Mucinous metaplasia in Pten conditional knockout mice and mucin family genes as prognostic markers for prostate cancer

Abstract

Aims: 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. Main methods: 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. Key findings: 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. Significance: 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.