Comprehensive analysis of N1-methylandenosine regulators and m1A-related mRNAs and lncRNAs as prognostic factors in bladder cancer.

Bladder cancer (BC) is a lethal malignancy and recurs frequently. m1A plays a vital role in maintaining the biological functions of non-coding RNAs. The Cancer Genome Atlas (TCGA) is a free website from where transcriptome data of BC were obtained. We chose m1A methylation regulators for this study. Six m1A methylation regulator genes have a higher expression in BC tissue compared to normal tissue. The aberrant expression of those m1A regulator genes was remarkably related to BC prognosis and clinicopathological features. First, m1A-related mRNAs and long noncoding RNAs (lncRNAs) were identified. Next, univariate Cox regression, least absolute shrinkage and selection operator (LASSO) Cox regression and multivariate Cox regression were performed to get the optimum RNAs for the development of prognostic signatures. Also, a nomogram with T status, lncRNA risk scores and mRNA risk scores was constructed. It revealed an adequate capacity to predict the overall survival of BC cases in the training set as well as in the testing set and in the total TCGA cohort. In conclusion, m1A methylation regulator genes played an important role in predicting the overall survival of BC patients. In addition, m1A-related lncRNAs and mRNAs illustrated underlying mechanisms of tumorigenesis and development of BC.

Fine particulate matter exposure exacerbated nasal mucosal damage in allergic rhinitis mice via NLRP3 mediated pyroptosis.

BACKGROUND: The incidence of nasal allergy/allergic rhinitis (AR) is rising worldwide, which has become a serious public health problem. Epidemiological studies point that exposure to environmental PM2.5 is closely linked to AR aggravation, however, the exactly mechanism is not clear. This study was performed to reveal molecular mechanisms of PM2.5 -induced AR deterioration. METHODS: Morphology and element analysis of PM2.5 was examined by scanning electron microscopy (SEM) and Energy Dispersive Spectrometer (EDS). A total of 24 female C57BL/6 mice were divided into three groups (control group, AR group, and PM2.5 + AR group, each group contains 8 mice). Mice from AR group and PM2.5 + AR group were intraperitoneally injected with OVA suspension (0.004% OVA+3% aluminum hydroxide) on days 1, 7, and 14. 0.2 mL /kg B.W. for sensitization; then the same mice were intranasal instilled with 5% OVA solution daily for 7 days to established AR mice model (each nostril for 10 µl, day 15-21). The mice were intranasal instilled PBS (control group and AR group, each nostril for 10 µl) or PM2.5 (AR + PM2.5 group, 4.0 mg/kg b.w., each nostril for 10 µl) at the same way from day 23-29. The nasal symptoms were evaluated after the last instillation of PM2.5. Pathological changes and ultrastructure of nasal mucosa were observed by HE staining and SEM. Goblet cells hyperplasia was performed by Periodic acid-Schiff (PAS) staining. NLRP3, Caspase-1, GSDMD and IL-1ß protein expression were assessed by immunohistochemical (IHC) staining. RESULTS: Exposure to PM2.5 aggravated rhinitis symptom, promoted the secretion of serum IgE level and destroyed ultrastructural of nasal mucosa. Interestingly, NLRP3, Caspase-1 GSDMD and IL-1ß protein expression were obviously elevated. NLRP3 /Capase-1/ GSDMD meditated cell pyroptosis participated in the process of AR exacerbation. However, macrophage is not the main effector cell. CONCLUSION: PM2.5 exposure induces aggravation of allergic rhinitis, which is related to NLRP3 inflammasome meditated caspase-1 activation and cell pyroptosis in nasal mucosal.

Corrigendum to "Construction of Protein-related Risk Score Model in Bladder Urothelial Carcinoma".

[This corrects the article DOI: 10.1155/2020/7147824.].

Reclassification of Kidney Clear Cell Carcinoma Based on Immune Cell Gene-Related DNA CpG Pairs.

BACKGROUND: A new method was developed based on the relative ranking of gene expression level, overcoming the flaw of the batch effect, and having reliable results in various studies. In the current study, we defined the two methylation sites as a pair. The methylation level in a specific sample was subject to pairwise comparison to calculate a score for each CpGs-pair. The score was defined as a CpGs-pair score. If the first immune-related CpG value was higher than the second one in a specific CpGs-pair, the output score of this immune-related CpGs-pair was 1; otherwise, the output score was 0. This study aimed to construct a new classification of Kidney Clear Cell Carcinoma (KIRC) based on DNA CpGs (methylation sites) pairs. METHODS: In this study, the biomarkers of 28 kinds of immune infiltration cells and corresponding methylation sites were acquired. The methylation data were compared between KIRC and normal tissue samples, and differentially methylated sites (DMSs) were obtained. Then, DNA CpGs-pairs were obtained according to the pairs of DMSs. In total, 441 DNA CpGs-pairs were utilized to construct a classification using unsupervised clustering analysis. We also analyzed the potential mechanism and therapy of different subtypes, and validated them in a testing set. RESULTS: The classification of KIRC contained three subgroups. The clinicopathological features were different across three subgroups. The distribution of immune cells, immune checkpoints and immune-related mechanisms were significantly different across the three clusters. The mutation and copy number variation (CNV) were also different. The clinicopathological features and potential mechanism in the testing dataset were consistent with those in the training set. CONCLUSIONS: Our findings provide a new accurate and stable classification for developing personalized treatments for the new specific subtypes.

A Methylation-Based Reclassification of Bladder Cancer Based on Immune Cell Genes.

BACKGROUND: Bladder cancer is highly related to immune cell infiltration. This study aimed to develop a new classification of BC molecular subtypes based on immune-cell-associated CpG sites. METHODS: The genes of 28 types of immune cells were obtained from previous studies. Then, methylation sites corresponding to immune-cell-associated genes were acquired. Differentially methylated sites (DMSs) were identified between normal samples and bladder cancer samples. Unsupervised clustering analysis of differentially methylated sites was performed to divide the sites into several subtypes. Then, the potential mechanism of different subtypes was explored. RESULTS: Bladder cancer patients were divided into three groups. The cluster 3 subtype had the best prognosis. Cluster 1 had the poorest prognosis. The distribution of immune cells, level of expression of checkpoints, stromal score, immune score, ESTIMATEScore, tumor purity, APC co_inhibition, APC co_stimulation, HLA, MHC class_I, Type I IFN Response, Type II IFN Response, and DNAss presented significant differences among the three subgroups. The distribution of genomic alterations was also different. CONCLUSIONS: The proposed classification was accurate and stable. BC patients could be divided into three subtypes based on the immune-cell-associated CpG sites. Specific biological signaling pathways, immune mechanisms, and genomic alterations were varied among the three subgroups. High-level immune infiltration was correlated with high-level methylation. The lower RNAss was associated with higher immune infiltration. The study of the intratumoral immune microenvironment may provide a new perspective for BC therapy.

Construction of Protein-related Risk Score Model in Bladder Urothelial Carcinoma.

BACKGROUND: Though there are several prognostic models, there is no protein-related prognostic model. The aim of this study is to identify possible prognostic-related proteins in bladder urothelial carcinoma and to try to predict the prognosis of bladder urothelial carcinoma based on these proteins. METHODS: Profile data and corresponding clinical traits were obtained from The Cancer Proteome Atlas (TCPA) and The Cancer Genome Atlas (TCGA) expression. Survival-associated protein in bladder urothelial carcinoma patients were estimated with Kaplan-Meier (KM) test and COX regression analysis. The potential molecular mechanisms and properties of these bladder urothelial carcinoma-specific proteins were also explored with the help of computational skills. The risk score model was validated in different clinical traits. Sankey diagram representation is for protein correlation. A new prognostic-related risk model based on proteins was developed by using multivariable COX analysis. Next, the alteration of the corresponding genes to the 6 prognostic-related proteins was analyzed. Finally, the relation between the corresponding genes and the immune infiltration was analyzed using the TIMER. RESULTS: Six proteins were identified to be associated with the prognosis of bladder urothelial carcinoma. A prognostic signature based on proteins (BECLIN, EGFR, PKCALPHA, SRC, ANNEXIN1, and AXL) performed moderately in prognostic predictions. The alteration of corresponding genes was in 31(24%) sequenced cases. ANXA1, AXL, and EGFR were positively related to CD8+ T cell. CONCLUSION: Our results screened six proteins of clinical significance. The importance of a personalized protein signature model in the recognition, surveillance. The abnormal expression of six prognostic-related proteins may be caused by corresponding gene alteration. Furthermore, these proteins may affect survival via the immune infiltration.

Retrograde intrarenal surgery in the management of symptomatic calyceal diverticular stones: a single center experience.

To evaluate the outcome of RIRS in managing symptomatic calyceal diverticular as a minimally invasive option, we retrospectively reviewed the records of 43 patients who underwent RIRS from 2005 to 2014 for symptomatic calyceal diverticular stones. A month after the initial operation, the success rate was (81.4%, 35 patients) of which 21 (48.83%) patients were stone free and 14 (32.6%) patients had clinically insignificant residual fragments (CIRFs), and 90% patients were symptom free. Eight patients (16.6%) had significant residual fragments (>3 mm), five of them became completely stone free after the second procedure, other three patients were symptom free and underwent a routine follow-up. The final treatment success rate was 93.0%. The initial success rate in the lower calyx was significantly lower than the other calices (P = 0.040). In addition, the association between the stone size and the initial treatment success was significant (P = 0.036). There was no association between any of our other variables and the success rate. The mean first operative time was 60.95 ± 12.43 min (range 34-92). No major complication (Clavien III-V) occurred, although there were five minor complications (11.6%) (Clavien I-II). There were no admissions to intensive care or deaths in our series, the mean hospitalization time was 1.77 ± 0.80 days. The management of calyceal diverticular calculus with RIRS is highly effective and can be accomplished with low morbidity.

Treatment of renal parapelvic cysts with a flexible ureteroscope.

PURPOSE: The aim of this study was to assess efficacy and safety of a flexible ureteroscope to treat renal parapelvic cysts. Treatment goals included avoidance of injury to renal vessels or hilar structure and minimizing the recurrence of cysts. PATIENTS AND METHODS: Renal parapelvic cysts from 15 patients that were incised and drained with a flexible ureteroscope were evaluated retrospectively between October 2011 and May 2013. Mean operation time, estimated blood loss and time of hospital stay were evaluated. Symptomatic and radiologic results, conducted by computed tomography or color Doppler ultrasound, were analyzed after surgery. RESULTS: According to the Dindo-Clavien classification, no major complications were observed during the different types of surgery. One patient exhibited red hematuria (mild), while bladder irritation symptoms (mild) occurred in three cases in the hospital and in two cases in the first postoperative month (moderate). Average total operation times, mean duration for the incision in the renal parapelvic cyst wall and mean estimated blood loss were 31 ± 8 min, 13 ± 2 min and 20 ± 5 ml, respectively. Mean hospital length of stay was 3 days. Radiologic success was defined as no recurrence of the cyst or a reduction in cyst size by at least half. In one case, cyst size did not reduce to half of the previous size, whereas cyst sizes were reduced to less than half of the previous size in four cases. No cysts were detected in the other cases after 6 or 12 months. CONCLUSIONS: Feasibility, safety and efficacy of the flexible ureteroscope for treatment of retrograde renal parapelvic cysts were demonstrated using appropriate patient selection and skilled surgical technique.

[Screening of membrane antigen differentially expressed in androgen-dependent prostate cancer and androgen-independent prostate cancer].

OBJECTIVE: To determine the screening of the expression of membrane proteins in androgen-dependent prostate cancer (ADPC) and androgen-independent prostate cancer (AIPC) and to explore the mechanism of membrane proteins in these two cancers. METHODS: Serum samples were collected from 3 patients with ADPC and another 3 patients with AIPC. The serum was incubated with ADPC cell line LNCaP and/or AIPC cell line PC-3 and detected by immunoprecipitation and Western blot. Differentially expressed proteins between ADPC and AIPC identified by mass spectrometry were compared and their expression level and location were analyzed by immunofluorescence. RESULTS: Altogether 11 membrane proteins were identifited, such as the Neural-Cadherin precursor, ER60 precursor, Claudin-4, and so on. Immunofluorescence revealed that the expression level of Claudin-4 in PC-3 cells was higher than in LNCaP cells. CONCLUSION: We can use the screening method to study membrane proteins in prostate cancer. Claudin-4 may play an important role in the pathogenesis and the development of AIPC.