Identification and validation of obesity related genes signature based on microenvironment phenotypes in prostate adenocarcinoma.

BACKGROUND: The role of obesity related genes (ORGs) in the immune checkpoint inhibitors (ICIs) treatment of prostate adenocarcinoma (PRAD) has not yet been proved by research. METHODS: We comprehensively evaluated the ORGs patterns in PRAD based on tumor microenvironment (TME) phenotypes and immunotherapy efficacies. Then we constructed a ORGs risk score for prognosis and a ORGs signature for accurate prediction of TME phenotype and immunotherapy efficacy in order to evaluate individual patients. RESULTS: Two distinct ORGs patterns were generated. The two ORGs patterns were consistent with inflammatory and non-inflammatory TME phenotypes. ORGs patterns had an important role for predicting immunotherapy efficacies. Next, we constructed a ORGs risk score for predicting each patient's prognosis with high performance in TCGA-PRAD. The ORGs risk score could be well verified in the external cohorts including GSE70769 and GSE21034. Then, we developed a ORGs signature and found it was significantly positively correlated with tumor-infiltrating lymphocytes in TCGA-PRAD. We found that each patient in the high-risk ORGs signature group represented a non-inflamed TME phenotype on the single cell level. The patients with high ORGs signature had more sensitivity to immunotherapy. And those ORGs were verified. CONCLUSIONS: ORGs pattern depicts different TME phenotypes in PRAD. The ORGs risk score and ORGs signature have an important role for predicting prognosis and immunotherapy efficacies.

A preoperative magnetic resonance imaging-based model to predict biochemical failure after radical prostatectomy.

To investigate if a magnetic resonance imaging (MRI)-based model reduced postoperative biochemical failure (BF) incidence in patients with prostate cancer (PCa). From June 2018 to January 2020, we retrospectively analyzed 967 patients who underwent prostate bi-parametric MRI and radical prostatectomy (RP). After inclusion criteria were applied, 446 patients were randomized into research (n = 335) and validation cohorts (n = 111) at a 3:1 ratio. In addition to clinical variables, MRI models also included MRI parameters. The area under the curve (AUC) of receiver operating characteristic and decision curves were analyzed. The risk of postoperative BF, defined as persistently high or re-elevated prostate serum antigen (PSA) levels in patients with PCa with no clinical recurrence. In the research (age 69 [63-74] years) and validation cohorts (age 69 [64-74] years), the postoperative BF incidence was 22.39% and 27.02%, respectively. In the research cohort, the AUC of baseline and MRI models was 0.780 and 0.857, respectively, with a significant difference (P < 0.05). Validation cohort results were consistent (0.753 vs. 0.865, P < 0.05). At a 20% risk threshold, the false positive rate in the MRI model was lower when compared with the baseline model (31% [95% confidence interval (CI): 9-39%] vs. 44% [95% CI: 15-64%]), with the true positive rate only decreasing by a little (83% [95% CI: 63-94%] vs. 87% [95% CI: 75-100%]). 32 of 100 RPs can been performed, with no raise in quantity of patients with missed BF. We developed and verified a MRI-based model to predict BF incidence in patients after RP using preoperative clinical and MRI-related variables. This model could be used in clinical settings.

Identifying a Novel Defined Pyroptosis-Associated Long Noncoding RNA Signature Contributes to Predicting Prognosis and Tumor Microenvironment of Bladder Cancer.

Background: Bladder cancer (BLCA) is a common malignant tumor of the urinary tract, which is the sixth most common cancer among men. Numerous studies suggested that pyroptosis and long noncoding RNAs (lncRNAs) played an essential role in the development of cancers. However, the role of pyroptosis-related lncRNAs in BLCA and their prognostic value are still unclear. Methods: In this study, we constructed a signature model through least absolute shrinkage and selection operator (LASSO) Cox regression analysis and Cox univariate analysis based on The Cancer Genome Atlas (TCGA) database. The expression of 12 pyroptosis-related lncRNAs was also confirmed by qRT-PCR in BLCA cell lines. TIMER, XCELL, QUANTISEQ, MCPCOUNTER, EPIC, and CIBERSORT R script were applied to quantify the relative proportions of infiltrating immune cells. Correlation coefficients were computed by Spearman analyses. The Kaplan-Meier method, Cox regression model, and log-rank tests were used to evaluate the prognostic value. The R package of pRRophetic was used to predict IC50 of common chemotherapeutic agents. Results: A total of 12 pyroptosis-related lncRNAs with great prognosis value were identified. The expression was investigated by qRT-PCR in four BLCA cell lines. Then, 126 cases were identified as high-risk group, and 277 cases were identified as low-risk group based on the cutoff point. Patients in the low-risk group showed a significant survival advantage. Furthermore, we found that clinical features were significantly related to the risk score. As well, based on the C-index values, a nomogram was constructed. The gene set enrichment analysis (GSEA) results showed that mitogen-activated protein kinase (MAPK) signaling, transforming growth factor (TGF)-ß signaling, and WNT signaling were with important significance in the high-risk group. Moreover, we found that riskscore was positively correlated with M0 macrophages and M2 macrophages. Conclusions: In conclusion, our study indicated that pyroptosis is closely connected to BLCA. The riskscore generated from the expression of 12 pyroptosis-related lncRNAs was evaluated by various clinical features including survival status, tumor microenvironment, clinicopathological characteristic, and chemotherapy. It may offer a significant basis for future studies.

Use of Prostate Systematic and Targeted Biopsy on the Basis of Bi-Parametric Magnetic Resonance Imaging in Biopsy-Naïve Patients.

OBJECTIVES: To explore the performance of targeted biopsy (TB) in combination with systematic biopsy (SB) in the detection of prostate cancer (PCa) in biopsy naïve patients. METHODS: From May 2018 to January 2020, 230 biopsy-naïve men with suspicious bi-parametric MRI [bpMRI; Prostate Imaging Reporting and Data System (PI-RADS) score ≥3] were enrolled. All patients had prostate-specific antigen (PSA) levels of 20 ng/ml or less. For each patient, transrectal ultrasound-guided prostate biopsy was performed. The primary endpoint was the detection rate of CSPC [clinically-significant PCa, International Society of Urological Pathology grade group (ISUP GG) 2 or higher tumors]. The secondary endpoints were the detection rates of CIPC (clinically insignificant PCa, ISUP GG 1 tumors). RESULTS: CSPC was detected in 90 patients. Twelve (13.33%) of them were detected by TB only and 18 (20.00%) by SB only. Detection of CSPC by SB and TB did not differ significantly (p = .36). In 4.35% of 230 patients, CSPC would have been missed if we performed SB only, and in 6.09% of patients if we performed TB only. Moreover, combination of TB and SB did not increase the detection of CIPC. CONCLUSIONS: No significant difference was found in the detection of CSPC between TB and SB; however, both techniques revealed substantial added value and combination of TB and SB could further improve this detection rate without increasing the detection of CIPC.

Long non-coding RNA profile study identifies an immune-related lncRNA prognostic signature for prostate adenocarcinoma.

Prostate adenocarcinoma (PRAD) is the highest incidence rate of male urogenital morbidity worldwide. Long non-coding RNAs (lncRNAs), as a significant class of gene expression regulators, play a critical role in immune regulation. The purpose of this study is to explore a new immune related lncRNA signature to exactly predict the prognosis of PRAD patients. In this study, we conducted a genome-wide comparative analysis of lncRNA expression profiles in 532 patients with PRAD from the Cancer Genome Atlas (TCGA) database. The immune-related lncRNAs were identified by Cox regression model, and then a new five immune-related lncRNAs signature (FRMD6-AS2, AC008770.3, AC109460.3, AC011899.2, and AC008063.1) were constructed, which could predict the prognosis of PRAD patients. Univariate and multivariate Cox regression analysis showed that the signature could be an independent prognostic indicator of overall survival (OS). Through further study of different clinic-pathological parameters, we found that PRAD samples can be divided into high-risk groups with shorter OS and low-risk groups with longer OS by the signature. Principal component analysis showed that five immune-related lncRNA signature could distinguish the high-risk group from low-risk group in view of the immune-related lncRNAs. The difference of immune status between the two groups was observed by gene set enrichment analysis and the ESTIMATE algorithm. Except FRMD6-AS2, the expression of the other 4 lncRNAs were remarkably up-regulated in tumor tissues. In conclusion, the identified five immune-related lncRNAs signature had important clinical significance in prognosis prediction, and can be used as potential immunotherapy targets for PRAD patients.

Analysis of risk factors for determining the need for prostate biopsy in patients with negative MRI.

To analyze the clinical characteristics of patients with negative biparametric magnetic resonance imaging (bpMRI) who didn't need prostate biopsies (PBs). A total of 1,012 male patients who underwent PBs in the First Affiliated Hospital of Nanjing Medical University from March 2018 to November 2019, of 225 had prebiopsy negative bpMRI (defined as Prostate Imaging Reporting and Data System (PI-RADS 2.1) score less than 3). The detection efficiency of clinically significant prostate cancer (CSPCa) was assessed according to age, digital rectal examination (DRE), prostate volume (PV) on bpMRI, prostate-specific antigen (PSA) and PSA density (PSAD). The definition of CSPCa for Gleason score > 6. Univariate and multivariable logistic regression analysis were used to identify predictive factors of absent CSPCa on PBs. Moreover, absent CSPCa contained clinically insignificant prostate cancer (CIPCa) and benign result. The detection rates of present prostate cancer (PCa) and CSPCa were 27.11% and 16.44%, respectively. Patients who were diagnosed as CSPCa had an older age (P < 0.001), suspicious DRE (P < 0.001), a smaller PV (P < 0.001), higher PSA value (P = 0.008) and higher PSAD (P < 0.001) compared to the CIPCa group and benign result group. PSAD < 0.15 ng/ml/cm3 (P = 0.004) and suspicious DRE (P < 0.001) were independent predictors of absent CSPCa on BPs. The negative forecast value of bpMRI for BP detection of CSPCa increased with decreasing PSAD, mainly in patients with naive PB (P < 0.001) but not in prior negative PB patients. 25.33% of the men had the combination of negative bpMRI, PSAD < 0.15 ng/ml/cm3 and PB naive, and none had CSPCa on repeat PBs. The incidence of PB was determined, CSPCa was 1.59%, 0% and 16.67% in patients with negative bpMRI and PSAD < 0.15 ng/ml/cm3, patients with negative bpMRI, PSAD < 0.15 ng/ml/cm3 and biopsy naive and patients with negative bpMRI, PSAD < 0.15 ng/ml/cm3 and prior negative PB, separately. We found that a part of patients with negative bpMRI, a younger age, no suspicious DRE and PSAD < 0.15 ng/ml/cm3 may securely avoid PBs. Conversely PB should be considered in patients regardless of negative bpMRI, especially who with a greater age, obviously suspicious DRE, significantly increased PSA value, a significantly small PV on MRI and PSAD > 0.15 ng/ml/cm3.

A Comparative Study of Prostate Cancer Detection Rate Between Transperineal COG-TB and Transperineal FUS-TB in Patients with PSA ≤20 ng/mL.

Background: The combination of prebiopsy MRI and transperineal targeted biopsies is being increasingly used to obtain tissues from patients with suspected prostate cancer (PCa). Objective: To investigate the difference in PCa detection rate between transperineal cognitive fusion TB (COG-TB) and transperineal software fusion TB (FUS-TB). Participants: The present study included 163 male patients with suspected PCa who had not undergone prostate biopsy, had a prostate-specific antigen (PSA) level of ≤20 ng/mL, and had been examined by bi-parameter MRI and confirmed to have prostate nodules by prostate imaging reporting and data system version 2 (PI-RADS V2) scores ≥3 (from December 3, 2018 to October 7, 2019). Intervention: Seventy-one patients underwent transperineal COG-TB, and 92 patients underwent transperineal FUS-TB. The detection rate of the first four needles was compared. Results: No significant difference was found in the overall detection rate of PCa between COG-TB and FUS-TB (60.56% vs 51.08%, p = 0.228). This result was consistent even after stratifying by PI-RADS score. There was also no significant difference between COG-TB and FUS-TB in the detection rate of clinically significant PCa (p = 0.641). Moreover, COG-TB and FUS-TB showed no difference in the detection rate of PCa with different Gleason scores. Conclusions: In patients with suspected PCa with PSA ≤20 ng/mL and PI-RADS ≥3, FUS-TB was comparable to COG-TB in the detection rate of PCa.

A dual continuum model of the reasons for use of complementary health approaches among overweight and obese adults: findings from the 2012 NHIS.

BACKGROUND: Obese and overweight individuals have greater illness and disease burden, but previous findings from the 2002 National Health Interview Survey (NHIS) suggest that they are no more likely to use complementary health approaches (CHA) than those of normal weight. The current study investigates the relationship between weight status and CHA use, and among CHA users, examines differences in reasons for use by weight status. We propose and test a Dual Continuum Model of Motivations for Use of CHA to examine differences in reasons for use by weight status. METHOD: Participants were drawn from the 2012 NHIS, a nationally representative sample of civilian, non-institutionalized US adults (N = 34,525). Weight status was operationalized by body mass index. CHA use was measured in the past year and was categorized into alternative providers, products, and practices. Among CHA users (N = 9307) factors associated with use were categorized as health enhancing or health reactive. RESULTS: Logistic regression showed overweight and obese individuals were less likely to use alternative providers, products, and practices than normal weight. Multinomial logit regression showed some support that overweight and obese adults were less likely than normal weight persons to use CHA for health-enhancing reasons, and more likely to use for health reactive reasons. CONCLUSIONS: Despite greater health burden, overweight and obese adults are underutilizing CHA, including modalities that can be helpful for health management. The Dual Continuum Model of CHA Motivations shows promise for explicating the diversity of reasons for CHA use among adults at risk for health problems.