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Background Due to negative results in clinical trials of postoperative chemoradiation for gastric cancer, at present, there is a tendency to move chemoradiation therapy forward in gastric and gastroesophageal junction (GEJ) adenocarcinoma. Several randomized controlled trials (RCTs) are currently recruiting subjects to investigate the effect of neo-adjuvant radiotherapy (NRT) in gastric and GEJ cancer. Large retrospective studies may be beneficial in clarifying the potential benefit of NRT, providing implications for RCTs. Methods We retrieved the clinicopathological and treatment data of gastric and GEJ adenocarcinoma patients who underwent surgical resection and chemotherapy between 2004 and 2015 from Surveillance, Epidemiology, and End Results (SEER) database. We compared survival between NRT and non-NRT patients among four clinical subgroups (T1–2N−, T1–2N+, T3–4N−, and T3–4N+). Results Overall, 5272 patients were identified, among which 1984 patients received NRT. After adjusting confounding variables, significantly improved survival between patients with and without NRT was only observed in T3–4N+ subgroup [hazard ratio (HR) 0.79, 95% confidence interval (CI): 0.66–0.95; P = 0.01]. Besides, Kaplan-Meier plots showed significant cause-specific survival advantage of NRT in intestinal type (P P = 0.11) for T3–4N+ patients. In the multivariate competing risk model, NRT still showed survival advantage only in T3–4 N+ patients (subdistribution HR: 0.77; 95% CI: 0.64–0.93; P = 0.006), but not in other subgroups. Conclusions NRT might benefit resectable gastric and GEJ cancer patients of T3–4 stages with positive lymph nodes, particularly for intestinal-type. Nevertheless, these results should be interpreted with caution, and more data from ongoing RCTs are warranted.

The dysregulation of RNA binding proteins (RBPs) regulates the progression of several cancers. However, information on the overall functions of RBPs in prostate cancer (PCa) remains largely understudied. Therefore, based on the TCGA dataset, this study identified 144 differentially expressed RBPs in tumors compared to normal tissues. Subsequently, through univariate, LASSO and multivariate Cox regression analysis, 6 RBP genes among them, MSI1, MBNL2, LENG9, REXO2, RNASE1, and PABPC1L were screened as prognostic hub genes and prognostic signature was further identified. Further analysis indicated that the high-risk group was significantly associated with poor RFS, which was validated in the MSKCC cohort. Besides, patients in the high-risk group were closely associated with dysregulation of DNA damage repair pathway, copy number alteration, tumor burden mutation, and low-response to cisplatin (P 0.001), and bicalutamide (P 0.001). Using the Connectivity Map, we finally predicted 3 drugs including, ribavirin, carmustine, and carbenoxolone. In summary, we identified six-RBP gene signature and 3 potential drugs against PCa, which might promote the individualized treatment strategies and further improve the quality of life among PCa patients.

Zichen Bian,1,* Jialin Meng,1,* Qingsong Niu,1 Xiaoyan Jin,2 Jinian Wang,3 Xingliang Feng,1 Hong Che,4 Jun Zhou,1 Li Zhang,1 Meng Zhang,1,5 Chaozhao Liang1 1Department of Urology, The First Affiliated Hospital of Anhui Medical University; Anhui Province Key Laboratory of Genitourinary Diseases, Anhui Medical University; The Institute of Urology, Anhui Medical University, Hefei, People’s Republic of China; 2The Second Clinical College of Anhui Medical University, Hefei, Anhui, People’s Republic of China; 3Clinical Skills Training Center, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, Anhui, People’s Republic of China; 4Department of Cardiac Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, People’s Republic of China; 5Institute of Urology of Shenzhen University, The Third Affiliated Hospital of Shenzhen University, Shenzhen Luohu Hospital Group, Shenzhen 518000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Chaozhao Liang; Meng Zhang Email liang_chaozhao@ahmu.edu.cn; zhangmeng1930@126.comBackground: To help with the clinical practice of renal cancer patients, prognostic models are urgently warranted. We hunted and identified prognostic variables associated with recurrence-free survival (RFS) for renal cancer patients.Patients and Methods: In this retrospective study, 187 renal cancer patients who had received curative radical/partial nephrectomy between November 2011 and January 2017 were enrolled in the current study. These patients were randomly split into the training (n = 95) and validation sets (n = 92) by the ratio of 1:1. Univariate and multivariable Cox regression analyses were used to establish the nomogram, which was then evaluated by receiver operating characteristic (ROC) and Kaplan-Meier (K-M) analyses.Results: Patient characteristics and outcomes were well balanced between the training and validation sets; the median RFS values were 54.1 months and 58.9 months for the training and validation cohorts, respectively. The final nomogram included six independent prognostic variables (prothrombin time (%), prothrombin time (second), albumin/globulin ratio, platelets, sex and fibrinogen). The mean values of RFS for the low- and high-risk groups defined by a prognostic formula were 56.22 ± 18.50 months and 49.54 ± 23.57 months, respectively, in the training cohort and were 59.00 ± 19.50 months and 53.32 ± 19.95 months, respectively, in the validation cohort. The significance and stability of the model were tested by the time-dependent K-M model and ROC curves, respectively.Conclusion: Our validated prognostic model incorporates variables routinely collected from renal cancer patients, identifying subsets of patients with different survival outcomes, which provides useful information for patient care and clinical trial design.Keywords: renal cancer, recurrence, nomogram

Backgroud. Cutaneous melanoma (CM) causes the highest absolute number of deaths among all types of skin cancers; however, the association between Fc receptor- (FcR-) like (FCRL) molecules and CM remains unclear. Methods. 461 patients with CM from The Cancer Genome Atlast- (TCGA-) CM cohort and 290 pateints from the GSE65904 cohort were enrolled. Student’s t-test was used to compare the differences, and Pearson’s correlation coefficient was employed to evaluate associations. The Kaplan-Meier (K-M) survival analysis was used to evaluate overall survival (OS). The multivariate Cox regression was conducted to generate the FCRL prognostic signature. GSEA analysis and TIMER were employed to study the potential mechanisms. Result. Patients with Breslow’s depth high or equal to 3 cm had the lower expression of FCRL1-6 (all, P<0.05), which indicates poor OS, as well as age, stage, and Breslow’s depth subgroups (all, P<0.001). The overall FCRL1-6 prognostic signature was generated in the TCGA cohort (K-M, P<0.001; area under the curve (AUC), 0.649 for 3-year OS) and validated in the GSE65904 cohort (K-M, P<0.001; AUC, 0.659 for 3-year OS). The GSEA results revealed that high expression of FCRLs indicated activated immune-associated pathways, and FCRLs are positively associated with the infiltration of B cells. Conclusion. Highly expressed FCRLs were observed associated with a favourable OS of CM. FCRL1-6-based prediction signature could act as a biomarker to predict the prognosis of patients with CM.

In order to effectively remove mercury from raw natural gas, a preparation method of columnar sulfur-impregnated activated petroleum coke was proposed and mercury adsorption experiments were conduc...

The present work aims to evaluate the clinical efficacy and safety of low-intensity extracorporeal shock wave therapy (Li-ESWT) on patients with prostatitis-like symptoms (PLS). Patients with PLS were recruited and received four-week Li-ESWT (once per week), which was conducted at a frequency of 3 Hz with a preferred energy flow density of 0.25 mJ/mm2 . The scores of the National Institute of Health Chronic Prostatitis Symptoms Index (NIH-CPSI), International Prostate Symptom Score (IPSS), International Index of Erectile Function (IIEF-5), and Visual Analogue Scale (VAS) were recorded to assess the remission of disease in the 0, 1st, 2nd, 3rd, 4th, 5th, 8th and 16th weeks. A decrease of the NIH-CPSI score ≥6 was regarded as the effectiveness standard of Li-ESWT. Among 91 enrolled patients, the scores of all validated questionnaires presented significant improvements in the 4th week (p < .05) compared with that in baseline, except for IIEF-5. The treatment effective rates in the 1st, 2nd, 3rd, 4th, 5th, 8th and 16th weeks were 28.57%, 38.46%, 47.25%, 51.65%, 57.30%, 68.18% and 69.44%, respectively. No pronounced undesirable side effect has occurred. Li-ESWT is effective and safe in treating PLS. The efficacy can be maintained within three months.

BackgroundHepatitis B virus (HBV), the main risk factor for hepatocellular carcinoma (HCC) development, integrates into the host genome, causing genetic instability, which may trigger malignancies to exhibit chronic DNA replication stress, providing exploitable therapeutic vulnerabilities. Therefore, customizing prognostication approach and expanding therapeutic options are of great clinical significance to HBV-associated HCCs.MethodsA robust machine-learning framework was designed to develop a DNA replication stress-related prognostic index (PIRS) based on 606 retrospectively collected HBV-associated HCC cases. Molecular profiles and drug response of HCC cell lines were leveraged to predict therapeutic targets and agents for patients with high mortality risk.ResultsCompared with established population-based predictors, PIRS manifested superior performance for prognostic prediction in HBV-associated HCCs. Lower PIRS tightly associated with higher expression of HBV oncoproteins, activated immune/metabolism pathways and higher likelihood of responding to immunotherapy; while higher PIRS showed co-occurrence manner with elevated Ki-67 progression marker and cancer stemness, and significantly enriched in DNA replication stress, cell cycle pathways, chromatin remodeling regulons, and presented an ‘immune-cold’ phenotype with unfavorable clinical outcome. Through large-scale in silico drug screening, four potential therapeutic targets (TOP2A, PRMT1, CSNK1D, and PPIH) and five agents including three topoisomerase inhibitors (teniposide, doxorubicin, and epirubicin) and two CDK inhibitors (JNJ-7706621 and PHA-793887) were identified for patients with high PIRS.ConclusionsOverall, PIRS holds potential to improve the population-based therapeutic strategies in HCC and sheds new insight to the clinical management for those HBV carriers; current analytic framework provides a roadmap for the rational clinical development of personalized treatment.

Tumors are closely related to the tumor microenvironment (TME). The complex interaction between tumor cells and the TME plays an indisputable role in tumor development. Tumor cells can affect the TME, promote tumor angiogenesis and induce immune tolerance by releasing cell signaling molecules. Immune cell infiltration (ICI) in the TME can affect the prognosis of patients with bladder cancer. However, the pattern of ICI of the TME in bladder cancer has not yet been elucidated. Herein, we identified three distinct ICI subtypes based on the TME immune infiltration pattern of 584 bladder cancer patients using the ESTIMATE and CIBERSORT algorithms. Then, we identified three gene clusters based on the differentially expressed genes (DEGs) between the three ICI subtypes. In addition, the ICI score was determined using single sample gene set enrichment analysis (ssGSEA). The results suggested that patients in the high ICI score subgroup had a favorable prognosis and higher expression of checkpoint-related and immune activity-related genes. The high ICI score subgroup was also linked to increased tumor mutation burden (TMB) and neoantigen burden. A cohort treated with anti-PD-L1 immunotherapy confirmed the therapeutic advantage and clinical benefit of patients with higher ICI scores. In the end, our study also shows that the ICI score represents an effective prognostic predictor for evaluating the response to immunotherapy. In conclusion, our study deepened the understanding of the TME, and it provides new ideas for improving patients’ response to immunotherapy and promoting individualized tumor immunotherapy in the future.

IL-1α is closely related to the development and metastasis of cancer, and its polymorphisms have been reported affecting the susceptibility of malignancy tumors, yet the conclusions are controversial. Present an overall meta-analysis was performed to reach more general findings. Relevant literature was searched from Google Scholar, Web of Science, PubMed, EMBASE, CNKI database and Wanfang database, and the association among polymorphism and cancer risk was appraised by counting ORs and 95% CIs of overall and stratification analysis. The date from 15,586 cases and 18,430 controls in 40 publications were enrolled. There is significantly upregulated risk leads by rs3783553 in all genetic models, while the same tendency was found in all cancer types. The results also suggest a high risk of cancer susceptibility in patients carried rs1800587 polymorphism, of which draw out form allelic and homozygote models in overall studies, especially for cervical cancer. However, there are no significant results in analysis of rs17561. In a word, IL1A SNPs play an essential role in upregulating cancer susceptibility, and current analysis provides detail date for further study in the future.

Prostate cancer (PCa), a severe health burden for males, accounts for the second frequent cancer and fifth tumor specific death cancer around the world. Several studies on tumor‐infiltrating immune cells (TIICs) have shown inconsistent and controversial results to PCa. We downloaded a gene expression matrix and clinical information from TCGA, and CIBERSORT was used to identify the proportion of TIICs. Wilcoxon's Sign Rank Test evaluated different gene expression levels in PCa and normal tissues. Kaplan‐Meier curves were used to evaluate the associations of TIICs and recurrence‐free survival (RFS). Finally, based on the preset P‐value of .05, the distribution of TIICs in 73 PCa tissues and 11 normal tissues was illustrated. Activated CD4+ T cells and M0 macrophages account for a high proportion in PCa tissues, while neutrophils and monocytes were found at a high density in normal tissues. Further results showed that the density of plasma cells, Treg cells and resting mast cells were associated with advanced PCa. Additionally, M2 macrophages affected the RFS of PCa patients, and AR was also involved. In the current study, we first evaluated the immune infiltration among PCa and revealed that M2 macrophages could predict the prognosis of PCa patients. Meanwhile, based on the LASSO regression analysis, we established a novel nomogram to assess the recurrence risk of PCa based on immune cell proportions and clinical features.

Background As an integral membrane, Caveolin-1 (CAV1), is a pivotal component to make up the caveolae protein. It has been demonstrated to influence tumorigenicity, including bladder, colon, liver, stomach, breast and lung cancer. Several publications had illustrated the relationship of between CAV1 polymorphism and urinary cancer, but the results were not consistent. We performed a comprehensive meta-analysis to explore the associations and remove the fog. Material and methods Extensive retrieve was performed in PubMed, Embase, Medline, Web of Science, CNKI, and Wanfang database up to September, 2018. Odds ratios (ORs) and 95% confidence intervals (CIs) were conducted to evaluate the overall strength of the associations in five genetic models, as well as in subgroup analyses, stratified by ethnicity, cancer type or source of control. Q-test, Egger's test and Begg's funnel plot were applied to evaluate the heterogeneity and publication bias. In-silico analysis was managed to demonstrate the relationship of polymorphism and CAV1 mRNA expression level. Results 34 case-control studies with a total of 13,778 cancer cases and 20,581 healthy controls were enrolled into the meta-analysis. The polled result shown that an increased risk of rs1049334 polymorphism on urinary cancer were reveled in homozygote comparison model (MM vs. WW: OR = 1.240, 95% CI = 1.052-1.462, P = 0.011) and recessive comparison model (MM vs. MW + WW: OR = 1.198, 95% CI = 1.018-1.410, P = 0.030). What's more, rs17878467 polymorphism may play a protect role in the tumorigenesis of urinary cancer, shown in heterozygote comparison model (MW vs. WW: OR = 0.882, 95% CI = 0.78-0.999, P = 0.048). For rs7804372, the overall pooled results revealed a reducing risk in allelic contrast model (M vs. W: OR = 0.734, 95%CI = 0.544-0.99, P = 0.043), homozygote comparison model (MM vs. WW: OR = 0.532, 95% CI = 0.313-0.905, P = 0.020) and recessive comparison model (MM vs. MW + WW: OR = 0.580, 95% CI = 0.437-0.77, P 0.001). In the stratified analyses by cancer types, the risk of PCa is downgrade by rs7804372 in all five genetic models. The GTEx in-silico analysis index that the polymorphism of CAV1 influence its mRNA expression by a dose-dependent effective of its mutant allele. Conclusion rs1049334 polymorphismof CAV1 upgrade the risk of urinary cancer, while rs1049337 and rs7804372 polymorphisms may act as a protector of urinary cancer. Further large and well-designed studies in various populations are needed to confirm the results.

Background Hyaluronan (HA), an extracellular matrix component, accumulates in most chronic inflammatory tissues. Here, we studied the impact of HA on the pathogenesis of chronic prostatitis. Materials and methods First, we sorted demographic characteristics and peripheral blood serum samples from patients with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) to assess the relationship between the levels of HA in peripheral blood serum and the severity of inflammation in patients. Second, we induced an experimental autoimmune prostatitis (EAP) mouse model and treated the mice with 4-methylumbelliferone (4-MU) (200 mg/kg/day). After the mice were sacrificed, RNA from Th1 cells of the mouse spleens was extracted for RNA sequencing. We used weighted gene co-expression network analysis (WGCNA) to identify co-expressed gene modules and hub-gene related to the pathogenesis of EAP. The expression of critical genes associated with the identified pathway was confirmed by using western blot analysis. Results HA was significantly more highly expressed in CP/CPPS patients than in healthy volunteers and positively correlated with the severity of pain, urination symptoms, and quality of life. Besides, the protein expression of HA was significantly higher in prostate tissues derived from EAP models than in those derived from controls. 4-MU, an oral inhibitor of HA synthesis, relieved immunocyte infiltration to the prostate and significantly reduced the proportion of Th1 cells. Based on the WGCNA, we identified 18 co-expression modules and identified that the Grey60 and brown modules were positively associated with the EAP and negatively associated with the Control and 4-MU-treated groups. Pathway enrichment analyses and western blot assays proved that HA potentially activated the cell cycle pathway, increasing the proportion of Th1 cells promoting chronic prostatitis pathogenesis, while these processes were reversed by 4-MU treatment. Conclusions Our results suggest that HA is elevated in patients with CP/CPPS compared with healthy controls and that targeting HA through 4-MU suppresses the activity of the cell cycle-related pathway, potentially by decreasing the proportion of Th1 cells and relieving chronic prostatitis. Our findings might inspire the clinical treatment of chronic prostatitis.

The molecular classification of muscle-invasive bladder cancer (MIBC) based on transcriptomic signatures has been extensively studied. The complementary nature of information provided by different molecular profiles motivated us to refine MIBC classification by aggregating multi-omics data. We generated a consensus ensemble through ten multi-omics integrative clustering approaches on 396 MIBCs from TCGA. A total of 701 MIBCs from different sequencing technologies were used for external validation. Associations between subtypes and prognosis, molecular profiles, the tumour microenvironment, and potential response to frontline therapies were further analyzed. Nearest template prediction and random forest classification were used to develop a predictive signature/classifier for MIBC refinement. We identified four integrative consensus subtypes of MIBC, which were further designated basal-inflamed, basal-noninflamed, luminal-excluded and luminal-desert by immune profiling. Of note, the refinement of basal-like MIBC classification adds to the literature by identifying a basal-noninflamed MIBC subtype presenting with a significantly poor outcome and a global immune-cold phenotype, which might be triggered by Chr4 deletion and high activation of the oncogenic NRF2 pathway. In contrast, basal-inflamed MIBC showed high immunocyte infiltration and high expression of potential targets for immunotherapy. Using an external metastatic MIBC cohort in which patients received anti-PD-L1 treatment, we suggested that basal-inflamed MIBC had a higher likelihood of responding to immunotherapy than other MIBCs. The R package “refineMIBC” was offered as a research tool to refine MIBC from a single-sample perspective (https://github.com/xlucpu/refineMIBC). This consensus ensemble refines the intrinsic MIBC subtypes, which provides a blueprint for the clinical development of rational targeted and immunotherapeutic strategies.

Immunotherapy is a potential way to save the lives of patients with bladder cancer, but it only benefits approximately 20% of them. A total of 4,028 bladder cancer patients were collected for this study. Unsupervised non-negative matrix factorization and the nearest template prediction algorithms were employed for the classification. We identified the immune and non-immune classes from The Cancer Genome Atlas Bladder Urothelial Carcinoma (TCGA-BLCA) training cohort. The 150 most differentially expressed genes between these two classes were extracted, and the classification reappeared in 20 validation cohorts. For the activated and exhausted subgroups, a stromal activation signature was assessed by the NTP algorithm. Patients in the immune class showed highly enriched signatures of immunocytes, while the exhausted subgroup also exhibited activated transforming growth factor (TGF)-β1, and cancer-associated extracellular matrix signatures. Patients in the immune-activated subgroup showed a lower genetic alteration and better overall survival. Anti-PD-1/PD-L1 immunotherapy was more beneficial for the immune-activated subgroup, while immune checkpoint blockade therapy plus a TGF-β inhibitor or an EP300 inhibitor might achieve greater efficacy for patients in the immune-exhausted subgroup. Novel immune molecular classifier was identified for the innovative immunotherapy of patients with bladder cancer., Graphical Abstract, The selection of specific patients who can benefit from immunotherapy is critical for clinical application. Our study identifies a novel immune molecular classifier that provides innovative insights into immunotherapeutic strategies for bladder cancer patients. Patients in the immune-activated subgroup could be more susceptible to anti-PD-1/PD-L1 agents.

It is currently difficult for pathologists to diagnose pancreatic cancer (PC) using biopsy specimens because samples may have been from an incorrect site or contain an insufficient amount of tissue. Thus, there is a need to develop a platform-independent molecular classifier that accurately distinguishes benign pancreatic lesions from PC. Here, we developed a robust qualitative messenger RNA signature based on within-sample relative expression orderings (REOs) of genes to discriminate both PC tissues and cancer-adjacent normal tissues from non-PC pancreatitis and healthy pancreatic tissues. A signature comprising 12 gene pairs and 17 genes was built in the training datasets and validated in microarray and RNA-sequencing datasets from biopsy samples and surgically resected samples. Analysis of 1,007 PC tissues and 257 non-tumor samples from nine databases indicated that the geometric mean of sensitivity and specificity was 96.7%, and the area under receiver operating characteristic curve was 0.978 (95% confidence interval, 0.947-0.994). For 20 specimens obtained from endoscopic biopsy, the signature had a diagnostic accuracy of 100%. The REO-based signature described here can aid in the molecular diagnosis of PC and may facilitate objective differentiation between benign and malignant pancreatic lesions.

BackgroundBladder cancer is composed by a mass of heterogenetic characteristics, immunotherapy is a potential way to save the life of bladder cancer patients, but only benefit to about 20% patients.Methods and materialsA total of 4003 bladder cancer patients from 19 cohorts was enrolled in this study, collecting the clinical information and mRNA expression profile. The unsupervised non-negative matrix factorization (NMF) and nearest template prediction (NTP) algorithm was used to divide the patients to immune activated, immune exhausted and non-immune class. Verified gene sets of signatures were used to illustrate the characteristic of immunophenotypes. Clinical and genetic features were compared in different immunophenotypes.ResultsWe identified the immune class and non-immune classes in from TCGA-BLCA cohort. The 150 top different expression genes between these two classes was extracted as the input profile for the reappearing of the classification in the other 19 cohorts. As to the activated and exhausted subgroups, a stromal activation signature was conducted by NTP algorithm. Patients in the immune classes shown the highly enriched signatures of immunocytes, while the exhausted subgroup also shown an increased signature of TITR, WNT/TGF-β, TGF-β1 activated, and C-ECM signatures. Patients in the immune activated shown a lower CNA burden, better overall survival, and favorable response to anti-PD-1 therapy.ConclusionWe defined and validated a novel classifier among the 4003 bladder cancer patients. Anti-PD-1 immunotherapy could benefit more for the patients belong to immune activated subgroup, while ICB therapy plus TGF-β inhibitor or EP300 inhibitor might be more effectiveness for patients in immune exhausted subgroup.

The heterogeneity of the immune microenvironment leads to different responses in immune checkpoint blockade therapy. We aimed to propose a robust molecular classification system to investigate the relevance of the immune microenvironment subtype and prognosis of prostate cancer patients, as well as the therapeutic response to immune checkpoint blockade therapy. A total of 1,557 prostate cancer patients were enrolled, including 69 real‐world samples from our institute (titled the AHMU‐PC cohort). The non‐negative matrix factorization algorithm was employed to virtually microdissect patients. The immune enrichment was characterized by a high enrichment of T cell‐, B cell‐, NK cell‐, and macrophage‐associated signatures, by which patients were subclassified into nonimmune and immune classes. Subsequently, the immune class was dichotomized into immune‐activated and immune‐suppressed subtypes based on the stromal signature, represented by the activation of WNT/TGF‐β, TGF‐β1, and C‐ECM signatures. Approximately 14.9% to 24.3% of patients belonged to the immune‐activated subtype, which was associated with favorable recurrence‐free survival outcomes. In addition, patients in the immune‐activated subtype were predicted to benefit more from anti‐PD‐1/PD‐L1 therapy. In conclusion, our study identifies a novel immune molecular classifier that is closely related to clinical prognosis and provides novel insights into immunotherapeutic strategies for prostate cancer patients., This study identifies a novel immune molecular classifier for prostate cancer based on the analysis of 1,557 cases. Patients in the immune activated subgroup were associated with favorable prognosis and better outcomes of anti‐PD‐1/PD‐L1 therapy. Our findings suggest that the immune response drives clinical outcomes in prostate cancer, highlighting important implications for immunotherapy in patients with prostate cancer.

Cumulative evidence suggests that abnormal differentiation of T lymphocytes influences the pathogenesis of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). Thus, understanding the immune activation landscape of CP/CPPS would be helpful for improving therapeutic strategies. Here, we utilized BD™ AbSeq to digitally quantify both the protein and mRNA expression levels in single peripheral blood T cells from two CP/CPPS patients and two healthy controls. We utilized an integrated strategy based on canonical correlation analysis of 10 000+ AbSeq profiles and identified fifteen unique T‐cell subpopulations. Notably, we found that the proportion of cluster 0 in the CP/CPPS group (30.35%) was significantly increased compared with the proportion in the healthy control group (9.38%); cluster 0 was defined as effector T cells based on differentially expressed genes/proteins. Flow cytometry assays confirmed that the proportions of effector T‐cell subpopulations, particularly central memory T cells, T helper (Th)1, Th17 and Th22 cells, in the peripheral blood mononuclear cell populations of patients with CP/CPPS were significantly increased compared with those of healthy controls (P

INTRODUCTION AND OBJECTIVE:Bladder cancer (BCa) is the fourth most commonly occurring cancer in men and is the seventh leading cause of death from cancer among men and the eleventh among women in t...

Background Chronic prostatitis or chronic pelvic pain syndrome (CP/CPPS) is a disease with an unclear pathogenesis. Recent studies have reported that regulatory T (Treg) cells might be involved in the development of CP/CPPS. In this study we aimed to examine the functional role of Treg cells and explore the possible regulatory mechanism of Treg cells in CP/CPPS. Methods An experimental autoimmune prostatitis (EAP) mouse model was constructed; the numbers and functions of Treg cells in the EAP and control groups were tested. Then, cell differentiation experiments were conducted to evaluate the regulatory effect of autophagy on Treg cell differentiation. Furthermore, autologous CD4+ CD25- cells and CD4+ CD25+ cells from the two groups were magnetically sorted and cocultured to observe differences in cellular inhibitory functions. Finally, in an in vivo experiment, rapamycin was intraperitoneally injected into EAP mice for 4 weeks to observe the therapeutic effects. Results We found that the number and function of Treg cells in the EAP group were diminished compared to those in the control group. Meanwhile, the tolerance of pain in EAP mice had also decreased. Moreover, after using the autophagy activator rapamycin, the expression of the inflammatory cytokines interleukin-1β was decreased and the pain symptoms were alleviated. A mechanistic study found that autophagy activation promoted the differentiation of Treg and increased the suppressive functions of Treg cells, along with the elevated expression of GATA-3 and cytotoxic T lymphocyte antigen 4 (CTLA-4). Furthermore, in vivo administration of the autophagy activator rapamycin had similar effects on recovering the frequency and function of Treg cells as well as the expression of GATA-3 and CTLA-4. Conclusion The impaired frequency and function of Treg cells may contribute to the progression of CP/CPPS, and autophagy is a protective mechanism that promotes the differentiation of Treg cells and restores the suppressive functions of Treg cells. Autophagy may be a novel therapeutic option for patients with CP/CPPS.

BACKGROUND To facilitate early treatment, we constructed a nomogram to predict risk of postoperative fever before prostate biopsy in patients with high risk of fever. MATERIAL AND METHODS We collected information on patients undergoing prostate biopsy from January 2015 to December 2018 from their medical records, including clinical characteristics and laboratory test results. Finally, after strict screening, the prediction model was established in 440 patients who underwent a transrectal prostate biopsy (TRPB). We divided these patients into a training group and validation group at a ratio of 7: 3, respectively. Univariate analysis and multivariate logistic regression analysis were used to select the predictors and to develop the model. Calibration curve and C-index were used to evaluate the accuracy of the nomogram, while DCA was used to assess the clinical value. RESULTS The individualized predictive nomogram contained 3 clinical features - Biopsy-positive rate (BPR), Hematuria, and Urine WBC - significantly associated with post-biopsy fever. The nomogram had good discriminating ability in both the training group and validation group - the C-index was 0.774 (95% CI=0.717-0.832) in the training group and 0.808 (95% CI=0.706-0.909) in the validation group. Hosmer-Lemeshow test proved a good calibration curve fit. The DCA curve suggested that the nomogram would have good clinical utility. CONCLUSIONS This is the first study to develop a nomogram to predict fever after prostate biopsy via Biopsy-positive rate (BPR), Hematuria, and Urine WBC. Use of this nomogram might help prevent fever and infection, and could facilitate individualized medical treatment after prostate biopsy.

Aim: To explore the prognostic value of the cell division cycle-associated proteins (CDCA) family in clear cell renal cell carcinoma. Methods: Gene profiles were collected from the The Cancer Genome Atlas-Kidney Renal Clear Cell Carcinoma (TCGA-KIRC), the GSE29609 and GSE22541 datasets. Genetic alteration and DNA methylation data were downloaded from the cBioPortal and MethSurv. The functional enrichment data were analyzed by Metascape. Results: The mRNA expression of the CDCAs, except CBX2, was significantly increased in clear cell renal cell carcinoma patients. Genetic alterations might affect the expression of CDCAs, but promotor methylation does not affect CDCA gene expression. The overall expression of the CDCAs, according to the The Cancer Genome Atlas-KIRC database (hazard ratio [HR]: 2.18), the GSE29609 (HR: 6.08) and GSE22541 (HR: 6.73), was significantly associated with unfavorable overall survival. In addition, genes co-expressed with CDCAs (R2 ≥0.3) were highly associated with cell division and the FOXM1 pathway. Conclusion: Our study demonstrated that the aberrant expression of CDCA gene family members plays an indispensable role in tumorigenesis.

Understanding the immune activation landscape underlying the pathogenesis of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is helpful for improving therapeutic strategies. Here, we utilized BD™ AbSeq to digitally quantify both the protein and mRNA expression levels in single peripheral blood T cells from two CP/CPPS patients and two healthy controls. We utilized an integrated strategy based on canonical correlation analysis of 10,000+ AbSeq profiles and identified fifteen unique T-cell subpopulations. Notably, we found that the proportion of cluster 0 in the CP/CPPS group (30.35%) significantly increased compared with that in the healthy control group (9.38%), and cluster 0 was defined as effector T cells based on the differentially expressed genes/proteins. Consistently, flow cytometry assay confirmed that the proportions of effector T-cell subpopulations, particularly T helper (Th)1, Th17 and Th22 cells, in the peripheral blood mononuclear cell of patients with CP/CPPS were significantly increased compared with those healthy controls, indicating that aberration of effector T cells possibly leads to or intensifies CP/CPPS. Our results provide novel insights into the underlying mechanisms of CP/CPPS, which will benefit the treatment of CP/CPPS. Funding Statement: The National Natural Science Foundation of China (31430028, 81970597, 81630019, and 81870519); the presented research was financially supported by the National Science Foundation for Young Scientists (81802827), and the Scientific Research Foundation of the Institute for Translational Medicine of Anhui Province (2017ZHYX02) Declaration of Interests: All authors declared no competing interests. Ethics Approval Statement: The present study was approved by the ethics committee of the First Affiliated Hospital of Anhui Medical University. Patients were recruited from the out-patient department and controls were from heathy donators. Informed consent was obtained from the participants before experiments

Coal is the dominant energy source in China, and coal-fired power plant (CFPP) accounts for about half of coal consumption. However, air pollutant emissions from coal-fired power plants cause severe environmental and ecological problems. The most stringent regulations to limit air pollutant emissions from CFPP have been implemented in China since 2015. The ultra-low emission standards require that particulate matters (PMs) concentration from stack must not exceed 5 mg/Nm3. For exploring the emission characteristics of particulate matters and some trace elements, the field sampling test was carried out in a 660 MW ultra-low emission coal-fired power plant. It is equipped with low temperature economizer (LTE), electrostatic precipitators (ESP), wet flue gas desulfurization (WFGD), and wet electrostatic precipitator (WESP). The results showed that the mass removal efficiency of PM10 is about 80% in ESP and about 70% in WESP, in which most of them are PM2.5. The mass concentration removal efficiency of PM10 was 98.77% in ESP while that of PM2.5 is 98.58%. The mass concentration removal efficiency of PM10 was 63.43% in WESP while that of PM2.5 is 71.92%. At the same time, the trace elements on different particle sizes were analyzed. Manganese contents were found to be independent of the particle size. Cr, As and Pb are mainly enriched in the fine ash particles. In terms of the emission factors, Cr, As, Pb, and Mn are mainly in the fine particles.

Transporter associated with antigen processing protein (TAP) is a heterodimer protein consist of TAP1 and TAP2, act a pivotal part in the immune surveillance. In recent days, controversial relationships were reported between TAP polymorphisms and cancer risk, thus, a systematic meta-analysis was performed to resolve this discrepancy.We searched the PubMed, EMbase, Web of Science, CNKI and Wanfang databases, the cited references were also manually searched again, covering all the papers published until March 25, 2018. Quality assessment was conducted using the Newcastle-Ottawa Scale. All the meta-analysis was conducted with Stata version 12.0 software to assess the strength of the association.4719 cases and 4215 controls from 24 case-control studies related to TAP polymorphisms were enrolled. There was no significant association between TAP1-rs1135216, TAP1-rs4148873, TAP2-rs2228396, TAP2-rs241447 and TAP2-rs4148873 and cancer sensibility. Interestingly, a significant positive association was observed between TAP2 rs4148876 C/T polymorphism and increase cancer risk in homozygote and recessive models. Further in-silico results indicated the expression of TAP2 in cancer tissue is higher than that in normal tissue (cervical cancer, TPM = 70.2 vs. 24.0 respectively, P 0.01; acute myeloid leukemia, TPM = 52.5 vs. 8.8 respectively, P 0.01), and influence the survival time of acute myeloid leukemia patients (Log-rank P 0.05).Our finding suggested that TAP1-rs1135216, TAP1-rs4148873, TAP2-rs2228396, TAP2-rs241447 and TAP2-rs4148873 might not be involved in cancer risk, but the T allele of TAP2-rs4148876 might be a potential biomarker for judging cancer risk, and larger-scale studies are required to confirm our findings.

Background Currently, several studies have demonstrated that PRKAA1 polymorphisms conduce to the development of cancer. PRKAA1 gene encodes the AMP-activated protein kinase summit-α1, and plays an important role in cell metabolism. Thus, we performed a systematic review and meta-analysis of all enrolled eligible case-control studies to obtain a precise correlation between PRKAA1 polymorphism and cancer susceptibility. Methods Extensive retrieve was performed in Web of Science, Google Scholar, PubMed, EMbase, CNKI and Wanfang databases up to August 26, 2018. Odds ratios (ORs) and 95% CIs were performed to evaluate the overall strength of the associations in five models, as well as in subgroup analyses, stratified by ethnicity, cancer type or source of control. Q-test, Egger’s test and Begg’s funnel plot were applied to evaluate the heterogeneity and publication bias. In-silico analysis was performed to demonstrate the relationship of PRKAA1 expression correlated with cancer tissues and survival time. Results Twenty-two case-control studies from 14 publications were enrolled, with 17,068 cases and 20,871 controls for rs13361707, and 2514 cases and 3193 controls for rs10074991. Overall, we identified that the PRKAA1 rs13361707 polymorphism is not significantly associated with cancer susceptibility under all five genetic models. For rs10074991, we revealed a significant decrease risk in allelic comparison model (B vs. A: OR = 0.774, 95% CI = 0.642–0.931, PAdjust = 3.376*10− 2), heterozygote comparison model (BA vs. AA: OR = 0.779 95%CI = 0.691–0.877, PAdjust = 9.86*10− 10;), and dominant genetic model (BB + BA vs. AA: OR = 0.697 95%CI = 0.533–0.912, PAdjust = 4.211*10− 2;). Evidence from TCGA database and GTEx projects indicated that the expression of PRKAA1 in gastric cancer tissue is higher, compared to normal stomach tissue, as well as it in breast cancer and esophageal squamous cell carcinoma. However, the Kaplan-Meier estimate showed that there is no significant difference of OS and RFS between the low and high PRKAA1 TPM groups in gastric cancer, breast cancer, and esophageal carcinoma. Conclusions To sum up, PRKAA1 rs13361707 polymorphism is not participant with the increased risk of cancer, while the A allele of PRKAA1 rs10074991 revealed a significant decrease risk. Electronic supplementary material The online version of this article (10.1186/s12881-018-0704-8) contains supplementary material, which is available to authorized users.

BACKGROUND The aim of this study was to describe the clinical characteristics of Chinese ADPKD inpatients and to identify the factors associated with disease severity. MATERIAL AND METHODS We included 167 hospitalized patients (inpatients) with ADPKD in this study. Multiple regression analyses were conducted to determine factors correlated with estimated glomerular filtration rate (eGFR). Patients were stratified into subgroups according to the presence of symptoms, in which clinical parameters were analyzed and compared. RESULTS The mean age of hospitalized ADPKD patients was 48.7 years old, lumbar and/or abdominal pain was seen in 40.12% of patients, following by nephrolithiasis (38.92%), hematuria (30.54%), and urinary tract infection (24.55%). Serum thrombocyte level and hemoglobin exhibited significant positive correlations with eGFR. Symptomatic patients accounted for 71.26% of the studied population. Patients with hypertension had increased risk of presence of symptoms (OR=2.794, 95%CI=1.341-5.822). Low thrombocyte and hemoglobin levels were observed in patients with hematuria. CONCLUSIONS Thrombocyte level was positively correlated with eGFR but was not associated with presence of PKD-related symptoms, suggesting thrombocyte level might be an independent serum biomarker for disease progression. Hypertension was associated with increased risk of symptom occurrence, indicating the relationship between hypertension and disease progression. This study reveals the clinical characteristics of inpatients with ADPKD in China and provides clinicians with useful insights into this intractable disease.

Although translational research into autosomal dominant polycystic kidney disease (ADPKD) and its pathogenesis has made considerable progress, there is presently lack of standardized animal model for preclinical trials. In this study, we developed an orthologous mouse model of human ADPKD by cross‐mating Pkd2 conditional‐knockout mice (Pkd2 f3) to Cre transgenic mice in which Cre is driven by a spectrum of kidney‐related promoters. By systematically characterizing the mouse model, we found that Pkd2 f3/f3 mice with a Cre transgene driven by the mouse villin‐1 promoter (Vil‐Cre;Pkd2 f3/f3) develop overt cysts in the kidney, liver and pancreas and die of end‐stage renal disease (ESRD) at 4–6 months of age. To determine whether these Vil‐Cre;Pkd2 f3/f3 mice were suitable for preclinical trials, we treated the mice with the high‐dose mammalian target of rapamycin (mTOR) inhibitor rapamycin. High‐dose rapamycin significantly increased the lifespan, lowered the cystic index and kidney/body weight ratio and improved renal function in Vil‐Cre;Pkd2 f3/f3 mice in a time‐ and dose‐dependent manner. In addition, we further found that rapamycin arrested aberrant epithelial‐cell proliferation in the ADPKD kidney by down‐regulating the cell‐cycle‐associated cyclin‐dependent kinase 1 (CDK1) and cyclins, namely cyclin A, cyclin B, cyclin D1 and cyclin E, demonstrating a direct link between mTOR signalling changes and the polycystin‐2 dysfunction in cystogenesis. Our newly developed ADPKD model provides a practical platform for translating in vivo preclinical results into ADPKD therapies. The newly defined molecular mechanism by which rapamycin suppresses proliferation via inhibiting abnormally elevated CDK1 and cyclins offers clues to new molecular targets for ADPKD treatment.

At present, the overall genetic and epigenetic effects of Kruppel‐like factors (KLFs) on prostate cancer (PCa) remain unclear. Therefore, we systematically investigated the molecular differences in KLFs of transcription expression, promoter methylation and genetic alteration. Univariate and multivariate Cox proportional hazard regression was used to analyse the effect on RFS and establish the prognostic signature in the TCGA cohort, MSKCC and {"type":"entrez-geo","attrs":{"text":"GSE116918","term_id":"116918"}}GSE116918 cohorts employed to validate the signature. Biological pathway enrichment and the potential response to immunotherapy and chemotherapy were inferred. The transcription levels of most KLFs are associated with the clinical outcome of PCa. Gleason score (P = .009), pathology T stage (P = .006), KLF3 (P = .034), KLF5 (P = .002) and KLF7 (P = .035) were independent prognostic factors. A prognostic signature was established in the TCGA cohort (P

Background Ageing-associated molecular changes have been assumed to trigger malignant transformations and the epigenetic clock, and the DNA methylation age has been shown to be highly correlated with chronological age. However, the associations between the epigenetic clock and cervical squamous cell carcinoma (CSCC) prognosis, other molecular characteristics, and clinicopathological features have not been systematically investigated. To this end, we computed the DNA methylation (DNAm) age of 252 CSCC patients and 200 normal samples from TCGA and three external cohorts by using the Horvath clock model. We characterized the differences in human papillomavirus (HPV) 16/18 expression, pathway activity, genomic alteration, and chemosensitivity between two DNAm age subgroups. We then used Cox proportional hazards regression and restricted cubic spline (RCS) analysis to assess the prognostic value of epigenetic acceleration. Results DNAm age was significantly associated with chronological age, but it was differentiated between tumour and normal tissue (P < 0.001). Two DNAm age groups, i.e. DNAmAge-ACC and DNAmAge-DEC, were identified; the former had high expression of the E6/E7 oncoproteins of HPV16/18 (P < 0.05), an immunoactive phenotype (all FDRs < 0.05 in enrichment analysis), CpG island hypermethylation (P < 0.001), and lower mutation load (P = 0.011), including for TP53 (P = 0.002). When adjusted for chronological age and tumour stage, every 10-year increase in DNAm age was associated with a 12% decrease in fatality (HR 0.88, 95% CI 0.78–0.99, P = 0.03); DNAmAge-ACC had a 41% lower mortality risk and 47% lower progression rate than DNAmAge-DEC and was more likely to benefit from chemotherapy. RCS revealed a positive non-linear association between DNAm age and both mortality and progression risk (both, P < 0.05). Conclusions DNAm age is an independent predictor of CSCC prognosis. Better prognosis, overexpression of HPV E6/E7 oncoproteins, and higher enrichment of immune signatures were observed in DNAmAge-ACC tumours.

Several studies have reported a potential association between prostate volume (PV) and prostate disease. Here, we classified the risk factors for PV among benign prostatic hyperplasia (BPH) patients.In all, 4293 BPH patients with available clinical information were enrolled. Body mass index (BMI) was obtained as weight divided by height squared. PV was calculated as length × width × height (cm) × π/6. Mann-Whitney U tests were used to determine the differences between PV subgroups. Univariate and multiple linear regression tests were performed to uncover the connection between clinical features and PV. The differences in the age, BMI, height and fasting blood glucose (FBG) of the subgroups were evaluated by Kruskal-Wallis tests and adjusted with Bonferroni post hoc correction. A nomogram was created to directly illustrate the mutual interaction of amalgamator parameters.PV did not influence the incidence of kidney stones (P = .815), whereas prostate calculi were positively associated with an enlarged prostate (30 mL) (P .001). Age (adjusted R = 0.363, P .001), height (adjusted R = 0.088, P .001), BMI (adjusted R = 0.039, P = .013) and FBG (adjusted R = -0.034, P = .027) were the independent risk/protective factors related to enlarged PV among BPH patients. The nomogram illustrated the predictive risk of an enlarged prostate (30 mL) in men. The area under the ROC curve value was 0.659 in the training cohort and 0.677 in an internal validation cohort.Age, height and BMI were positive independent risk factors of enlarged PV in BPH patients, and FBG had a protective role.

PURPOSE Prostatic calculi (PCal) are commonly present with prostate disease; we aim to map the incidence and associated clinical risk factors of PCal in Han Chinese. MATERIAL AND METHODS We retrospectively selected men who sought a medical check-up in 2018. Basic clinical items, including age, weight, height, prostate specific antigen (PSA), uric acid (UA), fasting blood glucose (FBG), urinalysis results, and transabdominal prostate ultrasound, were recorded. Univariate and logistic regression analyses were performed to evaluate whether these factors were associated with the presence of PCal. RESULT We recorded the parameters of laboratory tests and clinical information from 14,427 men; men with PCal comprised 51.65% of the total group and 76.61% of the subgroup of benign prostate hyperplasia (BPH) patients. All the enrolled parameters showed meaningful differences, but the logistic regression analysis only indicated significant effects related to age (OR = 1.044, 95% CI = 1.040-1.047, and p

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a prevalent disease of the urogenital system. Alcohol has been reported to be closely related to CP/CPPS. Thus, we intended to verify the role of alcohol in CP/CPPS and determine the underlying mechanism.We induced experimental autoimmune prostatitis (EAP) mouse model by intradermally injecting a mixture of prostate antigens (PAgs) and complete Freund's adjuvant on days 0 and 28. Mice were treated with alcohol (control-alcohol and EAP-alcohol groups) or vehicle (control-vehicle, and EAP-vehicle groups) from day 32 to 42. Forty-two days after PAg injection, the pathological appearance of the prostate tissues was evaluated, and histological analyses of the prostate were performed. Chronic pelvic pain was assessed by applying von Frey filaments to the lower abdomen. Proinflammatory cytokines were detected by enzyme-linked immunosorbent assay tests. Then, we explored the effects of the NLRP3 inhibitor MCC950 on chronic pelvic pain and prostatic inflammation in this model.Histological analyses showed diffuse inflammation in the stromal tissues that were characterized by severe infiltration of neutrophils and mononuclear cells in mice in the EAP-alcohol group compared with EAP-vehicle group. Chronic pain tests showed that the response frequency was significantly increased using a von Frey filament at forces of 0.4, 1.0, and 4.0 g in EAP-alcohol group compared with EAP-vehicle (P .05). The levels of proinflammatory cytokines, including interferon (IFN)-γ, tumor necrosis factor (TNF)-α, IL-17, and IL-1β were all significantly elevated in EAP-alcohol group compared with the EAP-vehicle group (P .05). However, between the control-alcohol and control-vehicle groups, chronic pain tests, histological assays, and cytokine determinations showed no differences. Furthermore, our results demonstrated that MCC950 could decrease the expression level of NLRP3 inflammasome-related proteins including NLRP3, ASC, and caspase-1. The chronic pain tests, histological assays, and cytokine determinations showed that MCC950 could attenuate the chronic pain and prostatic inflammation through the inhibition of the NLRP3 inflammasome.This study indicated that alcohol could aggravate the severity of prostatic inflammation in EAP model though activating the NLRP3 inflammasome. Furthermore, the role of MCC950 in inhibiting NLRP3 inflammasome and decreasing IL-1β secretion to alleviate EAP severity may show that it is a promising therapeutic agent for CP/CPPS.

Background As one of the most common conditions in urological outpatients, chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) puzzles many individuals because of its unclear etiology and lack of effective treatment. Recently, immunological alterations underpinning CP/CPPS have been extensively investigated. Methods The PubMed, Web of Science, Cochrane library, and EMBASE databases were used to search original articles on immune mediators in patients with CP/CPPS and in experimental autoimmune prostatitis (EAP) models through April 10, 2020. Standardized mean differences (SMD) were calculated to summarize the differences in immune mediator levels between groups. Funnel plot, Begg’s funnel plot, Egger’s regression test, and the sensitivity analysis were applied to determine and visualize the stability of our findings. Results A total of 34 original studies were included in the meta-analysis, including 24 studies on patients with CP/CPPS and 10 studies on EAP models. We found that TNF-α, IL-1β, IL-6, and IL-8 were the four immune mediators that elevated in most of the samples derived from patients with CP/CPPS and the EAP models. The adjusted publication bias analysis indicated that publication bias was not existed, and the sensitivity analyses showed that the results were stable. Conclusions Immune responses play significant roles during the pathogenesis of CP/CPPS by promoting intraprostatic inflammation. Our findings provide potential diagnostic and therapeutic targets for CP/CPPS patients.

G4C14-A4T14 polymorphism of TP73 gene has been reported with a potential association in cancer risks through affected cell homeostasis; however the results were not consistent. We performed a comprehensive meta-analysis to explore the associations between G4C14-A4T14 polymorphism and cancer susceptibility. Extensive retrieve was performed in PubMed, EMBASE, Google Scholar, Web of Science, Wanfang database and CNKI database up to May 20, 2018. Odds ratios (ORs) and 95% confidence intervals (CIs) were conducted to evaluate the overall strength of the associations in five genetic models, as well as in subgroup analyses. Q-test, false-positive report probability analysis and trial sequential analysis, Egger’s test and Begg’s funnel plot were applied to evaluate the robustness of the results. In silico analysis was managed to demonstrate the relationship of TP73 expression correlated with cancer tissues. Finally, 36 case–control studies with a total of 9493 cancer cases and 13,157 healthy controls were enrolled into the meta-analysis. The pooled results present a significantly higher risk of G4C14-A4T14 polymorphism in all the five genetic models, as well as in the subgroups of Caucasian, cervical cancer, colorectal cancer, H-B subgroup and comfort to Hardy–Weinberg equilibrium subgroup. In silico analysis revealed that the expression of TP73 in cervical cancer tissue is higher than it in corresponding normal tissue, as well as in cervical cancer. All in all, TP73 G4C14-A4T14 polymorphism causes an upgrade cancer risk, especially in Caucasian population. G4C14-A4T14 polymorphism might be a potential biomarker for judging the tumorigenesis of cervical cancer and colorectal cancer.

Objective Matrix metalloproteinases 9 (MMP-9) is a zinc-dependent gelatinase, which could decrease the expression of extracellular matrix proteins and influence the metastatic behavior of tumors. In order to draw a comprehensive and precise result about the relationship of MMP-9 and urinary cancers, we presented the current meta-analysis. Methods We searched the PubMed, EMbase, Web of Science, CBM, CNKI and Wanfang databases, the cited references were also manually searched again, covering all the papers published until August 2018. Quality assessment was conducted using the Newcastle–Ottawa Scale. All the meta-analysis was conducted with Stata version 12.0 software to assess the strength of the association. Linkage disequilibrium (LD) analyses of gene polymorphisms and in-silico analysis of MMP-9 expression were also conducted to illustrate the relationship. Results 17 case-control studies comprise of more than 6154 cases and 6330 controls were enrolled and analyzed. After analyzed, we found that there is no significant association between rs3918241, rs2250889, rs17576 and rs17577 of MMP-9 and urinary cancers. LD analysis uncovered a significant LD between rs3918241 and rs17577 in CEU, CHBC CHBC ESN: r2 = 0.74; JPT: r2 = 0.77), as well as a remarkable LD between rs17576 and rs2250889 in CHBC JPT: r2 = 0.82). Furthermore, in-silico results indicated that the expression of MMP-9 in cancer tissue was higher than that in normal tissue in prostate cancer (Transcripts Per Kilobase Million (TPM) = 7.14 vs. 1.36, P Conclusions rs3918241, rs2250889, rs17576 and rs17577 polymorphisms of MMP-9 are not associated with altered risk of urinary cancer. More studies with large sample size focused on the combined effect of two or more polymorphisms of MMP-9 are necessary in the future.