Agradecimentos: We thank David Neal's Uro-Oncology group (CRUK Cambridge Institute, University of Cambridge, UK) for providing the genetically engineered mouse model FFPE samples. The results presented in this article are partly based on data generated by the Cambridge Carcinoma of the Prostate App (CamcAPP) database from the Cancer Research UK Cambridge Institute and the Human Protein Atlas (HPA) (https://www.proteinatlas.org/) database. We would like to thank Editage (www.editage.com) for excellent assistance with English language editing. We thank Carolina Frandsen Pereira da Costa (@Clorofreela_Sci - https://clorofreela.com/) for the great work on the illustration. This article represents part of NJS’ Ph.D. thesis and part of the undergraduate Scientific Research PPX conducted at the Institute of Biosciences of Botucatu, Sao Paulo State University (UNESP), Botucatu, Sao Paulo, Brazil Ver menos

Abstract: This study evaluated the association of mucinous metaplasia (MM) with tumor cell proliferation, androgen receptor (AR) expression and invasiveness in Pten conditional knockout mice and the prognostic value of MM markers for patients with PCa. Prostatic lobes samples from genetic engineered mouse model Ptenf/f and Pb-Cre4/Ptenf/f were submitted for histopathological analysis and tissue expression of AR, the proliferation marker Ki67, alpha-smooth muscle actin, and laminin. RNAseq data of prostatic lobes samples were analyzed searching for MM gene expression patterns. We also investigated gene and protein expression related to MM in human PCa public databases. All knockout animals analyzed showed at least one area of stroma-invading MM, which was absent in the control animals. The tumoral regions of MM showed a proliferative index 5 times higher than other tumoral areas and low expression of the AR (less than 20% of the cells were AR-positive). Disrupted basement membrane areas were observed in MM. The mouse and human PCa transcriptomes exhibited increased expression of the MM markers such as MUC1, MUC19, MUC4, MUC5AC, MUC5B, and TFF3. Gene expression profile was associated with castration-resistant prostate cancer (CRPC) and with a lower probability of freedom from biochemical recurrence. The expression of goblet cell genes, such as MUC1, MUC5AC, MUC5B, and TFF3 have significant prognostic value for PCa patients and represent another class of potential therapeutic targets Ver menos