Expression of APOA4 gene in urothelial bladder carcinoma: a potential diagnostic immunohistochemical biomarker
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Abstract
Objective: To investigate the immunohistochemical expression of Apolipoprotein A-IV (APOA4) as a potential diagnostic and prognostic biomarker in urothelial bladder carcinoma (UBC).
Methods: This cross-sectional study was conducted from January 2020 to December 2022, at the Institute of Pathology and Diagnostic Medicine, Khyber Medical University, Peshawar, Pakistan. Formalin-fixed paraffin-embedded tumor tissues were stained with hematoxylin and eosin for histopathological classification and with APOA4 antibody for immunohistochemistry (IHC). Stained sections were evaluated microscopically using a blinded method, and APOA4 expression was quantified with a semi-quantitative Histoscore (0–300). Statistical analysis was performed using the Mann-Whitney U test, with diagnostic validity assessed by ROC curve analysis.
Results: A total of 121 participants were included (67 UBC patients, 54 controls). Among UBC cases, 31 (46%) were non-invasive low-grade papillary, 24 (36%) were non-invasive high-grade papillary, and 11 (16%) were invasive urothelial carcinoma. The mean proportion of APOA4-positive cells was 44% in cases versus 9% in controls, with mean Histoscores of 76 and 10, respectively (p<0.0001). ROC analysis showed an AUC of 0.79, with sensitivity and specificity varying according to cutoff thresholds.
Conclusion: APOA4 expression was significantly higher in UBC tissues compared to controls, with increasing expression correlating with tumor grade and stage. These findings suggest that APOA4 has potential diagnostic and prognostic value in UBC, warranting further validation in larger, prospective studies.
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