Monetary policy as market stabilizer in the COVID-19 pandemic.

We categorize expansionary monetary policies based on interest rates, monetary easing, and liquidity decisions. We find that the stock market reacts positively to liquidity policy announcements by a more significant margin during and after the COVID-19 at market and industry levels compared with reactions to interest rate or monetary easing policy announcements. The economic consequences are large and persistent. Using firm characteristics as proxies for monetary policy transmission channels, we find that at firm level, the positive responses to liquidity policy announcements during the crisis are more pronounced for small and medium-sized businesses and non-state-owned enterprises relative to other enterprises.

MUC21 controls melanoma progression via regulating SLITRK5 and hedgehog signaling pathway.

Mucins are heavily glycosylated proteins secreted by various cell types, to protect the epithelial surface of the gastrointestinal tract from damage. Currently, increasing studies provided evidence to suggest that mucins play an essential role in regulating tumor progression. However, the role of mucins and the underpinning mechanism of how mucins drive melanoma progression remains elusive. In this study, we first demonstrated that mucin 21 (MUC21) expression was significantly upregulated in metastatic melanoma tissues, and a higher MUC21 expression resulted in poor overall survival in melanoma patients by The Cancer Genome Atlas database analysis. In vitro, MUC21 overexpression markedly promoted proliferative properties and aggressive behavior of melanoma cell A375 and A875, as assessed by Cell Counting Kit-8 and transwell assay. In mechanism, we proved that MUC21 suppressed expression of SLITRK5, an integral membrane protein, leading to activation of prosurvival hedgehog pathway and sustained melanoma development. More importantly, we found that combination of hedgehog pathway inhibitor cyclopamine and chemotherapy revealed an improved anticancer effect in MUC21 overexpression xenograft model. Altogether, our study described a novel role of MUC21 in regulating tumor progression, which offers a promising target for melanoma diagnosis and therapy.

Activation of BDNF/TrkB pathway promotes prostate cancer progression via induction of epithelial-mesenchymal transition and anoikis resistance.

Prostate cancer (PCa) is one of the most common malignant diseases in male worldwide, yet, the molecular mechanisms involved in PCa progression are still poorly understood. This study aimed to investigate the roles of the brain-derived neurotrophic factor/tropomyosin receptor kinase B (BDNF/TrkB) pathway in PCa progression. It was demonstrated by immunohistochemical analysis that both BDNF and TrkB were overexpressed in PCa tissues and elevated TrkB expression was tightly related with lymph node metastasis and advanced stage of PCa. In vitro studies showed that stimulation with rhBDNF or overexpression of TrkB in PCa cells promoted cell migration, invasion, and anoikis resistance. Overexpression of TrkB also resulted in epithelial-mesenchymal transition (EMT)-like transformation in cell morphology, whereas RNA interference-mediated TrkB depletion caused reversion of EMT. Further investigation demonstrated that protein kinase B (AKT) was responsible for BDNF/TrkB signaling-induced pro-migratory and pro-invasive effects, EMT, and anoikis resistance. Finally, in vivo studies confirmed that enhanced TrkB expression facilitated tumor growth, whereas downregulation of TrkB suppressed tumor growth. Our findings illustrate that BDNF/TrkB pathway is crucial for PCa progression, which may provide a novel therapeutic strategy for the treatment of advanced PCa.

Tetraiodothyroacetic acid and transthyretin silencing inhibit pro-metastatic effect of L-thyroxin in anoikis-resistant prostate cancer cells through regulation of MAPK/ERK pathway.

UNLABELLED: Prostate cancer is one of the most common malignancies in adult males and metastasis is the leading cause of death cases without satisfactory treatment options. Anoikis-resistance and migration are crucial aspects for the metastasis of various human cancer cells including prostate cancer and L-thyroxin (T4) has been proved to play vital roles in tumor metastasis. The present study demonstrated that T4 promoted migration and depressed detachment-induced apoptosis in anoikis-resistant prostate cancer cells while tetraiodothyroacetic acid (tetrac), a competitive antagonist of T4 at integrin αvß3, reversed T4 induced effects through diminishing expressions of XIAP, MMP-2, VEGF together with inhibited activity of MAPK/ERK pathway. In addition, we illustrated that over-expression of transthyretin (TTR) was positively correlated to the progression and metastatic potential in prostate cancer. Similar to tetrac, TTR silencing also inverted T4 mediated bioeffects on anoikis-resistant PC-3 cells. The current study sheds light on novel therapeutic strategies for metastatic prostate cancer. IMPLICATIONS: This study identified novel compound and target for preventing metastasis in anoikis-resistant prostate cancer cells, which might offer potential therapeutic alternatives for advanced prostate cancer.

Oleanolic acid inhibits cell survival and proliferation of prostate cancer cells in vitro and in vivo through the PI3K/Akt pathway.

Oleanolic acid (OA) is a naturally occurring pentacyclic triterpenoid and possesses diverse pharmacological activities, including anti-cancer effects that have been confirmed in multiple types of human cancers. However, the potential effect of natural OA on human prostate cancer is still unclear. The present study aimed to explore whether and how OA exerted anti-cancer effects in prostate cancer. Our data showed that OA inhibited cell viability and proliferation, and promoted cell apoptosis and G0/G1 phase cell cycle arrest in prostate cancer PC-3, DU145, and LNCaP cells, in a dose-dependent manner. In addition, OA was found to regulate the expression levels of apoptosis-related and cell cycle-related proteins, as well as the activity of PI3K/Akt pathway, in a dose-dependent manner. Mechanistically, our data revealed that OA exerted anti-cancer effects in vitro in PC-3 and DU145 cells by repressing the PI3K/Akt pathway. In agreement, OA also suppressed the tumor growth of PC-3 cells in vivo via inhibition of the PI3K/Akt pathway. In conclusion, our findings demonstrate the anti-cancer properties of OA in prostate cancer cells, both in vitro and in vivo, and provide the experimental evidence for the use of OA as an adjuvant agent for prostate cancer patients.

Doxazosin oral intake therapy to relieve stent - related urinary symptoms and pain: a prospective, randomized, controlled study.

OBJECTIVE: To assess the impact of Doxazosin Oral Intake Therapy on urinary symptoms and pain in patients with indwelling ureteral stents Patients and Methods: A total of 239 patients with ureteral stone-related hydronephrosis who underwent a double-J stent insertion after ureteroscopic lithotripsy were enrolled. Patients were randomized to receive doxazosin cotrolled release 4 mg once daily for 4 weeks or matching placebo. Patients completed the brief-form Chinese version Ureteric Stent Symptom Questionnaire (USSQ) and quality of life (QoL) score 2 weeks and 4 weeks after stent placement and 4 weeks after stent withdrawal. The analgesic use was also recorded during the stenting period. RESULTS: Patients in Doxazosin Oral Intake Therapy group, in the first 2 weeks and second 2 weeks with the stent in situ, expressed significant lower daytime frequency (p=0.028 and p=0.038), nocturia (p=0.021 and p=0.008) and urgency (p=0.012 and p=0.014), respectively. Similarly, flank pain score, QoL score and analgesic use were also significant less in the stenting period. There was no significant difference in scores of urinary symptoms, pain and QoL during the post-stent period between two cohorts. CONCLUSIONS: Doxazosin Oral Intake Therapy reduced stent-related urinary symptoms, pain and the negative impact on QoL.

Long non-coding RNA ANRIL is up-regulated in bladder cancer and regulates bladder cancer cell proliferation and apoptosis through the intrinsic pathway.

Antisense non-coding RNA in the INK4 locus (ANRIL) is a member of long non-coding RNAs and has been reported to be dysregulated in several human cancers. However, the role of ANRIL in bladder cancer remains unclear. This present study aimed to investigate whether and how ANRIL involved in bladder cancer. Our results showed up-regulation of ANRIL in bladder cancer tissues versus the corresponding adjacent non-tumor tissues. To explore the specific mechanisms, ANRIL was silenced by small interfering RNA or short hairpin RNA transfection in human bladder cancer T24 and EJ cells. Knockdown of ANRIL repressed cell proliferation and increased cell apoptosis, along with decreased expression of Bcl-2 and increased expressions of Bax, cytoplasmic cytochrome c and Smac and cleaved caspase-9, caspase-3 and PARP. However, no change of cleaved caspase-8 level was observed. Furthermore, in vivo experiment confirmed that knockdown of ANRIL inhibited tumorigenic ability of EJ cells in nude mice. Meanwhile, in accordance with in vitro study, knockdown of ANRIL inhibited expression of Bcl-2 and up-regulated expressions of Bax and cleaved caspase-9, but did not affect cleaved caspase-8 level. In conclusion, we first report that ANRIL possibly serves as an oncogene in bladder cancer and regulates bladder cancer cell proliferation and apoptosis through the intrinsic apoptosis pathway.

Investigation on uniaxial compression and fracture damage mode of prefabricated parallel double-jointed red sandstone.

As a special type of joint fracture, the fracture evolution characteristics of parallel double joints have important engineering significance for the stability analysis of fractured rock mass. In this work, a new method for calculating stress intensity factor of parallel double-jointed fractures was importantly proposed. Physical uniaxial compression tests were carried out on parallel double jointed red sandstone filled with cement mortar under different geometric parameters, and the macroscopic mechanical properties and failure characteristics of red sandstone are deeply analyzed. The results show that the larger the connectivity rate is, the smaller the peak stress and strain are. The increase of connectivity rate will affect the change rate of transverse strain in the center of rock bridge. The closer the dip angle of the joint is, the lower the peak stress is and the shorter the failure time is. The damage mode of joint tip encroachment affects the lateral displacement of the rock bridge center, and the displacement is always close to the first damage section. The closer the joint tip is to the load, the easier the end-face penetrating cracks occur. The research content can provide basic support for guaranteeing the stability of underground engineering rock mass.

Intraperitoneal laparoscopic single-site lymph node dissection in modified supine position during laparoscopic radical nephroureterectomy.

Technique modifications that aim to improve ergonomics of the surgical procedure without repositioning the upper tract urothelial carcinoma patients remain a challenge to urologists. We offer a novel technique to perform intraperitoneal laparoscopic single-site radical nephroureterectomy and pelvic lymph nodes dissection/retroperitoneal lymph nodes dissection in a supine position. Our novel technique is feasible and offers a significant improvement in operative efficiency, particularly in patients with locally advanced disease.

[Application of one-stop diagnosis and treatment plan in percutaneous nephrolithotomy for patients with complex renal calculi].

OBJECTIVE: To evaluate the safety and efficacy of preoperative computed tomography urography (CTU) three-dimensional reconstruction, intraoperative radiology and ultrasound guidance followed by percutaneous nephrolithotomy (PCNL) in the treatment of complex renal calculi. METHODS: We summarized the clinical data of 210 patients with complex renal calculi treated at our hospital from December 2008 to December 2011 in this retrospective study. In the one-stop diagnosis and treatment group (n = 119), the optimal puncture approach was designed according to CTU imaging and three-dimensional reconstruction. Percutaneous track was established by ultrasound and radiology guided puncture. PCNL was performed with EMS system. The control group (n = 91) underwent PCNL without radiological guidance. The success rate of puncture, mean accessing time, mean operative duration, intraoperative volume of blood loss and stone-free rate after one operative session were observed. Post-operative follow-ups were conducted until June 2012. RESULTS: Compared to the control group, the one-stop diagnosis and treatment group showed a higher success rate of puncture [98.3% (117/119) vs 92.3% (84/91), P = 0.037], a shorter operative duration [97.8 ± 13.20 vs 110.0 ± 14.73 min, P = 0.043] and a higher stone-free rate after one operative session [92.4% (110/119) vs 83.5% (76/91), P = 0.037]. No significant difference was detected in the mean accessing time[15.3 ± 3.7 vs 13.9 ± 3.9 min, P = 0.398] or intraoperative volume of blood loss [195.8 ± 84.15 vs 263.3 ± 82.06 ml, P = 0.059]. No severe complications occurred. No recurrence of calculi was noted during the follow-up period. CONCLUSION: One-stop diagnosis and treatment plan (CTU 3-D reconstruction plus radiology, ultrasound guidance followed by PCNL) may identify the puncture path, improve the successful rate of puncture and stone-free rates and reduce the complications of PCNL.

Effects of whole-body vibration training with different frequencies on the balance ability of the older adults: a network meta-analysis.

Purpose: To compare the effects of whole-body vibration training (WBVT) with different frequencies on the balance ability of older adults. Methods: Randomized controlled trials (RCTs) on the WBVT interventions on balance ability in older adults were searched through PubMed, Web of Science, The Cochrane Library, ProQuest, Embase, Opengrey, China National Knowledge Infrastructure (CNKI), Wanfang, and China Science and Technology Journal Database (CSTJ) databases from the establishment of the database to August 2022, and all literature that met the PICOS (Participants, Intervention, Comparison, Outcomes, Study design) criteria were enrolled. Two reviewers screened and assessed the methodological quality of the included literature according to the physiotherapy evidence database (PEDro) scale criteria. Statistical analysis was performed using Stata 14.0 software after data extraction. Results: Twenty-five RCTs with a total of 1267 subjects were finally included. The results of the pairwise comparison of the Network Meta-analysis showed that the Timed Up and Go Test (TUGT) values of Low-frequency whole-body vibration training (LF-WBVT) was lower than the placebo and traditional rehabilitation groups, and the difference was statistically significant [WMD = -1.37, 95% CI (-2.53, -0.20)] [WMD = -1.84, 95% CI(-3.17,-0.51)]. The Five-repetition Sit-to-Stand Test (5STS) values of LF-WBVT, Medium-frequency whole-body vibration training (MF-WBVT), and High-frequency whole-body vibration training (HF-WBVT) were lower than the placebo and traditional rehabilitation groups, but none of them were statistically significant. In addition, the TUGT and 5STS values of HF-WBVT had a tendency to be lower than those of LF-WBVT and MF-WBVT, but neither of them was statistically different. The cumulative probability ranking results of both TUGT and 5STS showed that HF-WBVT was the best protocol. Conclusion: Current evidence shows that HF-WBVT may be the best protocol for improving balance in older adults. Due to the study's limitations, the conclusion obtained in this study still needs to be further confirmed by more high-quality studies. Systematic Review Registration: [https://www.crd.york.ac.uk/PROSPERO/], identifier [CRD42021250405].

Emergency treatment of testicular torsion and postoperative follow-up: a 71 case report.

This study presented our experience in the treatment of testicular torsion, which may help achieve early diagnosis and improve therapeutic effects. A retrospective analysis was conducted in 71 patients with testicular torsion who were treated in our hospital from October 2007 to April 2011. The age of the patients ranged from 16 days to 34 years. All the patients had unilateral testicular torsion, which took place on the left side in 43 cases and on the right side in 28 cases. The course of the disease varied between three hours to 30 days. Post-operative follow-up was conducted until October 2011. Items examined included signs and symptoms at their first clinical visit, ultrasound findings, treatment in emergency surgery, and post-operative follow-up. In this study, the 71 patients were diagnosed with testicular torsion by color Doppler sonography, 7 had testicular fixation, 63 patients received orchiectomy, while 1 patient did not undergo surgery due to pressure from family members. Post-operative follow-up showed that the one patient's testicle, which had been reserved, atrophied, while all the other survived. No recurrence was found during the follow-up visits. It is concluded that an early diagnosis and surgery is important in improving the survival rate of testicular torsion, and the diagnosis and treatment by the first attending clinician is of critical importance.

NXPH4 Promotes Gemcitabine Resistance in Bladder Cancer by Enhancing Reactive Oxygen Species and Glycolysis Activation through Modulating NDUFA4L2.

Bladder cancer is one of the most prevalent kinds of cancer worldwide, and resistance to gemcitabine is a major problem for patients. The pathogenesis of bladder cancer and mechanism of resistance to chemotherapy remain to be explored. Through bioinformatics analysis, we first found that NXPH4 was independently related to the prognosis of patients with bladder cancer. Through wound healing assays, transwell invasion assays, and plate clone formation assays, we found that NXPH4 promoted the proliferation, migration, and invasion of bladder cancer cells. The induced gemcitabine resistance cell line also showed a higher expression of NXPH4. A glycolytic activity assay demonstrated that the expression of NXPH4 was positively related to glycolysis. A higher level of reactive oxygen species caused by enhanced levels of NXPH4 was found in gemcitabine-resistant cell lines. NDUFA4L2, glycolysis, and reactive oxygen species were shown to be essential for NXPH4-regulated functions through rescue assays in cell lines. The roles of NXPH4-regulated glycolysis, gemcitabine resistance, and NDUFA4L2 were validated in vivo as well. Our results imply that NXPH4 contributes to the proliferation, migration, and invasion of bladder cancer by maintaining the stability of NDUFA4L2 and consequently activating reactive oxygen species and glycolysis.

Dry and wet experiments reveal the significant role of FUT11 in clear cell renal cell carcinoma.

BACKGROUND: Renal cancer is one of the most common urogenital tumors worldwide. Although numerous traditional and relatively new therapeutic strategies have been adopted for clear cell renal cell carcinoma (ccRCC) patients, their effects are not satisfactory enough for the improvement of patients. The pathogenesis and progression of ccRCC requires further investigations. METHODS: Using a series of bioinformatic analyses, the expression levels, clinical relevance, and prognostic potential of FUT11 as well as its correlations with immune cells in ccRCC were investigated. The mRNA and protein expression levels of FUT11 in renal cancer cell lines and human tissues were determined using quantitative real-time-polymerase chain reaction (RT-PCR) and Western blot analyses. MTT, colony formation, Edu, and wound healing assays were performed to explore the function of FUT11 in renal cancer cell lines. The immunohistochemical staining of human and mouse tissues was performed to reveal the correlations between the expression levels of FUT11 and the infiltration level of immune cell subtypes. Using mouse xenograft models, the role of FUT11 was further investigated in-vivo. RESULTS: The data mining and corresponding analyses indicated that the expression levels of FUT11 were elevated in renal cancer and independently correlated with the prognosis of ccRCC patients. The cibersort and ssGSEA algorithms revealed differential infiltration levels of immune cells between the patients with distinct expression levels of FUT11; these results were verified by the consequent human renal cancer tissues and animal models. The MTT, colony formation, EdU, and wound healing assays showed that the decreased expression level of FUT11 could promote the proliferation and migration of renal cancer cell lines. The animal models-based analysis showed similar results. CONCLUSIONS: In conclusion, this study identified a novel important molecule correlated with the prognosis of ccRCC patients and revealed its immune-related role and its function in the proliferation and migration of renal cancer cells. This study might provide a novel basis for the treatment of renal cancer.

Construction of cuproptosis-related gene signature to predict the prognosis and immunotherapy efficacy of patients with bladder cancer through bioinformatics analysis and experimental validation.

Background: A new form of cell death, copper-dependent cell death (termed cuproptosis), was illustrated in a recent scientific study. However, the biological function or prognostic value of cuproptosis regulators in bladder cancer (BLCA) remains unknown. Materials and Methods: Sequencing data obtained from BLCA samples in TCGA and GEO databases were preprocessed for analysis. Biological function and immune cell infiltration levels evaluated by gene set variation analysis (GSVA) were employed to calculate enrichment scores. Iteration least absolute shrinkage and selection operator (LASSO) and COX regression model were employed to select feature genes and construct a novel cuproptosis-related (CR) score signature. The genomics of drug sensitivity in cancer (GDSC) and tumor immune dysfunction and exclusion (TIDE) analysis were used to predict the chemotherapy and immunotherapy efficacy for BLCA patients. The relative expression of the genes involved in the signature was also verified by real-time quantitative PCR (qRT-PCR) in cell lines and tissues. Results: Expression abundance and the prognostic value of cuproptosis regulators proved that cuproptosis might play a vital part in the carcinogenesis of BLCA. GSVA revealed that cuproptosis regulators might be associated with metabolism and metastasis-related pathways such as TGF-ß, protein secretion, oxidative Phosphorylation, MYC targets, MTORC1, and adipogenesis pathways. CR scores could predict the prognosis and evaluate the chemotherapy and immunotherapy efficacies of BLCA. CR scores were positively correlated with EMT, MYC, MTORC1, HEDGEHOG, and E2F signaling pathways; meanwhile, they were negatively correlated with several immune cell infiltration levels such as CD8+ T cells, γδT cells, and activated dendritic cells. Several GEO datasets were used to validate the power of prognostic prediction, and a nomogram was also established for clinical use. The expressions of DDX10, RBM34, and RPL17 were significantly higher in BLCA cell lines and tissues in comparison with those in the corresponding normal controls. Conclusion: Cuproptosis might play an essential role in the progression of BLCA. CR scores could be helpful in the investigation of prognostic prediction and therapeutic efficacy and could make contributions to further studies in BLCA.

Mining the key genes for ventilator-induced lung injury using co-expression network analysis.

Mechanical ventilation is extensively adopted in general anesthesia and respiratory failure management, but it can also induce ventilator-induced lung injury (VILI). Therefore, it is of great urgency to explore the mechanisms involved in the VILI pathogenesis, which might contribute to its future prevention and treatment. Four microarray datasets from the GEO database were selected in our investigation, and were subjected to the Weighted Gene Co-Expression Network Analysis (WGCNA) to identify the VILI-correlated gene modules. The limma package in R software was used to identify the differentially expressed genes (DEGs) between the VILI and control groups. WGCNA was constructed by merging the GSE9314, GSE9368, GSE11434 and GSE11662 datasets. A total of 49 co-expression network modules were determined as associated with VILI. The intersected genes between hub genes screened from DEGs for VILI and those identified using WGCNA were as follows: Tlr2, Hmox1, Serpine1, Mmp9, Il6, Il1b, Ptgs2, Fos and Atf3, which were determined to be key genes for VILI. Those key genes were validated by GSE86229 and quantitative PCR (qPCR) experiment to have significantly statistical difference in their expression between the VILI and control groups. In a nutshell, nine key genes with expression differences in VILI were screened by WGCNA by integrating multiple datasets.

Identification of Survival and Therapeutic Response-Related Ferroptosis Regulators in Bladder Cancer through Data Mining and Experimental Validation.

Ferroptosis has been reported to regulate tumorigenesis, metastasis, drug resistance and the immune response. However, the potential roles of ferroptosis regulators in the advancement of bladder cancer remain to be explored. We systematically evaluated the multidimensional alteration landscape of ferroptosis regulators in bladder cancer and checked if their expression correlated with the ferroptosis index. We used least absolute shrinkage and selection operator regression to form a signature consisting of seven ferroptosis regulator. We confirmed the signature's prognostic and predictive accuracy with five independent datasets. A nomogram was built to predict the overall survival and risk of death of patients. The relative expression of the genes involved in the signature was also clarified by real-time quantitative PCR. We found the risk score was related to tumor progression and antitumor immunity-related pathways. Moreover, there existed negative association between the relative antitumor immune cell infiltration level and the risk score, and higher tumor mutation burden was found in the group of lower risk score. We used The Tumor Immune Dysfunction and Exclusion database and IMvigor210 cohort having immunotherapy efficacy results to confirm the prediction function of the risk score. Furthermore, the ferroptosis regulator signature could also reflect the chemotherapy sensitivity of bladder cancer.

Identification of novel biomarkers of prostate cancer through integrated analysis.

BACKGROUND: The current methods adopted to screen for prostate cancer (PCa) can sometimes be misleading and inaccurate. Moreover, for advanced stages of PCa, the current effect of treatment is not satisfactory for some patients. Accordingly, we aimed to identify new biomarkers for the diagnosis and prognosis of PCa. METHODS: A series of bioinformatic tools were utilized to search for potential new biomarkers of PCa and analyze their functions, expression, clinical relevance, prognostic value, and underlying mechanisms. RESULTS: Although ASPN was overexpressed in PCa, EDN3, PENK, MEIS2, IGF1, and CXCL12 were downregulated. The univariate Cox regression analysis showed that abnormally high expression of ASPN and low expression of other genes predicted worse prognosis. Moreover, the multivariate Cox regression analysis showed that ASPN, PENK, and MEIS2 were independently associated with the overall survival (OS) of patients, whereas other markers were not. The outcomes of gene ontology and gene set enrichment analysis showed that the expression levels of these genes might be associated with cell proliferation and infiltration of immune cells in PCa. CONCLUSIONS: We demonstrated that ASPN, EDN3, PENK, MEIS2, IGF1, and CXCL12 are possibly novel diagnostic indicators for PCa, whereas ASPN, PENK, and MEIS2 show appealing potential to predict the prognosis of this disease.

Scoring System Based on RNA Modification Writer-Related Genes to Predict Overall Survival and Therapeutic Response in Bladder Cancer.

Introduction: It's widely reported the "writer" enzymes mediated RNA adenosine modifications which is known as a crucial mechanism of epigenetic regulation in development of tumor and the immunologic response in many kinds of cancers. However, the potential roles of these writer genes in the progression of bladder cancer (BLCA) remain unclear. Materials and Methods: We comprehensively described the alterations of 26 RNA modification writer genes in BLCA from the genetic and transcriptional fields and identified writer-related genes from four independent datasets. Utilizing least absolute shrinkage and selection operator (LASSO) regression and multivariate Cox regression, we constructed a ten writer-related gene signature. After that, we confirmed the predictive and prognostic value of this signature on another six independent datasets and established a nomogram to forecast the overall survival (OS) and mortality odds of BLCA patients clinically. Results: The writer-related genes signature showed good performance in predicting the OS for BLCA patients. Moreover, the writer-related gene signature was related to EMT-related pathways and immune characteristics. Furthermore, the immune cell infiltration levels of CD8 T cells, cytotoxic cells, M1/2 macrophage cells and tumor mutation burden might be able to predict which patients will benefit from immunotherapy. This could also be reflected by the writer-related gene signature. Conclusions: This signature might play an important role in precision individualized immunotherapy. The present work highlights the crucial clinical implications of RNA modifications and may help developing individualized therapeutic strategies for patients with BLCA.

Comprehensive analysis of the functional and prognostic value of E2F transcription factors in human prostate cancer through data mining and experimental validation.

BACKGROUND: A growing body of evidence shows that E2F transcription factors play a significant role in the tumorigenesis of prostate cancer. However, their functional and prognostic value has not been fully illustrated. Therefore, we used bioinformatics methods to further analyze the possible roles of E2F transcription factors in the development and progression of prostate cancer. METHODS: We explored the expression levels of E2F transcription factors using data from The Cancer Genome Atlas (TCGA) and Oncomine database in paired and unpaired samples. The clinical correlation and prognostic value of E2F transcription factors were assessed. Using the R package "pROC", we judged the diagnostic value of E2F transcription factors. The online website tool cBioPortal was also employed to find possible gene alterations of E2F transcription factors in samples from TCGA. The R package "clusterprofiler" was used to conduct functional analysis. Moreover, we also used the Tumor Immune Estimation Resource to search for the associations between E2F transcription factors and the infiltration levels of 6 kinds of immune cells. Finally, quantitative real-time polymerase chain reaction (PCR) was conducted to validate the expression levels of E2F transcription factors in human paired prostate tissues. RESULTS: E2F1/2/3/5 messenger RNA (mRNA) expression levels were higher in prostate cancer tissues than in normal tissues, while E2F4 and E2F6 mRNA expression levels were lower (P<0.05). All E2F transcription factors were associated with clinical parameters. Kaplan-Meier analysis revealed that E2F1/4/6/8 were notably associated with the overall survival of patients with prostate cancer (P<0.05). Receiver operating characteristic (ROC) curve results showed that except for E2F7, the other E2F transcription factors had diagnostic value for prostate cancer (P<0.05). We further found close associations between E2F transcription factors and the infiltration levels of immune cells. The results of quantitative real-time PCR were consistent with those from public databases. CONCLUSIONS: E2F transcription factor family members are differentially expressed in prostate cancer and are significantly related to the prognosis of patients, suggesting that they may be adopted as biomarkers for prognosis prediction and the treatment of prostate cancer.