Biomarkers for Precision Urothelial Carcinoma Diagnosis: Current Approaches and the Application of Single-Cell Technologies

Hong, Michelle; He, George; Goh, Siting; Low, Albert; Tay, Kae Jack; Lim, Tony Kiat Hon; Yeong, Joe; Khor, Li Yan; Lim, Tong Seng

doi:10.3390/cancers13020260

Cited by 19 publications

(16 citation statements)

References 103 publications

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“…Another surprising finding was observed regarding the tumor grade. We detected higher sensitivity for low-grade tumors (G1) compared to UC (10%-43%), 9 quantitative and qualitative NMP22 test (48%; SD = 25.7), and BTA test (42.9%; SD = 5.7). 15 The sensitivity for low-grade tumors was analogous to that of the fluorescent-based probes.…”

Section: Discussionmentioning

confidence: 79%

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AHNAK2 Urinary Protein Expression as Potential Biomarker for Bladder Cancer Detection: A Pilot Study

Komina¹,

Petruševska²,

Jovanović³

et al. 2022

Turkish Journal of Urology

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Objective: This study aimed to measure the AHNAK2 urinary levels in bladder cancer patients. Material and methods: This prospective case–control study enrolled 67 participants between January and March 2019 and were categorized into bladder cancer group (n = 37), with histologically proven bladder cancer, and control group (n = 30), with histologically verified benign lesions or with no bladder cancer indication during follow-up. Urine samples of 15 mL were collected in the mid-morning before cystoscopy/surgery and an enzyme-linked immunosorbent assay was performed as per the manufacturer’s protocol. Bladder malignancies were classified according to the World Health Organization Tumor Classification. Group’s associations were evaluated with the Student t -test, Spearman’s rank correlation, and Mann–Whitney U test, while receiver operating curve was plotted for assessing the test’s performance. Results: Mean age of the bladder cancer group was 66.41 years (standard deviation = 10.04, range = 43-82 years) and the control group was 59.67 years (standard deviation = 10.44, range = 38-77 years). All bladder cancers were of the urothelial histotype, with the following pT distribution: pTa/papillary urothelial neoplasm of low malignant potential (n = 19; 28.4%), Primary tumor (pT) in situ (n = 4; 6%), pT1 (n = 7; 10.4%), and pT≥2 (n = 7; 10.48%). Mean AHNAK2 levels were higher in bladder cancer patients 49.08 pg/mL (standard deviation = 114.91) compared to controls 5.28 pg/mL (standard deviation = 6.65), P < .05). Significant differences were noted between non-invasive bladder cancer (n = 23; mean = 7.14 pg/mL; standard deviation = 7.26) and invasive bladder cancer (n = 14; mean = 117.99 pg/mL; standard deviation = 168.08) and between non-muscle invasive bladder cancer (mean = 23.19 pg/mL; standard deviation = 66.93) and muscle-invasive bladder cancer (mean = 160.05 pg/mL; standard deviation = 199.65) ( P < .001). The result of the assays was given as follows: sensitivity: 64.19%, specificity: 66.67%, positive predictive value: 22.07%, negative predictive value: 92.37%, area under curve: 0.695, and 95% CI: 0.57-0.82. Conclusion: AHNAK2 protein could be used as bladder cancer surveillance biomarker. The inclusion of AHNAK2 levels in stratification nomograms might reduce the number of unnecessary cystoscopies.

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Section: Discussionmentioning

confidence: 79%

“… 8 While UC is sensitive to high-grade lesions, it has limited diagnostic accuracy in low-grade bladder tumors. 9 Moreover, its interpretation is affected by various factors including collection procedure, low cellular yield, the presence of urinary infections, and interobserver variability. 10 …”

Section: Introductionmentioning

confidence: 99%

AHNAK2 Urinary Protein Expression as Potential Biomarker for Bladder Cancer Detection: A Pilot Study

Komina¹,

Petruševska²,

Jovanović³

et al. 2022

Turkish Journal of Urology

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“…3 It has a low sensitivity for detecting urothelial carcinoma but still performed as it is non-invasive and relatively inexpensive. 4 In patients with bladder cancer, the diagnostic accuracy is enhanced if cell blocks are made together with the conventional smears. 5 Cell blocks are also useful for special stains and immunohistochemical staining.…”

Section: Original Articlementioning

confidence: 99%

Utility of Cell Block with p53 Immunostain in Diagnosing Urothelial Carcinoma

Nabi¹,

Ali²,

Fatima³

et al. 2022

J Islamabad Med Dental Coll

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Background: Urine cytology is an initial noninvasive screening test done in patients with suspected urothelial carcinoma. The objective of this study was to compare the sensitivity of conventional smear cytology with cell block technique for the diagnosis of malignant cells in urine and to assess the efficacy of p53 immuno-marker in the diagnosis and prognosis of urinary bladder cancer. Methodology: The study was carried out in the department of Histopathology, Pakistan Institute of Medical Sciences(PIMS), Islamabad. Cell blocks and cytology smears and were prepared from urine samples of 80 patients of urothelial carcinoma and p53 stain was applied. Data was analyzed using version 21. Sensitivity of conventional smear and cell block techniques were calculated for both low and high grade urothelial carcinomas. Results:The sensitivity of detecting atypical cells using conventional smear was 31% and 70.6% for low grade and high grade urothelial tumors respectively. The sensitivity increased to 41.4% and 84.3% for low and high grade urothelial carcinomas respectively with cell block technique. Positive p53 stain was seen in 13.8% of cases with low grade tumors and 66.7% cases with high grade tumors. Chi-square test was used to find the association of cytology findings with the histologic grade. Conclusion: Sensitivity of urine cell blocks is higher than the conventional smear method for detecting high grade lesions. It can be used as an efficient non-invasive technique and an adjunct tool for the determination of disease relapse and overall survival in patients. Keywords: Carcinoma, Cytology, P53 Protein, Urine

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“…The main risk factor for bladder cancer is considered occupational exposure to chemicals, water contaminants, and cigarette smoking [ 2 , 3 ]. Urothelial cell carcinoma (UCC) is the most common form of bladder cancer, accounting for more than 90% of diagnosed cases [ 4 ]. UCC begins as superficial bladder carcinomas and progresses heterogeneously with a variable course.…”

Section: Introductionmentioning

confidence: 99%

Phenolic Extract from Extra Virgin Olive Oil Induces Different Anti-Proliferative Pathways in Human Bladder Cancer Cell Lines

et al. 2022

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Regular consumption of olive oil is associated with protection against chronic-degenerative diseases, such as cancer. Epidemiological evidence indicates an inverse association between olive oil intake and bladder cancer risk. Bladder cancer is among the most common forms of cancer; in particular, the transitional cell carcinoma histotype shows aggressive behavior. We investigated the anti-proliferative effects of a phenolic extract prepared from an extra virgin olive oil (EVOOE) on two human bladder cancer cell lines, namely RT112 and J82, representing the progression from low-grade to high-grade tumors, respectively. In RT112, the EVOOE reduced cell viability (IC50 = 240 μg/mL at 24 h), triggering a non-protective form of autophagy, evidenced by the autophagosome formation and the increase in LC-3 lipidation. In J82, EVOOE induced a strong decrease in cell viability after 24 h of treatment (IC50 = 65.8 μg/mL) through rapid and massive apoptosis, assessed by Annexin V positivity and caspase-3 and -9 activation. Moreover, in both bladder cancer cell lines, EVOOE reduced intracellular reactive oxygen species, but this antioxidant effect was not correlated with its anti-proliferative outcomes. Data obtained suggest that the mixture of phenolic compounds in extra virgin olive oil activates different anti-proliferative pathways.

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Biomarkers for Precision Urothelial Carcinoma Diagnosis: Current Approaches and the Application of Single-Cell Technologies

Cited by 19 publications

References 103 publications

AHNAK2 Urinary Protein Expression as Potential Biomarker for Bladder Cancer Detection: A Pilot Study

AHNAK2 Urinary Protein Expression as Potential Biomarker for Bladder Cancer Detection: A Pilot Study

Utility of Cell Block with p53 Immunostain in Diagnosing Urothelial Carcinoma

Phenolic Extract from Extra Virgin Olive Oil Induces Different Anti-Proliferative Pathways in Human Bladder Cancer Cell Lines

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