Evidence of the Link between Stroma Remodeling and Prostate Cancer Prognosis

Simple Summary Prostate cancer (PCa) is among the most common cancers. While PCa is frequently diagnosed in elderly men as a slow-growing, low-risk disease, in about 10-15% of cases, it can become a life-threatening danger. Unfortunately, biomarkers able to discriminate indolent prostatic tumors from aggressive forms are lacking, and watchful waiting remains one of the best options. However, available data support the hypothesis that distinctive biological characteristics of PCa stroma can contribute to cancer progression in a clinically relevant way. According to the current view, tissue alterations induced by tumor growth affect both metabolism of resident normal cells and composition of the extracellular matrix and are able also to recruit cells from circulation. Here, we seek to respond to the challenge of identifying stroma-associated biomarkers that may be relevant to assist prognostic decisions in PCa patients.Abstract Prostate cancer (PCa), the most commonly diagnosed cancer in men worldwide, is particularly challenging for oncologists when a precise prognosis needs to be established. Indeed, the entire clinical management in PCa has important drawbacks, generating an intense debate concerning the possibility to individuate molecular biomarkers able to avoid overtreatment in patients with pathological indolent cancers. To date, the paradigmatic change in the view of cancer pathogenesis prompts to look for prognostic biomarkers not only in cancer epithelial cells but also in the tumor microenvironment. PCa ecology has been defined with increasing details in the last few years, and a number of promising key markers associated with the reactive stroma are now available. Here, we provide an updated description of the most biologically significant and cited prognosis-oriented microenvironment biomarkers derived from the main reactive processes during PCa pathogenesis: tissue adaptations, inflammatory response and metabolic reprogramming. Proposed biomarkers include factors involved in stromal cell differentiation, cancer-normal cell crosstalk, angiogenesis, extracellular matrix remodeling and energy metabolism.