Högskolan i Skövde

Prostate cancer (PCa) is the second most common cancer in men worldwide. The non-cancerous PCa tissue is often used as the benign region irrespective of the zone it is collected for biomarker analysis. Signal Transducer and Activator of Transcription 3 (STAT3) is a transcription factor expressed in epithelial and stromal cells controlling the expression of oncogenes with influence on PCa progression and it has been suggested as a prognostic marker for event-free survival. However, zone-specific expression of activated pSTAT3^Ser727 has so far not been investigated. Therefore, this study aimed to: Firstly, validate the non-cancer cores of PCa patients as a representative of normal control for PCa cores. Secondly, investigate the prostate zone-specific expression of pSTAT3^Ser727 in localized hormone naïve PCa. Thirdly, evaluate the prognostic value of zone-specific pSTAT3^Ser727 expression associated with biochemical recurrence (BCR)-free survival using the zone difference approach. Nuclear and cytoplasmic expression of pSTAT3^Ser727 in epithelium and stroma were scored from prostates of bladder cancer patients and localized hormone naïve PCa patients to calculate the H-score. The H-score subtracted value determined its association with BCR-free survival analysed by Kaplan-Meier curves and Cox-regression analysis. Expression of pSTAT3^Ser727 in normal prostates of the bladder cancer patients was not significantly different from the non-cancer core of the PCa patients. Zone-dependent pSTAT3^Ser727 expression was observed in the zones of the prostatic non-cancer core, however, the non-cancer core had a significantly higher expression of pSTAT3^Ser727 than their zone-corresponding cancer core. Kaplan-Meier curves with log-rank test for the cytoplasm of the epithelium showed lower H-score subtracted value associated with shorter time to BCR. H-score subtracted value in the zone was revealed as an independent prognostic marker for BCR-free survival while adjusting for Gleason grade and Pathological T-stage. Conclusively, expression in non-cancer cores from PCa is validated to be represented as a control to the cancer cores, although differences in the zone-specific expression were observed. We showed pSTAT3^Ser727 zone difference expression in the epithelium as an alternative approach to study biomarkers by improving the prognostic value for BCR.