Histologic subtypes of non-muscle invasive bladder cancer

The majority of bladder cancers(BCs)are non-muscle invasive BCs(NMIBCs)and show the morphology of a conventional urothelial carcinoma(UC).Aberrant morphology is rare but can be observed.The classification and characterization of histologic subtypes(HS)in UC in BC have mainly been described in muscle in-vasive bladder cancer(MIBC).However,the currently used classification is ap-plied for invasive urothelial neoplasm and therefore,also valid for a subset of NMIBC.The standard transurethral diagnostic work-up misses the presence of HS in NMIBC in a considerable percentage of patients and the real prevalence is not known.HS in NMIBC are associated with an aggressive phenotype.Conse-quently,clinical guidelines categorize HS of NMIBC as“(very)high-risk”tumors and recommend offering radical cystectomy to these patients.Alternative strategies for bladder preservation can only be offered to highly selected patients and ideally within clinical trials.Novel treatment strategies and biomarkers have been established MIBC and NMIBC but have not been comprehensively invest-igated in the context of HS in NMIBC.Further evaluation prior to implementation into clinical practice is needed.

Cryoablation techniques in bladder cancer: A review

Bladder cancer(BC)ranks as the tenth most common cancer globally.Histopathologically,BC is broadly categorized into urothelial and non-urothelial BC.Urothelial carcinoma represents over 90%of BC in most regions worldwide.The standard treatment procedure for diagnosing and treating non-muscle-invasive bladder cancer(NMIBC)is transurethral resection of bladder tumors(TURBT).Currently,the standard of care for muscle-invasive bladder cancer(MIBC)is neoadjuvant chemotherapy followed by radical cystectomy.Cryoablation therapy is a medical technique that uses extremely low temperatures to destroy diseased tissue.This treatment serves as a therapeutic tool for both benign and malignant diseases in organs such as the kidney,prostate gland,lung,liver,and breast,and is particularly effective for unresectable tumors,offering less trauma,quick recovery,good tolerability,and symptom control.However,cryoablation has its limitations.Over the past few years,cryoablation therapy has emerged as a new method for treating early BC.This treatment is minimally invasive,precise,and offers quick recovery,providing patients with a new treatment option.Although randomized studies are still limited,increasing evidence suggests its potential application in bladder cancer combined with transurethral resection(TURBT)or medication.Cryoablation is not standard therapy for bladder cancer.Treatment decisions should be discussed by a multidisciplinary team of urologists,oncologists,and interventional physicians and require more randomized controlled trials to define patient selection criteria and treatment approaches.

Potential clinical application of microRNAs in bladder cancer

Bladder cancer(BC)is the tenth most prevalent malignancy globally,presenting significant clinical and societal challenges because of its high incidence,rapid progression,and frequent recurrence.Presently,cystoscopy and urine cytology serve as the established diagnostic methods for BC.However,their efficacy is limited by their invasive nature and low sensitivity.Therefore,the development of highly specific biomarkers and effective noninvasive detection strategies is imperative for achieving a precise and timely diagnosis of BC,as well as for facilitating an optimal tumor treatment and an improved prognosis.microRNAs(miRNAs),short noncoding RNA molecules spanning around 20–25 nucleotides,are implicated in the regulation of diverse carcinogenic pathways.Substantially altered miRNAs form robust functional regulatory networks that exert a notable influence on the tumorigenesis and progression of BC.Investigations into aberrant miRNAs derived from blood,urine,or extracellular vesicles indicate their potential roles as diagnostic biomarkers and prognostic indicators in BC,enabling miRNAs to monitor the progression and predict the recurrence of the disease.Simultaneously,the investigation centered on miRNA as a potential therapeutic agent presents a novel approach for the treatment of BC.This review comprehensively analyzes biological roles of miRNAs in tumorigenesis and progression,and systematically summarizes their potential as diagnostic and prognostic biomarkers,as well as therapeutic targets for BC.Additionally,we evaluate the progress made in laboratory techniques within this field and discuss the prospects.

TM9SF1 promotes bladder cancer cell growth and infiltration

BACKGROUND Bladder cancer(BC)is the most common urological tumor.It has a high recur-rence rate,displays tutor heterogeneity,and resists chemotherapy.Furthermore,the long-term survival rate of BC patients has remained unchanged for decades,which seriously affects the quality of patient survival.To improve the survival rate and prognosis of BC patients,it is necessary to explore the molecular mechanisms of BC development and progression and identify targets for treatment and intervention.Transmembrane 9 superfamily member 1(TM9SF1),also known as MP70 and HMP70,is a member of a family of nine transmembrane superfamily proteins,which was first identified in 1997.TM9SF1 can be expressed in BC,but its biological function and mechanism in BC are not clear.AIM To investigate the biological function and mechanism of TM9SF1 in BC.Overexpression of TM9SF1 increased the in vitro proliferation,migration,and invasion of BC cells by promoting the entry of BC cells into the G2/M phase.Silencing of TM9SF1 inhibited in vitro proliferation,migration,and invasion of BC cells and blocked BC cells in the G1 phase.CONCLUSION TM9SF1 may be an oncogene in BC.

Uncovering the epidemiology of bladder cancer in the Arab world: A review of risk factors, molecular mechanisms, and clinical features

Objective:Bladder cancer(BC)is a significant public health concern in the Middle East and North Africa,but the epidemiology and clinicopathology of the disease and contributors to high mortality in this region remain poorly understood.The aim of this systematic review was to investigate the epidemiological features of BC in the Arab world and compare them to those in Western countries in order to improve the management of this disease.Methods:An extensive electronic search of the PubMed/PMC and Cochrane Library databases was conducted to identify all articles published until May 2022,following the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines.A total of 95 articles were included in the final analysis after title,abstract,and full-text screening,with additional data obtained from the GLOBOCAN and WHO 2020 databases.

Metabolomics for the diagnosis of bladder cancer: A systematic review

Objective: Metabolomics has been extensively utilized in bladder cancer (BCa) research, employing mass spectrometry and nuclear magnetic resonance spectroscopy to compare various variables (tissues, serum, blood, and urine). This study aimed to identify potential biomarkers for early BCa diagnosis.Methods: A search strategy was designed to identify clinical trials, descriptive and analytical observational studies from databases such as Medline, Embase, Cochrane Central Register of Controlled Trials, and Latin American and Caribbean Literature in Health Sciences. Inclusion criteria comprised studies involving BCa tissue, serum, blood, or urine profiling using widely adopted metabolomics techniques like mass spectrometry and nuclear magnetic resonance. Primary outcomes included description of metabolites and metabolomics profiling in BCa patients and the association of metabolites and metabolomics profiling with BCa diagnosis compared to control patients. The risk of bias was assessed using the Quality Assessment of Studies of Diagnostic Accuracy.Results: The search strategy yielded 2832 studies, of which 30 case-control studies were included. Urine was predominantly used as the primary sample for metabolite identification. Risk of bias was often unclear inpatient selection, blinding of the index test, and reference standard assessment, but no applicability concerns were observed. Metabolites and metabolomics profiles associated with BCa diagnosis were identified in glucose, amino acids, nucleotides, lipids, and aldehydes metabolism.Conclusion: The identified metabolites in urine included citric acid, valine, tryptophan, taurine, aspartic acid, uridine, ribose, phosphocholine, and carnitine. Tissue samples exhibited elevated levels of lactic acid, amino acids, and lipids. Consistent findings across tissue, urine, and serum samples revealed downregulation of citric acid and upregulation of lactic acid, valine, tryptophan, taurine, glutamine, aspartic acid, uridine, ribose, and phosphocholine.

LncRNA MEG3 Inhibits the Epithelial-mesenchymal Transition of Bladder Cancer Cells through the Snail/E-cadherin Axis

Objective This study aimed to investigate the role of the long noncoding RNA(lncRNA)maternally expressed gene 3(MEG3)in the epithelial-mesenchymal transition(EMT)of bladder cancer cells and the potential mechanisms.Methods Cell invasion,migration,and wound healing assays were conducted to assess the effects of MEG3 on the invasive and migratory capabilities of bladder cancer cells.The expression levels of E-cadherin were measured using Western blotting,RT-qPCR,and dual luciferase reporter assays.RNA immunoprecipitation and pull-down assays were performed to investigate the interactions between MEG3 and its downstream targets.Results MEG3 suppressed the invasion and migration of bladder cancer cells and modulated the transcription of E-cadherin.The binding of MEG3 to the zinc finger region of the transcription factor Snail prevented its ability to transcriptionally repress E-cadherin.Additionally,MEG3 suppressed the phosphorylation of extracellular regulated protein kinase(ERK),c-Jun N-terminal kinase(JNK),and P38,thereby decreasing the expression of Snail and stimulating the expression of E-cadherin.Conclusion MEG3 plays a vital role in suppressing the EMT in bladder cancer cells,indicating its potential as a promising therapeutic target for the treatment of bladder cancer.

Current and Potential Roles of Ferroptosis in Bladder Cancer

Ferroptosis,a type of regulated cell death driven by iron-dependent lipid peroxidation,is mainly initiated by extramitochondrial lipid peroxidation due to the accumulation of iron-dependent reactive oxygen species.Ferroptosis is a prevalent and primitive form of cell death.Numerous cellular metabolic processes regulate ferroptosis,including redox homeostasis,iron regulation,mitochondrial activity,amino acid metabolism,lipid metabolism,and various disease-related signaling pathways.Ferroptosis plays a pivotal role in cancer therapy,particularly in the eradication of aggressive malignancies resistant to conventional treatments.Multiple studies have explored the connection between ferroptosis and bladder cancer,focusing on its incidence and treatment outcomes.Several biomolecules and tumor-associated signaling pathways,such as p53,heat shock protein 1,nuclear receptor coactivator 4,RAS-RAF-MEK,phosphatidylinositol 3-kinase-AKT-mammalian target of rapamycin,and the Hippo-tafazzin signaling system,exert a moderating influence on ferroptosis in bladder cancer.Ferroptosis inducers,including erastin,artemisinin,conjugated polymer nanoparticles,and quinazolinyl-arylurea derivatives,hold promise for enhancing the effectiveness of conventional anticancer medications in bladder cancer treatment.Combining conventional therapeutic drugs and treatment methods related to ferroptosis offers a promising approach for the treatment of bladder cancer.In this review,we analyze the research on ferroptosis to augment the efficacy of bladder cancer treatment.

Clinical implications of single cell sequencing for bladder cancer

Bladder cancer(BC)is the 10th most common cancer worldwide,with about 0.5 million reported new cases and about 0.2 million deaths per year.In this scoping review,we summarize the current evidence regarding the clinical implications of single-cell sequencing for bladder cancer based on PRISMA guidelines.We searched PubMed,CENTRAL,Embase,and supplemented with manual searches through the Scopus,and Web of Science for published studies until February 2023.We included original studies that used at least one single-cell technology to study bladder cancer.Forty-one publications were included in the review.Twenty-nine studies showed that this technology can identify cell subtypes in the tumor microenvironment that may predict prognosis or response to immune checkpoint inhibition therapy.Two studies were able to diagnose BC by identifying neoplastic cells through single-cell sequencing urine samples.The remaining studies were mainly a preclinical exploration of tumor microenvironment at single cell level.Single-cell sequencing technology can discriminate heterogeneity in bladder tumor cells and determine the key molecular properties that can lead to the discovery of novel perspectives on cancer management.This nascent tool can advance the early diagnosis,prognosis judgment,and targeted therapy of bladder cancer.

Inhibition of proliferation,migration,and invasiveness of bladder cancer cells through SAPCD2 knockdown

Introduction:Bladder cancer(BC)has a high incidence and mortality rate worldwide.Suppressor anaphasepromoting complex domain containing 2(SAPCDC2)is over-expressed in a variety of tumors.Objectives:This study investigated the effects of SAPCD2 knockdown on BC cells.Methods:T24 and UMUC3 cell models and the xenografted BC tumor model with SAPCD2 knockdown were established to observe the malignant phenotype of BC cells by cell counting kit-8 assay,colony formation test,wound healing,and Transwell assay,mRNA and proteins expressions were measured with quantitative real-time polymerase chain reaction,western blotting,and tissue immunohistochemistry.Lithium chloride agonist on the Wnt/β-catenin pathway was used to clarify the molecular mechanism of SAPCD2 knockdown.Results:SAPCD2 expression was significantly higher in BC cell lines than in SVHUC-1 cells.SAPCD2 knockdown inhibited viability and cloning,hindered the G0/G1 phase of the cell cycle in UMUC3 and T24 cells,and decreased the migration and invasiveness of BC cells.SAPCD2 knockdown inhibited expression levels of cyclin D1,cyclin B1,N-cadherin,vimentin,Snail,β-catenin,c-Myc,and cyclin-dependent kinase 4,while the P21 and E-cadherin were raised by SAPCD2 knockdown.Furthermore,lithium chloride reversed the effects of SAPCD2 knockdown on the expression levels of the above proteins in UMUC3 and T24 cells.In vivo,SAPCD2 knockdown inhibited the volume,weight,and expression of Ki-67 andβ-catenin in tumors and increased the E-cadherin expression.Conclusion:SAPCD2 knockdown inhibits the malignant phenotype of BC via a pathway involvingβ-catenin.

New insights into ATR inhibition in muscle invasive bladder cancer:The role of apolipoprotein B mRNA editing catalytic subunit 3B

Background:Apolipoprotein B mRNA editing catalytic polypeptide(APOBEC),an endogenous mutator,induces DNA damage and activates the ataxia telangiectasia and Rad3-related(ATR)-checkpoint kinase 1(Chk1)pathway.Although cisplatin-based therapy is the mainstay for muscle-invasive bladder cancer(MIBC),it has a poor survival rate.Therefore,this study aimed to evaluate the efficacy of an ATR inhibitor combined with cisplatin in the treatment of APOBEC catalytic subunit 3B(APOBEC3B)expressing MIBC.Methods:Immunohistochemical staining was performed to analyze an association between APOBEC3B and ATR in patients with MIBC.The APOBEC3B expression in MIBC cell lines was assessed using real-time polymerase chain reaction and western blot analysis.Western blot analysis was performed to confirm differences in phosphorylated Chk1(pChk1)expression according to the APOBEC3B expression.Cell viability and apoptosis analyses were performed to examine the anti-tumor activity of ATR inhibitors combined with cisplatin.Results:There was a significant association between APOBEC3B and ATR expression in the tumor tissues obtained from patients with MIBC.Cells with higher APOBEC3B expression showed higher pChk1 expression than cells expressing low APOBEC3B levels.Combination treatment of ATR inhibitor and cisplatin inhibited cell growth in MIBC cells with a higher APOBEC3B expression.Compared to cisplatin single treatment,combination treatment induced more apoptotic cell death in the cells with higher APOBEC3B expression.Conclusion:Our study shows that APOBEC3B’s higher expression status can enhance the sensitivity of MIBC to cisplatin upon ATR inhibition.This result provides new insight into appropriate patient selection for the effective application of ATR inhibitors in MIBC.

Prognostic characterization of copper death-related immune checkpoint genes and analysis of immunologic and pharmacologic therapy in bladder cancer

Objective:Copper death-induced tumor cell death and immune checkpoint blockade therapy are highly selective.Combining their advantages and understanding their characteristics in bladder cancer is very important for the development of new targeted therapy.The identification of bladder cancer by screening the characteristic genes of copper death-related immune checkpoints provide a theoretical basis for the selection of adjuvant treatment options and the application of new targets.Methods:The expression samples of normal bladder tissue and bladder cancer were obtained from TCGA and GEO databases,and 13 cop-per death genes and 79 immune checkpoint genes were extracted from previous studies.The mRNA expression of prognostic genes was verified by qPCR.The copper death-related immune checkpoint genes were screened by correlation analysis to construct a prognostic model,and the differences in the efficacy of immunotherapy and chemotherapy between the high-risk group and the low-risk group were evaluated.Results:A prognostic model consisting of BTNL9,CD160,TNFRSF14 and TNFRSF18 was constructed.Its reliable predictive ability was proved in both databases,and qPCR showed that the expression levels of the four genes were significantly different between the normal group and the cancer cell group.The effect of immunotherapy in the lowrisk group was better than that in the high-risk group.Patients in the high-risk group had better chemotherapy efficacy.Conclusion:The copper death-related immune checkpoint gene model can accurately predict the prognosis of patients.Drug and immune analysis provide a basis for clinical treatment,and the discovery of potential targets provides a new solution for clinical decision-making.

Status quo and factors of depression and anxiety in patients with non-muscle invasive bladder cancer after plasma electrocision

BACKGROUND Bladder cancer is a type of cancer with a high incidence in men.Plasma electrosurgery(PES)is often used in the treatment of bladder cancer.Postoperative complications often cause depression and anxiety in patients after surgery.AIM To investigate the current state of depression and anxiety after PES in patients with non-muscle-invasive bladder cancer and analyze the factors affecting them.METHODS A retrospective study was conducted to compare the baseline data of patients by collecting their medical history and grouping them according to their mental status into negative and normal groups.Logistic regression analysis was used to explore the risk factors affecting the occurrence of anxiety and depression after surgery in patients with bladder cancer.RESULTS Comparative analyses of baseline differences showed that the patients in the negative and normal groups differed in terms of their first surgery,economic status,educational level,and marital status.A logistic regression analysis showed that it affected the occurrence of anxiety in patients with bladder cancer,and the results showed that whether the risk factors were whether or not it was the first surgery,monthly income between 3000 and 3000-6000,secondary or junior high school education level,single,divorced,and widowed statuses.CONCLUSION The risk factors affecting the onset of anxiety and depression in bladder cancer patients after PES are the number of surgeries,economic status,level of education,and marital status.This study provides a reference for the clinical treatment and prognosis of bladder cancer patients in the future.

Effects of OGFOD1 in bladder cancer progression and its prognostic significance:Insights from bioinformatics analysis

Background:Previous studies have established the role of 2-oxoglutarate and Fe(II)-dependent oxygenase domain–containing protein 1(OGFOD1)in oncogenesis.The objective of this investigation was to discern the diagnostic and prognostic relevance of OGFOD1 within the context of bladder cancer(BLCA)using bioinformatics methodologies.Methods:We collected RNA sequencing data from The Cancer Genome Atlas database and verified it using the GSE13507 dataset.Immunohistochemical analysis was based on data from the human protein atlas,and the protein-protein interaction network was constructed using the STRING database.Bioinformatics analysis was performed using the R application,analyzing the correlation between clinical characteristics and OGFOD1 expression,exploring the potential mechanisms of OGFOD1 in BLCA through Kyoto Encyclopedia of Genes and Genomes analysis,and evaluating the diagnostic and prognostic value of OGFOD1 expression in BLCA through receiver operating characteristic curve analysis,Kaplan-Meier analysis,and multivariate Cox analysis.Furthermore,a BLCA prognostic nomogram was constructed.Results:We report higher expression levels of OGFOD1 in BLCA specimens compared with those in noncancerous tissues;this can be used to predict the outcome of the disease.Further,results suggest that OGFOD1 is implicated in the activation of the peroxisome proliferator-activated receptor signaling cascade,potentially interacting with other genes linked to expression in promoting the onset and progression of BLCA.Conclusions:OGFOD1 is a promising candidate as a prognostic indicator in BLCA.

Landscape of urine biomarkers for bladder cancer:molecular function,cell-of-origin,and bibliometric trend

Background:The effective management of bladder cancer(BCa)depends on the early diagnosis and surveillance.Previous studies have explored numerous urinary molecules as potential biomarkers of BCa.However,the molecular functions and cell-of-origin profiles of these biomarkers are yet to be elucidated.In this study,we aimed to provide a comprehensive overview of the landscape of urinary biomarker genes for BCa.Methods:We conducted an exhaustive literature search in PubMed,through which 555 biomarker genes were identified.We then analyzed the BCa single-cell atlas to infer the cellular origin of these BCa urine biomarker genes and performed functional enrichment analysis to gain insights into the functional molecular implications of these biomarkers.Results:These genes are involved in tumor proliferation,angiogenesis,cellmigration,and cell death and are predominantly expressed in epithelial and stromal cells.Interestingly,our analysis ofmultiomics tumor data revealed a discordance between tissue and urine in terms of differential methylation and RNA expression,suggesting that biomarker discovery for liquid biopsies should ideally begin with the analysis of bodily fluids rather than relying interest and that test strategies incorporating multiple molecular markers represent an ongoing trend.Conclusions:Collectively,our study has built a landscape of BCa urine biomarker genes,uncovered molecular insights into these biomarkers,and revealed the bibliometric trends in this field,which will contribute to the discovery of novel biomarkers in the future.

Sex bias in FGFR3 somatic mutations in bladder cancer

Background:Strong sex disparities have been observed among patients with bladder cancer(BCa).FGFR3 is one of the most frequently mutated genes in bladder cancer,and there are inconsistencies in its frequency in male and female patients.Methods:Here,we conducted a meta-analysis comparing the FGFR3 somatic mutation frequency in men and women among 7351 patients with BCa from 18 cohorts.Results:We showed that female patients had a 1.32 times higher risk of having FGFR3 somatic mutations than males.This difference was attributed to mutations occurring at the 2 most frequently mutated sites,S249 and Y375.Additionally,nonsense mutations were more likely to be found in women,whereas indel/frameshift mutations were almost exclusively found in men;however,no difference was noted for missense mutations.Conclusions:A female sex bias in FGFR3 somatic mutationswas observed in BCa.Well-powered individual participant data analyses addressing the possible confounding effects of other factors(eg,age,ethnicity,smoking status,muscle invasiveness,and molecular subtype),as well as analyses integrating omics and functional investigations,are warranted to further validate and explain the mechanisms of the current findings.

Understanding the role of transmembrane 9 superfamily member 1 in bladder cancer pathogenesis

In this editorial we comment on the article by Wei et al,published in the recent issue of the World Journal of Clinical Oncology.The authors investigated the role of Transmembrane 9 superfamily member 1(TM9SF1)protein in bladder cancer(BC)carcinogenesis.Lentiviral vectors were used to achieve silencing or overexpression of TM9SF1 gene in three BC cell lines.These cell lines were then subject to cell counting kit 8,wound-healing assay,transwell assay,and flow cytometry.Proliferation,migration,and invasion of BC cells were increased in cell lines subjected to TM9SF1 overexpression.TM9SF1 silencing inhibited proliferation,migration and invasion of BC cells.The authors conclude that TM9SF1 may be an oncogene in bladder cancer pathogenesis.

TM9SF1 is implicated in promoting the proliferation and invasion of bladder cancer cells

Zhuo et al looked into the part of transmembrane 9 superfamily member 1(TM9SF1)in bladder cancer(BC),and evaluated if it can be used as a therapeutic target.They created a permanent BC cell line and tested the effects of TM9SF1 overexpression and suppression on BC cell growth,movement,invasion,and cell cycle advancement.Their results show that TM9SF1 can boost the growth,movement,and invasion of BC cells and their access into the G2/M stage of the cell cycle.This research gives a novel direction and concept for targeted therapy of BC.

Chemosensitizing Effect of Monk Fruit Extract on Human Bladder Cancer Cells

The outcomes of chemotherapy have been unsatisfactory with the palpable side effects. We hypothesized that natural products might help improve chemotherapy with few side effects. Recently, we came across the bioactive extracts of monk fruit (Siraitia grosvenori) with anticancer activity. We then investigated if these extracts might have chemosensitizing effect to improve the efficacy of drugs clinically used today. Four different drugs, cisplatin (CPL), carboplatin (CBL), mitomycin C (MMC), and gemcitabine (GEM), were used in this study. Human bladder cancer T24 cells were treated with each drug itself or drug combined with either LLE or MOG (two types of monk fruit extracts). Cell viability was determined to assess anticancer effect and also explored the anticancer mechanism of such combinations, focusing on the status of glycolysis, cell cycle, and chromatin structure. Cell viability test showed that all drugs had anticancer activity, reducing cell viability, but only CPL showed the enhanced anticancer effect when combined with LLE (not with MOG). The rest of three drugs had no such effects with LLE or MOG. The CPL/LLE combination was found to disrupt glycolysis, by inhibiting hexokinase activity, resulted in the decreased ATP synthesis. This combination also blocked the cell cycle progression, due to a G1 cell cycle arrest. Moreover, the two epigenetic regulators, DNA methyltransferase and histone deacetylase, were inactivated with the combination, indicating chromatin modifications. Ultimately, these treated cells were found to undergo apoptosis. In conclusion, anticancer activity of CPL can be significantly enhanced with LLE. This chemosensitizing effect is attributed to the glycolysis inhibition, a G1 cell cycle arrest, and chromatin modifications, ultimately leading to apoptosis. Thus, certain natural products such as LLE could be used as an adjuvant agent in current chemotherapy, improving the drug efficacy but minimizing side effects.

A Prognostic Biomarker for Bladder Cancer Correlated with Immune Infiltration Is PAEP

Background: A major cause of cancer death worldwide is bladder cancer, which is the most common malignant tumor of the urinary tract. PAEP is a member of the kernel lipocalin superfamily whose members share relatively low sequence similarity but have highly conserved exon/intron structure and three-dimensional protein folding. Most lipocalins are clustered on the long arm of chromosome 9. The purpose of this study was to clarify the correlation between PAEP expression level and bladder cancer. Methods: In the TCGA database, we obtained clinical and RNA sequencing data of 431 BLCA patients, including 412 BLCA tissues and 19 normal bladder tissues in the study. Analyses of bioinformatics were conducted in this study to determine the role of PAEP in bladder cancer. A quantitative real-time PCR method was used to quantitate the gene expression profile. Additionally, the effect of PAEP on tumor immune infiltration and prognosis was analyzed. Results: PAEP was a poor prognostic biomarker of bladder cancer because it was significantly upregulated. bladder cancer patients with higher PAEP expression had poor outcomes. An AUC of 0.780 was calculated from the area under the ROC curve. PAEP was associated with T stage, pathologic stage, Histologic grade and Subtype of bladder cancer patients, and served as an independent predictor of overall survival in bladder cancer patients. Functional enrichment analysis revealed PAEP was obviously enriched in pathways connected with carcinogenesis and immunosuppression. The expression of PAEP was significantly associated with tumor immune cells and immune checkpoints according to ssGSEA and Spearman correlation analysis. Conclusions: In this study, we screened and detected a mRNA, PAEP is a prognostic and immune-related biomarker in BLCA, which may contribute to the early diagnosis and treatment of BLCA.