Comprehensive analyses of the cancer-associated fibroblast subtypes and their score system for prediction of outcomes and immunosuppressive microenvironment in prostate cancer

Ze Gao ^1,2, Ning Zhang ³, Bingzheng An ¹

⁰Department of Urology, Qilu Hospital of Shandong University, Jinan, 250012, China.

Cancer Cell International +

|

April 5, 2024

View abstract on PubMed

Summary

Cancer-associated fibroblasts (CAFs) have diverse roles in cancer. This study defines CAF subtypes in prostate cancer, developing a scoring system to predict patient outcomes and immunotherapy response across multiple cancer types.

Area Of Science

Oncology
Cancer Biology
Immunology

Background

Cancer-associated fibroblasts (CAFs) exhibit heterogeneity, influencing tumor progression and treatment response.
Single-cell RNA sequencing (scRNA-seq) has revealed CAF molecular subtypes, but their clinical significance in prostate cancer (PCa) remains unclear.

Purpose Of The Study

To investigate the biological and clinical implications of CAF molecular subtypes in prostate cancer.
To develop a prognostic model based on CAF subtypes for PCa and potentially other malignancies.

Main Methods

Prostate cancer cells were treated with fibroblast supernatant to assess functional effects.
Genomic, sequencing, and clinical data from multiple databases (TCGA, MSKCC, CPGEA, GEO) were analyzed.
CAF subtypes and scores were constructed, and their association with progression-free interval (PFI), clinicopathological features, telomere length, and immune infiltration was evaluated.

Main Results

CAF supernatant promoted PCa cell proliferation and invasion.
Six CAF molecular subtypes were identified in PCa, with subtype-specific scores predicting PFI.
High CAF scores correlated with shorter telomeres and an immunosuppressive tumor microenvironment, predicting better response to CTLA4 inhibitors.
The developed model demonstrated utility as a pan-cancer prognostic predictor.

Conclusions

A novel CAF subtype scoring system was developed using integrated scRNA-seq and bulk RNA-seq data, serving as a prognostic factor for PCa and other cancers.
This system aids in distinguishing immune-suppressive mechanisms in PCa, offering insights into predicting immunotherapy response.
The findings support personalized intervention strategies in PCa treatment.

Keywords:

Caner associated fibroblasts Immunotherapy Prostate cancer Tumor microenvironment Tumor progression

Related Concept Videos

The Tumor Microenvironment

Every normal cell or tissue is embedded in a complex local environment called stroma, consisting of different cell types, a basal membrane, and blood vessels. As normal cells mutate and develop into cancer cells, their local environment also changes to allow cancer progression. The tumor microenvironment (TME) consists of a complex cellular matrix of stromal cells and the developing tumor. The cross-talk between cancer cells and surrounding stromal cells is critical to disrupt normal tissue...