Transitional Cell Carcinoma Patients Research Articles

Crosstalk between autophagy and bladder transitional cell carcinoma by autophagy-related lncRNAs.

The aim of this study was to investigate the crosstalk between autophagy and bladder transitional cell carcinoma (TCC) by autophagy-related long noncoding RNAs (lncRNAs). A total of 400 TCC patients from The Cancer Genome Atlas were enrolled in this study. We identified the autophagy-related lncRNA expression profile of the TCC patients and then constructed a prognostic signature using the least absolute shrinkage and selection operation and Cox regression. Risk, survival, and independent prognostic analyses were carried out. Receiver operating characteristic curve, nomogram, and calibration curves were explored. Gene Set Enrichment Analysis was employed to verify the enhanced autophagy-related functions. Finally, we compared the signature with several other lncRNA-based signatures. A 9-autophagy-related lncRNA signature was established by least absolute shrinkage and selection operation-Cox regression that was significantly associated with overall survival in TCC. Among them, 8 of the 9 lncRNAs were protective factors while the remaining was a risk factor. The risk scores calculated by the signature showed significant prognostic value in survival analysis between the high- or low-risk groups. The 5-year survival rate for the high-risk group was 26.0% while the rate for the low-risk group was 56.0% (P < .05). Risk score was the only significant risk factor in the multivariate Cox regression survival analysis (P < .001). A nomogram connecting this signature with clinicopathologic characteristics was assembled. To assess the performance of the nomogram, a C-index (0.71) was calculated, which showed great convergence with an ideal model. The Gene Set Enrichment Analysis results demonstrated 2 major autophagy-related pathways were significantly enhanced in TCC. And this signature performed a similar predictive effect as other publications. The crosstalk between autophagy and TCC is significant, and this 9 autophagy-related lncRNA signature is a great predictor of TCC.

Abstract 5546: Urine metabolomic biomarkers discovery for bladder cancer diagnostics

Abstract Current estimates in the United States for 2022 are about 81,180 new cases of bladder cancer diagnosis with about 17,100 deaths from the disease (American Cancer Society). Urothelial carcinoma, also known as transitional cell carcinoma (TCC), is the most common type of bladder cancer, approximately 70% of newly diagnosed TCC patients have non-muscle invasive bladder cancer (NMIBC) tumors. The gold standards for initial diagnosis and recurrence of TCC, cystoscopy and cytology, are both limited by their inability to visualize certain areas within the bladder or detect low grade tumors. Moreover, these tests are associated with false positive profiles, with potential for abnormal readouts even in individuals with no obvious signs of cancer. High recurrence rate predicates the need for constant monitoring of signs and symptoms associated with bladder disease following initial diagnosis, and non-invasive diagnostic modalities to detect both recurrent and primary early-stage tumors are a critical unmet need. In this study, comprehensive metabolomic profiling from human urine samples was used to identify and validate a panel of metabolites as potential biomarkers of bladder cancer. Urine samples from 439 total subjects (comprised of 66 bladder cancer, 119 history of bladder cancer but no bladder cancer at time of urine sampling, 58 hematuria subjects, 48 renal cell carcinoma, 58 prostate cancer, and 89 healthy subjects) were analyzed using a proprietary global untargeted metabolomic platform. A follow-up study to determine the reproducibility of the initial data set was conducted with 162 urine samples from subjects with bladder cancer that were either recurrent or primary, or with a negative diagnosis for bladder cancer with a previous history of bladder cancer or had hematuria or urinary voiding issues. Utilizing both data sets, eight biochemicals (lactate, gluconate, palmitoyl sphingomyelin, acetylcarnitine, choline phosphate, succinate, and adenosine) were identified as potential urine biomarkers for bladder cancer. In addition, 3-hydroxybutyrate (BHBA), 2-hydroxybutyrate (AHB), and adipate were identified as potential urine biomarkers for urological cancers. In total, 37 biochemicals have now been identified with having the potential to serve as urine bladder cancer biomarkers, and the majority of the biochemicals identified as biomarkers were associated with biochemical pathways previously shown to be perturbed in bladder tumors. The performance characteristics of the identified biochemicals in the detection of bladder cancer will be reported. Citation Format: Andrew J. Schwab, Matthew W. Mitchell, Edward D. Karoly, Rangaprasad Sarangarajan. Urine metabolomic biomarkers discovery for bladder cancer diagnostics. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5546.

Assessment of Outcomes of Maintenance Gemcitabine after Standard Chemotherapy in Metastatic Bladder Transitional Cell Carcinoma Patients

Assessment of Outcomes of Maintenance Gemcitabine after Standard Chemotherapy in Metastatic Bladder Transitional Cell Carcinoma Patients

Overall and Cancer-Specific Survival in Patients With Renal Pelvic Transitional Cell Carcinoma: A Population-Based Study.

Background: Renal pelvic transitional cell carcinoma (TCC) is a relatively rare tumor. This study aimed to develop two prognostic nomograms to predict overall survival (OS) and cancer-specific survival (CSS) in renal pelvic TCC patients.Methods: Clinicopathological and follow-up data of renal pelvic TCC patients diagnosed between 2010 and 2015 were retrieved from the Surveillance, Epidemiology, and End Result (SEER) database. Univariate and multivariate Cox regression analyses were used to screen the independently prognostic factors. These independently prognostic factors were then utilized to build nomograms for predicting 3-, 4-, and 5- years OS and CSS of patients with renal pelvic TCC. The nomograms were assessed by calibration curve, receiver operating characteristic (ROC) curve and decision curve analysis (DCA).Results: A total of 1,979 renal pelvic TCC patients were enrolled. Age, tumor size, histological type, American Joint Committee on Cancer (AJCC) stage, surgery, chemotherapy, bone metastasis and liver metastasis were confirmed as independently prognostic factors for both OS and CSS. The areas under the ROC curves (AUCs) of OS nomogram at 3-, 4- and 5-years in the training cohort were 0.797, 0.781, and 0.772, respectively, and the corresponding AUCs in the validation cohort were 0.813, 0.797, and 0.759, respectively. The corresponding AUCs of CSS nomogram were all higher than 0.800. The calibration curves and DCA indicated that both nomograms had favorable performance. Subgroup analyses showed that both nomograms perform in well and poorly differentiated patients.Conclusion: In conclusion, we successfully developed and validated two valuable nomograms to predict the OS and CSS for renal pelvic TCC patients. The nomograms incorporating various clinicopathological indicators can provide accurate prognostic assessment for patients and help clinicians to select appropriate treatment strategies.

Extraperitoneal Laparoscopic Radical Cystectomy With Preservation of Fertility for the Treatment of Ewing Sarcoma: The First Report of a Reliable Surgical Method

To improve the complications of traditional laparoscopic radical cystectomy (LRC), a novel technique of extraperitoneal laparoscopic radical cystectomy (ELRC) with preservation of fertility was described. Selected patients with bladder cancer were treated with the ELRC technique. The seminal vesicles and the vas deferens were preserved. Patient's perioperative conditions, tumor prognosis, and follow-up data were analyzed retrospectively. We successfully completed ELRC surgery in dozens of patients. The orthotopic ileal neobladder was placed in the extraperitoneal area, completely preserving the peritoneum. The postoperative complications caused by postoperative peritoneal loss were reduced. Moreover, the perioperative period was strictly managed with the concept of enhanced recovery after surgery (ERAS). We described the operation process in detail through a typical case of a child. All patients were free of complication at short-term follow-up, and reported satisfied sexual function with normal erections. The ELRC technique has benefits in terms of decreased ileus, reoperation rates, hospital stay, ease of management of urinary leaks, and improves the patient quality of life. ELRC is also an oncologically safe approach with excellent significant functional outcomes in carefully selected transitional cell carcinoma (TCC) or non-TCC patients who expect to maintain sexual function and fertility, especially for young patients. In addition, more patient groups and longer follow-ups are needed to further understand the safety and practicality of the ELRC technology.

Application of SPRi Biosensors for Determination of 20S Proteasome and UCH-L1 Levels in the Serum and Urine of Transitional Bladder Cancer Patients

The ubiquitin–proteasome system (UPS) participates in the degradation of proteins which play an important role in regulating the cell cycle, apoptosis, and angiogenesis, as well as in the immune system. These processes are important in carcinogenesis. Transitional cell carcinoma (TCC) is one of the predominant types of bladder cancer. The relationship between the ubiquitin–proteasome system and cancer progression has become a topic of increasing interest among researchers. In this work, we propose an application of surface plasmon resonance imaging (SPRi)-based biosensors for the detection of 20S proteasome and ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) in the blood serum and urine of patients with TCC. The aim of the study was to determine 20S proteasome and UCH-L1 concentrations and to correlate the results with clinicopathological parameters. The group of subjects consisted of 82 patients with confirmed TCC, in addition to a control group of 27 healthy volunteers. It was found that 20S proteasome and UCH-L1 concentrations were significantly elevated in both the serum and urine of TCC patients, compared with the healthy subjects. There was a correlation between 20S proteasome concentrations in serum and urine, as well as between serum proteasome and UCH-L1 concentration. The SPRi biosensor sensitive to 20S proteasome using PSI inhibitor as the receptor, and the SPRi biosensor sensitive to the UCH-L1 protein using the protein-specific antibody as the receptor is suitable for the determination of 20S proteasome and UCH-L1 in body fluids and can serve as useful tools in the investigation of cancer biomarkers.

Establishment of Canine Transitional Cell Carcinoma Cell Lines Harboring BRAF V595E Mutation as a Therapeutic Target.

Transitional cell carcinoma (TCC) is the most common malignant tumor of the canine urinary tract and tends to have a poor prognosis due to its invasive potential. Recent studies have reported that up to 80% of canine urothelial carcinoma has the BRAF V595E mutation, which is homologous to the human V600E mutation. Activating the BRAF mutation is an actionable target for developing effective therapeutic agents inhibiting the BRAF/mitogen-activated protein kinase (MAPK) pathway in canine cancer as well as human cancer. We established novel canine TCC cell lines from two tumor tissues and one metastatic lymph node of canine TCC patients harboring the BRAF V595E mutation. Tumor tissues highly expressed the BRAF mutant and phosphorylated extracellular signal-related kinases (ERK)1/2 proteins. The derived cell lines demonstrated activated MAPK pathways. We also evaluated the cell lines for sensitivity to BRAF inhibitors. Sorafenib, a multiple kinase inhibitor targeting RAF/vascular endothelial growth factor receptor (VEGFR), successfully inhibited the BRAF/MAPK pathway and induced apoptosis. The established canine TCC cell lines responded with greater sensitivity to sorafenib than to vemurafenib, which is known as a specific BRAF inhibitor in human cancer. Our results demonstrated that canine TCC cells showed different responses compared to human cancer with the BRAF V600E mutation. These cell lines would be valuable research materials to develop therapeutic strategies for canine TCC patients.

Unusual co-occurrence of cold agglutinin disease in a bladder transitional cell carcinoma patient with unexplained anemia and cold-related symptoms.

Unusual co-occurrence of cold agglutinin disease in a bladder transitional cell carcinoma patient with unexplained anemia and cold-related symptoms.

Increased expression of POLR3G predicts poor prognosis in transitional cell carcinoma.

BackgroundPrevious studies have shown that RNA Polymerase III Subunit G (POLR3G) has oncogenic effects in cultured cells and mice. However, the role of POLR3G in transitional cell carcinoma (TCC) has not been reported. This study explores the potential of POLR3G as a novel molecular marker for TCC.MethodsThe RNA sequencing data and clinical information of patients with TCC were downloaded from The Cancer Genome Atlas official website. Transcriptome analysis was performed as implemented in the edgeR package to explore whether POLR3G was up-regulated in TCC tissues compared to normal bladder tissues. The expression of POLR3G in bladder cancer cell line T24 and human uroepithelial cell line SV-HUC-1 were detected via quantitative real time polymerase chain reaction (qRT-PCR). Correlations between POLR3G expression and clinicopathological characteristics were analyzed using Mann-Whitney U test or Kruskal-Wallis H test. Clinicopathological characteristics associated with overall survival were explored using the Kaplan-Meier method and Cox regression analyses. Gene set enrichment analysis (GSEA) was performed to explore the associated gene sets enriched in different POLR3G expression phenotypes and the online tool Tumor IMmune Estimation Resource (TIMER) was used to explore the correlation between POLR3G expression and tumor immune infiltration in TCC.ResultsTranscriptome analysis showed that POLR3G was significantly up-regulated in TCC tissues compared to normal bladder tissues. Furthermore, qRT-PCR revealed high expression of POLR3G in T24 cells compared to SV-HUC-1 cells. Overall, POLR3G expression was associated with race, tumor status, tumor subtype, T classification, and pathological stage. Kaplan-Meier survival analysis revealed that higher POLR3G expression was associated with lower overall survival. The univariate Cox regression model revealed that age at diagnosis, pathological stage, and POLR3G expression were associated with prognosis of TCC patients. Further multivariate analyses identified these three clinicopathological characteristics as independent prognostic factors for overall survival. GSEA analysis showed that several gene sets associated with tumor development and metastasis, including TGF-β signaling, PI3K-AKT-mTOR signaling, and IL6-JAK-STAT3 signaling, were significantly enriched in POLR3G high expression phenotype. Immune infiltration analysis revealed that the expression of POLR3G was significantly correlated with infiltrating levels of immune cells, including CD8+ T cells, neutrophils, and dendritic cells; and the expression of POLR3G was also significantly correlated with the expression of immune checkpoint molecules, such as PD1, PD-L1, PD-L2, CTLA4, LAG3, HAVCR2, and TIGIT.ConclusionsPOLR3G was up-regulated in TCC and high POLR3G expression correlated with poor prognosis. POLR3G can potentially be used as a prognostic marker for TCC and might be of great value in predicting the response to immunotherapy.

Antitumor activity of an oncolytic measles virus against canine urinary bladder transitional cell carcinoma cells

The prognosis of canine transitional cell carcinoma (TCC) of urinary bladder is generally poor because it is difficult to diagnose at early stages and conventional therapies, such as surgical resection and/or chemotherapy, are often not curative treatments. Based on our previous report that recombinant measles virus (rMV-SLAMblind) therapy could be a new treatment for canine mammary tumor, the applicability of rMV-SLAMblind in canine urinary bladder TCC was examined in this study. A canine TCC cell line was established from a TCC patient dog by transplanting a piece of the tumor mass into an immunodeficient mouse and then isolating the primary TCC cells from the grown tumor mass. The primary cultured cells, named TCC-NU1, express nectin-4, a receptor for rMV-SLAMblind infection. The rMV-SLAMblind infected TCC-NU1 cells, and dose-dependently showed cell cytotoxicity. Moreover, intratumoral administration of rMV-SLAMblind in a xenograft model bearing TCC-NU1 cells significantly suppressed the tumor growth reducing the endpoint mass of tumors in treated mice compared to control mice. These results suggest that virotherapy with rMV-SLAMblind be a new candidate therapy for canine TCC.

A functional variant rs1464938 in the promoter of fibroblast growth factor 12 is associated with an increased risk of bladder transitional cell carcinoma

Increasing evidence shows that inflammation plays critical roles in the tumorigenesis of bladder cancer. Fibroblast growth factor 12 (FGF12), a kind of inflammatory cytokine, is located in the region of 3q28 that has been demonstrated to be a bladder cancer risk locus by genome wide association study (GWAS). In this study, we aimed to investigate the association of GWAS signal rs710521 and rs884309 and rs1464938 in the promoter of FGF12 with the risk of bladder transitional cell carcinoma (TCC). The polymorphisms were analyzed by using a Taqman assay in 331 TCC patients and 516 age-, gender-, and ethnicity-matched controls. The expression levels of FGF12 mRNA were examined in TCC and non-cancerous normal tissues by using quantitative real-time PCR and the luciferase activity was determined by using the Dual-Luciferase Assay System. The rs1464938 AA genotype and A allele were associated with a significantly increased risk of TCC (AA vs. GG: adjusted OR = 2.54, 95% CI, 1.49–4.35, P < 0.001; AA vs. AG/GG: adjusted OR = 2.25, 95% CI, 1.36–3.71, P = 0.002; A vs. G: adjusted OR = 1.44, 95% CI, 1.15–1.80, P = 0.001, respectively). Haplotype analysis showed that rs884309G- rs1464938A haplotype was associated with an increased risk of TCC (OR = 1.61, 95% CI, 1.23–2.11, P = 0.001). Functional analysis showed that the rs1464938 AG/AA genotypes exhibited higher levels of FGF12 mRNA in TCC tissues and the rs1464938 A allele enhanced FGF12 promoter activity (P < 0.05). These findings suggest that the rs1464938 A allele at the 3q28 locus contribute to the development of TCC by regulating FGF12 expression levels.

N-acetyltransferase 2 polymorphism is associated with bladder cancer risk: An updated meta-analysis based on 54 case-control studies.

N-acetyltransferase 2 (NAT2) polymorphism could participate in the metabolism of carcinogens through regulating the activity of a series of critical enzymes. However, the effects of NAT2 polymorphism on bladder cancer (BCa) risk were still inconclusive. In order to illustrate whether NAT2 polymorphism may influence the susceptibility to BCa, we conducted this updated meta-analysis. Databases including PubMed, Medline, Embase, Web of Science, Cochrane Library, and China National Knowledge Infrastructure(CNKI) were systematically retrieved and we applied MetaGenyo to perform final meta-analysis. Odds ratios (ORs) as well as 95% confidence intervals (CIs) were calculated and Bonferroni method was applied to correct the P-value for multiple comparisons. The registration of this study protocol is at PROSPERO and ID is CRD42019133957. Ultimately, 54 case-control studies were identified for final meta-analysis (13343 BCa cases and 18,586 controls). Overall analysis indicated that the slow genotype in NAT2 polymorphism was obviously associated with BCa risk (PBonferroni<0.001). Subgroup analyses demonstrated that significant risk with the slow genotype was observed in Caucasians, Asians, smokers, non-exposed individuals, high grade bladder cancer (HGBC) patients and muscle-invasive bladder cancer (MIBC) patients. In addition, the intermediate NAT2 genotype was revealed to increase the BCa risk of Asians and transitional cell carcinoma (TCC) patients. However, no correlation was identified in Africans with the NAT2 polymorphism. The slow NAT2 genotype was identified to be the risk genotype for BCa. The intermediate genotype could serve as the candidate risk genotype. The gene-smoking interaction with NAT2 polymorphism might accelerate the tumor progression.

Copper and zinc levels in plasma and cancerous tissues and their relation with expression of VEGF and HIF-1 in the pathogenesis of muscle invasive urothelial bladder cancer: a case-controlled clinical study.

To evaluate Cu and Zn levels in bladder cancer (BC) patients and their relationship with expression of vascular endothelial growth factor (VEGF) and hypoxia-inducible factor 1 (HIF-1). Plasma levels of Cu and Zn were determined in 66 transitional bladder cell carcinoma patients (BC group) and 60 matched controls. The concentration of Cu and Zn as well as the expressions of both VEGF and HIF-1 were also estimated in cancerous and non-cancerous bladder tissues in the BC group. The results showed that plasma Cu and Cu/Zn ratio were significantly higher in BC group when compared with the control group. In contrast, the plasma Zn in BC group was significantly lower than in the controls. Comparing levels of Cu and Zn in cancerous and non-cancerous bladder tissues among the BC group indicated a significantly higher Cu levels in the cancerous tissues, while Zn levels was significantly lower. There were higher expressions of both VEGF and HIF-1 in the cancerous samples. Moreover, the Cu concentration in cancerous tissues was significantly correlated with expressions of VEGF and HIF-1. Logistic regression analysis revealed that the increase in plasma Cu/Zn ratio and plasma Cu and the decrease in plasma Zn may be risk factors for development of bladder cancer. We concluded that alteration of plasma and bladder tissue levels of both Cu and Zn is correlated with pathogenesis of bladder cancer. The increase in Cu level in cancerous tissues of BC group has an important role in angiogenesis in bladder cancer cells.

The impact of marital status on the survival of transitional cell carcinoma of the bladder.

578 Background: Marital status is one of the multiple lifestyle factors that affect the survival of several malignancies. Prior literature has demonstrated that married individuals have better survival in cases of transitional cell carcinoma (TCC). In this study, we aim to demonstrate the association in a large cohort of patients. Methods: Data of TCC patients with known marital status who were diagnosed between 1973 and 2015 in the US was obtained using the Surveillance Epidemiology and End Results (SEER) database. We compared the overall and cancer-specific survival of patients according to their marital status using Kaplan-Meier test and multivariable covariate-adjusted Cox models. Results: We reviewed 204,862 TCC patients, of which 64.26%, 10.64%, 1.01%, 7.31%, and 16.78% were married, single, separated, divorced, and widowed, respectively. Married patients had the highest overall survival (median 123 months), followed by single patients (median 111 months), divorced (median 102 months), separated (median 60 months), and widowed (median 43 months). Bladder cancer-specific survival followed relatively similar trends with married patients having significantly better survival when compared to other groups. When we adjusted for age, sex, race, stage, grade, and undergoing cancer-targeted surgery, married patients had better survival outcomes when compared to single patients (HR = 1.322, p-value &lt; 0.001), separated patients (HR = 1.409, p-value &lt; 0.001), divorced patients (HR = 1.358, p-value &lt; 0.001), and widowed patients (HR = 1.242, p-value &lt; 0.001). Conclusions: Our results demonstrate a clear survival advantage in cases of transitional cell carcinoma of the bladder with married individuals having the highest overall and cancer-specific median survival. These results shed the light on the lifestyle and the psychosocial factors, including the social support that married patients may have comparing to unmarried patients, and their effect on the disease prognosis and survival. Understanding the social and psychological factors associated with the observed disparity may help enhance management plans for affected patients.

The expression of apolipoproteina1 and its correlation with infiltration of urologic neoplasm.

BackgroundTo explore the differential expression of apolipoproteinA1 (APOA1) in urologic neoplasm patient compared with controls, as well as investigates whether APOA1 correlated with infiltration of urologic neoplasm.MethodsA total of 59 tissue sections of surgically-resected urologic neoplasm and 6 cases of normal tissue sections were collected. Fourteen cases of urine samples from transitional cell carcinoma patients and 6 cases urine samples from controls were also applied in this experiment. We also selected 6 cases of fresh bladder transitional cell carcinoma tissues. The urologic neoplasm tissue sections were classified into infiltration and non-infiltration urologic neoplasm groups. The expressions of APOA1 between urologic neoplasm and normal control were detected by Western blot, Immunohistochemistry and qRT-PCR. The method of Immunohistochemistry was applied to examine the differences of APOA1 expression between infiltration and non-infiltration urologic neoplasm tissue section groups.ResultsCompared with none expression in normal controls, APOA1 was exhibited higher level in urologic neoplasm patient’s urine and fresh bladder transitional cell carcinoma tissues (P<0.05). There were statistical differences of APOA1 between infiltration and non-infiltration urologic neoplasm tissue section groups. APOA1 expressions were found to be up-regulated in the infiltration neoplasm tissue sections compared to non-infiltration group (P<0.001).ConclusionsAPOA1 could act as a valuable biomarker for predicting the occurrence and development of urologic neoplasm.

Bullous lichen planus-like reactions in a patient with renal cancer after receiving anti-programmed cell death-1 therapy

Anti-programmed cell death 1 (anti-PD-1) agent is a promise in cancer immunotherapy for various advanced malignancies, but dermatologic toxicities are common during therapy. We report one advanced transitional cell carcinoma patient who developed multiple bullous skin lesions over bilateral lower extremities after anti-PD-1 antibody pembrolizumab treatment. Skin biopsy revealed subepidermal cleft, wedge-shaped hypergranulosis, saw-tooth acanthosis, and presence of interface band-like lymphohistiocytic infiltrate compatible with bullous lichen planus-like reactions. Potent topical steroid and temporary cessation of pembrolizumab relieved the skin eruptions. Early recognition and appropriate management of rare bullous dermatologic toxicities are critical in patients receiving immune checkpoint blockade therapy.

Investigating the Levels of Shed Extracellular Domain of HER2 Protein in the Sera of Bladder Cancer Patients

Background: Receptor tyrosine-protein kinase ERBB2, also known as human epidermal growth factor receptor-2 (HER2), is heterogeneously expressed in a variety of human cancers, including bladder cancer. Based on previous studies that show its association with bladder cancer progression, HER2 has been included in novel multiplatform biomarkers for prediction of bladder cancer prognosis. However, the clinical significance of HER2 status remains underinvestigated and poorly linked to the patients’ clinicopathological features. Here, we aim to scrutinize the levels of the extracellular domain of HER2 in the sera of bladder cancer patients and correlate these levels with clinicopathological features of the tumor.Methods: In the present analytical cross-sectional study, we enrolled 60 pathologically confirmed bladder cancer patients along with 20 age-sex matched healthy controls, and compared their serum HER2 levels as measured by enzyme-linked immunosorbent assay.Results:We observed no statistically significant difference when comparing the levels of HER2 in the sera of cases and controls (P>0.05). Interestingly, serum HER2 levels of controls were higher than bladder cancer patients who had lymph node metastasis (P=0.036). Serum levels of HER2 were also higher in controls than bladder cancer patients with perineural invasion (P=0.028). We observed significantly higher HER2 serum levels in transitional cell carcinoma patients in comparison to non-transitional cell carcinoma patients (P=0.016).Conclusion: Our observations are suggestive of the absence of any association between bladder cancer prognostic factors and serum HER2 levels. To draw any definitive conclusion, further studies with larger sample sizes that examine the presence of neutralizing auto-antibodies against serum HER2, immunohistochemistry examination of HER2 in bladder tumor and lymph node samples, and urinary HER2 levels, along with measurement of its serum levels would be helpful.

Urinary exosomal expression of long non-coding RNAs as diagnostic marker in bladder cancer.

BackgroundLong non-coding RNAs (lncRNAs) and exosomes have been regarded as components of cell signal transmission that modulate indigenous cellular microenvironments. Exosomes also participate in relocation of functional lncRNAs between cells.MethodsIn the present study, we evaluated expression of LINC00355, LINC00958, UCA1-201, UCA1-203, and MALAT1 lncRNAs in urinary exosomes isolated from transitional cell carcinoma (TCC) of bladder, non-malignant urinary disorders, and normal subjects.ResultsLINC00355, UCA1-203, and MALAT1 expression was significantly higher in TCC patients compared to controls (non-malignant or normal samples). However, UCA1-201 expression was significantly decreased in TCC patients compared with controls. LINC00355 and MALAT1 expression was significantly lower in cigarette smokers and opium-addicted TCC patients, respectively. On the other hand, LINC00355 expression tended to be higher in opium-addicted TCC patients. The proposed panel of lncRNAs (composed of UCA1-201, UCA1-203, MALAT1, and LINC00355) had 92% sensitivity and 91.7% specificity for diagnosis of bladder cancer from normal samples.ConclusionTranscript levels of lncRNAs in urinary exosomes are potential diagnostic bio-markers in bladder cancer.

46 - Urinary bladder transitional cell carcinoma in patients of age below 40

46 - Urinary bladder transitional cell carcinoma in patients of age below 40

Hsa-microRNA-101-3p expression in human urinary bladder cancer: Correlation with tumor pathology

IntroductionMicroRNAs (miRs) are a class of small, conserved, non-protein-coding RNAs that regulate gene expression by controlling translation of target messenger RNA. In cancer, miRs can act either as tumor suppressors or oncogenes. Reduced expression of hsa-miR-101-3p has been observed in different types of cancers, and was thus considered to be a tumor suppressor. In urinary bladder cancer (BC) cell lines, hsa-miR-101-3p was found to suppress cancer cells motility, however studies in human BC patients, correlating hsa-miR-101-3p expression to pathological findings are very limited. This study aims at assessing hsa-miR-101-3p expression in human BC in correlation to tumor pathology in transurethral resection biopsies. Material and methodsTransuretheral bladder tissue specimens were collected from 100 bladder cancer patients. Only bladder transitional cell carcinoma (BTCC) patients (n = 80) were considered. Total RNA was extracted and following reverse transcription, expression of hsa-miR-101-3p was assessed by quantitative real time PCR using Taqman assay. The fold change for hsa-miR-101-3p expression between malignant and surrounding non-malignant tissues was calculated using relative quantification method. Expression of hsa-miR-101-3p was correlated to tumor stage, grade, and lymphatic/ vascular involvement. ROC curve was done to calculate the discriminative ability of hsa-miR-101-3p expression between malignant and non-malignant tissues. ResultsHsa-miR-101-3p was significantly under-expressed in all malignant versus non-malignant tissue samples (median 13.6 (9.8–19.4) vs. median 10.9 (7.4–16.2), p < 0.001) respectively. Mann-Whitney test showed statistically significant hsa-miR-101-3p underexpression in high vs. low tumor grades (p < 0.001), and T2 vs. T1 tumor stages (p < 0.001). There was no significant association between hsa-miR-101-3p underexpression and lymphatic/vascular invasion. ROC curve demonstrated hsa-miR-101-3p to highly discriminate between malignant and non-malignant tissue (p < 0.001).At cut-off value >10.85, hsa-miR-101-3p showed sensitivity of 83% and specificity of 56%. ConclusionsHsa-miR-101-3p can highly discriminate between malignant and non-malignant samples in BTCC, and seems to associate with tumor progression and aggressiveness. It might be a promising diagnostic and perhaps prognostic marker for BTCC.