Mercedes Herrera, Alberto Berral-González, Igor López-Cade, Cristina Galindo-Pumariño, Santiago Bueno-Fortes, Manuel Martín-Merino, Alfredo Carrato, Alberto Ocaña, Carolina De La Pinta, Ana López-Alfonso, Cristina Peña, et al. Cancer-associated fibroblast-derived gene signatures determine prognosis in colon cancer patients

Molecular Cancer. 2021

 "New gene signatures derived from tumor-associated fibroblasts as biomarkers with prognostic value in colon cancer patients" - Dra. Cristina Peña -

Summary:

Background: The crosstalk between malignant cells and other cells in the tumor microenvironment, orchestrated by Cancer-Associated Fibroblasts (CAFs), regulates many aspects of tumorogenesis. Extensive evidence supports the biological relevance of CAFs' heterogeneity and their derived exosomes in the progression of colon tumors. They are decisive factors in the survival of colon cancer patients.

Methods: CAF-related signatures were derived by microarray analysis data from primary established CAFs and normal fibroblasts and by deregulated potential target genes of noncoding RNAs differentially identified by NGS in CAF-derived exosomes. The prognostic value of these signatures was assessed in a series of 1,235 colon cancer patients by means of various bioinformatic approaches.

Results: Our data show that CAF-derived signatures are associated with patients with shorter overall survival. Interestingly, the different signatures studied showed similar prognostic value, indicating the clinical value of CAF deregulation and CAFs/tumor/stromal cells crosstalk mediated by exosomes as coordinators of tumor progression. Moreover, the prognostic value of CAF-derived signatures showed a higher risk value for those patients at advanced tumor stage or "Consensus Molecular Subtype" classification 4.

Conclusions: The identified CAF-derived signatures with prognostic value in colon cancer patients confirm the role of CAF-derived exosomes in tumor progression. They identify new prognostic biomarkers for setting up tailored therapies based on molecular characteristics of colon tumors, which improves patients' survival.

Why do you highlight this publication?

Clinical decisions are based on the usual histological and clinical parameters that do not accurately predict the biological behavior of histologically equal tumors. The risk of recurrence of colon cancer is a critical factor in correctly setting up therapeutic guidelines, which highlights the importance of studying prognosis and predictive biomarkers. The new biomarkers described in this study classify patients on the basis of tumor microenvironment differences and define those pathological events at the molecular and cell level associated with patients' survival. Our results emphasize ongoing efforts to decipher cancer-associated fibroblasts biomarkers in order to advance prognosis and chemotherapeutic responses' heterogeneity and to improve patients' survival by tailoring therapies based on specific biological characteristics of colon tumors.

Dra. Cristina Peña

MOLECULAR EPIDEMIOLOGY AND PREDICTIVE MARKERS IN CANCER GROUP. IRYCIS

Diagram of the study and future perspectives. Created with BioRender.com

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