Gene Expression Profile of Stromal Factors in Cancer-Associated Fibroblasts from Prostate Cancer

Area of Science:

• Oncology
• Cancer Biology
• Prostate Cancer Research

Background:

• The tumor microenvironment, particularly cancer-associated fibroblasts (CAFs), is increasingly recognized for its role in cancer progression and as a source of therapeutic targets.
• Understanding the specific characteristics of CAFs in prostate cancer (PCa) is crucial for developing effective diagnostic and therapeutic strategies.

Purpose of the Study:

• To characterize the distinct phenotypes of CAFs in localized and advanced PCa, comparing them with normal prostate-associated fibroblasts (NAFs) and fibroblasts from benign prostatic hyperplasia (BPH).
• To identify specific gene expression differences in CAFs associated with PCa progression and response to androgen deprivation therapy (ADT).

Main Methods:

• Prospective recruitment of three patient groups: localized PCa, advanced PCa with ADT, and BPH.
• Comprehensive gene expression analysis of 20 stroma-derived factors in fibroblasts from these patient groups.
• Comparison of gene expression profiles to identify significant differences between CAFs and NAFs/BPH fibroblasts, and between ADT-sensitive and ADT-resistant PCa CAFs.

Main Results:

• Localized PCa CAFs showed significantly higher expression of FGF7, IL6, MMP2, and MMP11 compared to NAFs.
• CAFs from ADT-resistant PCa exhibited significantly higher MMP11 and NFκB expression, and lower TGFβ expression compared to CAFs from ADT-sensitive tumors.
• Specific differences in FGF10, IL17RB, and CXCL14 expression were noted between PCa CAFs and BPH fibroblasts.

Conclusions:

• The study defines distinct CAF phenotypes associated with prostate cancer progression.
• Identified CAF markers may serve as potential diagnostic indicators for PCa.
• Characterized CAF profiles could inform the development of novel therapeutic strategies targeting the tumor microenvironment in PCa.