Gender Differences in Urothelial Bladder Cancer: Effects of Natural Killer Lymphocyte Immunity

Livas, Lydia; Presnell, Steven R.; Sexton, Morgan; Wang, Peng

doi:10.3390/jcm10215163

Cited by 6 publications

(4 citation statements)

References 245 publications

(400 reference statements)

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“…It is known that BC is a disease of the elderly (30). Macroscopic haematuria, male sex, and age over 60 years have been identified as independent risk factors for BC (31,32). The ratio of male to female for BC was 3:1 consistent with other reports.…”

Section: Discussionsupporting

confidence: 87%

Biomarkers to assess the risk of bladder cancer in patients presenting with haematuria are gender-specific

Duggan

O’Rourke²,

Anderson³

et al. 2022

Front. Oncol.

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IntroductionHaematuria is a common red flag symptom of urinary tract cancer. Bladder cancer (BC) is the most common cancer to present with haematuria. Women presenting with haematuria are often underdiagnosed. Currently, no gender-specific tests are utilized in clinical practice. Considerable healthcare resources are needed to investigate causes of haematuria and this study was set up to help identify markers of BC. The aim of the study was to define biomarker algorithms in haematuria patients using an expanded panel of biomarkers to diagnose BC and investigate if the algorithms are gender-specific.Materials and MethodsA total of n=675 patients with a history of haematuria were recruited from Northern Ireland hospitals. Patients were collected on a 2:1 ratio, non-BC (control) n=474: BC n=201. A detailed clinical history, urine and blood samples were collected. Biomarkers, known to be involved in the pathobiology underlying bladder carcinogenesis were investigated. Biomarkers differentially expressed between groups were investigated using Wilcoxon rank sum and linear regression.ResultsBiomarkers were gender specific. Two biomarker-algorithms were identified to triage haematuria patients; male – u_NSE, s_PAI-1/tPA, u_midkine, u_NGAL, u_MMP-9/TIMP-1 and s_prolactin (u=urine; s=serum); sensitivity 71.8%, specificity 72.8%; AUROC 0.795; and female urine biomarkers - IL-12p70, IL-13, midkine and clusterin; sensitivity 83.7%, specificity 79.7%; AUROC 0.865. Addition of the clinical variable infection to both algorithms increased both AUROC to 0.822 (DeLong p=0.014) and to 0.923 (DeLong p=0.004) for males and females, respectively. Combining clinical risk factors with biomarker algorithms would enable application of the algorithms to triage haematuria patients.ConclusionUsing gender-specific biomarker algorithms in combination with clinical risks that are associated with BC would allow clinicians to better manage haematuria patients and potentially reduce underdiagnosis in females. In this study, we demonstrate, for the first time, that blood and urine biomarkers are gender-specific when assessing risk of BC in patients who present with blood in their urine. Combining biomarker data with clinical factors could improve triage when referring patients for further investigations.

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Section: Discussionsupporting

confidence: 87%

Biomarkers to assess the risk of bladder cancer in patients presenting with haematuria are gender-specific

Duggan

O’Rourke²,

Anderson³

et al. 2022

Front. Oncol.

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“…32 Also, other factors such as those of a genetic and hormonal nature may make women more susceptible to the disease. 33 The Hepatitis C virus is considered one of the oncoviruses that are connected to the development of cancer. These extrahepatic cancers include lymphoma, 12 renal cell carcinoma (RCC), 14 TCC, and head and neck squamous cell carcinoma.…”

Section: Discussionmentioning

confidence: 99%

The Immunohistochemical Staining of Vimentin and E-Cadherin in Bladder Cancer Patients Infected with Hepatitis C Virus

Ismael¹,

Qaddoori²,

Sha'ban³

et al. 2023

J. Pure Appl. Microbiol.

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The invasion and spread of cancer cells are two of the most notable characteristics of malignant tumors. Recent studies suggest that the epithelial-mesenchymal transition (EMT) has been linked to this significant occurrence. It is linked to the absence of the epithelial brow and the presence of mesenchymal facial hair. The aims of the present study were to explore the immunohistochemical staining of vimentin and E-cadherin ex vivo as EMT markers and assess their potential as predictive biomarkers for transitional cell cancer (TCC). In this study, 55 paraffin-embedded biopsies from TCC patients and 10 autopsies that appeared to be normal were included. Immunohistochemistry was used to produce patterns of vimentin and E-cadherin expression. When compared to female patients, the expression of E-cadherin and vimentin significantly increased with increasing age in male patients (> 50 years). In contrast to the considerable rise in vimentin expression in higher grades and stages of the tumor, E-cadherin expression was significantly reduced with tumor stage and grade. The findings of this study reveal that elevated vimentin and reduced E-cadherin are important indicators associated with a poor prognosis for TCC.

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“…Although women have worse survival rates even after adjusting for disease stage at diagnosis, this excess mortality is present only in the first 2 years after diagnosis, thereafter the mortality rate of women is lower than that of men [ 4 , 6 , 11 , 12 ]. According to an analysis of the SEER database between 1990 and 2005, differences in prognostic factors such as age, tumor stage, grade and histological type account only for about 30% of the sex differences in BC mortality [ 11 ], suggesting that other factors such as differences in tumor biology, choice and efficacy of treatments and delay in treatment could contribute to this excess female mortality [ 12 , 13 ].…”

Section: Introductionmentioning

confidence: 99%

Sex differences in treatment patterns for non-advanced muscle-invasive bladder cancer: a descriptive analysis of 3484 patients of the Netherlands Cancer Registry

et al. 2022

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Purpose Bladder cancer (BC) is a common malignancy with well-established differences in incidence, clinical manifestation and outcomes between men and women. It is unknown to what extent disparities in outcomes are influenced by differences in treatment approaches. This paper describes treatment patterns among men and women with muscle-invasive BC focusing on curative treatment (radical cystectomy or trimodal therapy). Methods A retrospective population-based cohort study was performed with data from the Netherlands Cancer Registry. All patients newly diagnosed with muscle-invasive, non-advanced BC (MIBC, cT2-4a, N0/X, M0/X) in the years 2018, 2019 and 2020 were identified. Patient and tumor characteristics and initial treatment were compared between men and women with descriptive statistics and multivariable logistic regression analyses. Results A total of 3484 patients were diagnosed with non-advanced MIBC in 2018–2020 in the Netherlands, of whom 28% were women. Women had higher T-stage and more often non-urothelial histology. Among all strata of clinical T-stage, women less often received treatment with curative intent (radical cystectomy [RC] or trimodality treatment). Among RC-treated patients, women more often received neoadjuvant treatment (except for cT4a disease). After adjustment for pre-treatment factors, odds ratios were indicative of women having lower probability of receiving curative treatment and RC specifically, and higher probability to receive NAC when treated with RC then men, although not statistically significant. Conclusions Considerable differences in treatment patterns between men and women with MIBC exist. A more considerate role of the patient’s sex in treatment decisions could help decrease these differences and might mitigate disparities in outcomes.

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Gender Differences in Urothelial Bladder Cancer: Effects of Natural Killer Lymphocyte Immunity

Cited by 6 publications

References 245 publications

Biomarkers to assess the risk of bladder cancer in patients presenting with haematuria are gender-specific

Biomarkers to assess the risk of bladder cancer in patients presenting with haematuria are gender-specific

The Immunohistochemical Staining of Vimentin and E-Cadherin in Bladder Cancer Patients Infected with Hepatitis C Virus

Sex differences in treatment patterns for non-advanced muscle-invasive bladder cancer: a descriptive analysis of 3484 patients of the Netherlands Cancer Registry

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