to hormonal therapies of metastatic prostate cancer patients according to initial PSA levels. We analyzed 184 patients diagnosed with metastatic prostate cancer and divided them into three PSA level groups as follows: low (<100 ng ml^-1), intermediate (100-999 ng ml^-1), and high (≥1000 ng ml^-1). All patients received androgen deprivation therapy (ADT) immediately. We investigated PSA progression-free survival (PFS) for first-line ADT and overall survival (OS) within each of the three groups. Furthermore, we analyzed response to antiandrogen withdrawal (AW) and alternative antiandrogen (AA) therapies after development of castration-resistant prostate cancer (CRPC). No significant differences in OS were observed among the three groups (P = 0.654). Patients with high PSA levels had significantly short PFS for first-line ADT (P = 0.037). Conversely, patients in the high PSA level group had significantly longer PFS when treated with AW than those in the low PSA level group (P = 0.047). Furthermore, patients with high PSA levels had significantly longer PFS when provided with AA therapy (P = 0.049). PSA responders to AW and AA therapies had significantly longer survival after CRPC development than nonresponders (P = 0.011 and P < 0.001, respectively). Thus, extremely high PSA level predicted favorable response to vintage sequential ADT and AW. The current data suggest a novel aspect of extremely high PSA value as a favorable prognostic marker after development of CRPC.
Aged ; Aged, 80 and over ; Androgen Antagonists/therapeutic use* ; Disease Progression ; Humans ; Male ; Middle Aged ; Prognosis ; Progression-Free Survival ; Prostate-Specific Antigen/blood* ; Prostatic Neoplasms/mortality* ; Treatment Outcome