Work

Exploration of circulating proteins associated with tumor stromal content using matched serum and tissue samples from patients with colon cancer

Year: 2026

Type: article

Abstract: Introduction: Liquid biopsies provide a source of biomolecules that allow tumor characterization. Increasing evidence shows that the tumor microenvironment (TME) plays a central role in behavior of colon cancer. This study assessed which proteins in the circulation correlate with tumor stromal content through analysis of serum and corresponding tissue samples from patients with colon cancer. A broad set of circulating proteins is quantified, ranging from common apolipoproteins, transport and complement factors, to key factors from interconnected stromal pathways such as coagulation and acute phase inflammation. Materials and methods: The cohort consisted of 97 patients with colon cancer and 50 control individuals who all underwent colonoscopy. Targeted mass spectrometry was applied to quantify 156 serum proteins via their surrogate peptides and corresponding internal standards. Matching solid tumor tissue slides from all 97 patients were used to determine the Tumor-Stroma Ratio (TSR). Serum protein levels were compared between stroma-high and stroma-low tumors, resulting in a subset of discriminating proteins. Composite protein scores were evaluated in multivariable Cox models. Results: Four serum proteins differed significantly between stroma-high and stroma-low tumors, all showing elevated levels in stroma-high patients, including complement-related proteins (C2, factor B, and C1r subcomponent-like protein) and the coagulation-related vitamin K-dependent protein S. This resulted in a composite Stromal Protein Score that may capture TME-driven variations. The Stromal Protein Score was significantly different between stroma-high and stroma-low patients (adjusted p < 0.001). Conclusion: Our data indicate that stroma-high tumors are associated with systemic alterations in complement and coagulation-related proteins. The results encourage further development of liquid biopsy-based protein profiling approaches, aiming for clinical implementation as a non-invasive strategy for TME-informed risk stratification and treatment monitoring in colon cancer.

Source: The Journal of Liquid Biopsy

DOI: 10.1016/j.jlb.2026.100688