Therapeutic advances in medical oncology · 2026
Serum levels of the C-terminal pro-peptide of type V collagen have prognostic potential and are associated with a normal subtype of desmoplasia in a retrospective cohort of patients with esophagogastric cancer.
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Doeve Benthe H, Nissen Neel I, Weeda Vera, Dings Mark P G, Meijer Sybren L, van Laarhoven Hanneke W M, Bijlsma Maarten F, Willumsen Nicholas
Аннотация
BACKGROUND: The role of stroma in esophagogastric cancer is ambiguous, with both tumor-promoting and tumor-restrictive properties. Several non-invasive biomarkers of stroma have recently been identified, but their relationship with stromal composition and clinical outcome in esophagogastric cancer remains insufficiently understood.
OBJECTIVES: We aimed to investigate the association of serum stromal biomarkers with overall survival and stroma composition in esophagogastric cancers.
DESIGN: Eleven stromal biomarkers were retrospectively measured in pre-treatment serum of 78 patients with esophagogastric cancer and 11 healthy controls.
METHODS: Elastic net Cox regression was applied to associate serum concentration of stromal biomarkers with overall survival in patients with esophagogastric cancer. These associations were later confirmed with Kaplan-Meier curves and multivariate Cox regression analysis. RNA-sequencing was performed on 17 matched tumor biopsies and an independent validation cohort of 100 pre-treatment biopsies to explore the relation between stromal biomarker and stromal subtype.
RESULTS: This study revealed that serum formation fragment of collagen V as a stromal biomarker was high in patients with esophagogastric cancer compared to healthy subjects. A high serum concentration of the formation fragment of collagen V was independently prognostically favorable in patients with esophagogastric cancer. The formation of collagen V correlated with a distinct normal stroma subtype in the matched tumor biopsies. A gene signature specific for the formation fragment of collagen V was also independently prognostically favorable and correlated with a normal stroma subtype in the validation cohort.
CONCLUSION: In conclusion, the formation of collagen V reflects a distinct normal stroma subtype in patients with esophagogastric cancer that associates with favorable outcomes.
OBJECTIVES: We aimed to investigate the association of serum stromal biomarkers with overall survival and stroma composition in esophagogastric cancers.
DESIGN: Eleven stromal biomarkers were retrospectively measured in pre-treatment serum of 78 patients with esophagogastric cancer and 11 healthy controls.
METHODS: Elastic net Cox regression was applied to associate serum concentration of stromal biomarkers with overall survival in patients with esophagogastric cancer. These associations were later confirmed with Kaplan-Meier curves and multivariate Cox regression analysis. RNA-sequencing was performed on 17 matched tumor biopsies and an independent validation cohort of 100 pre-treatment biopsies to explore the relation between stromal biomarker and stromal subtype.
RESULTS: This study revealed that serum formation fragment of collagen V as a stromal biomarker was high in patients with esophagogastric cancer compared to healthy subjects. A high serum concentration of the formation fragment of collagen V was independently prognostically favorable in patients with esophagogastric cancer. The formation of collagen V correlated with a distinct normal stroma subtype in the matched tumor biopsies. A gene signature specific for the formation fragment of collagen V was also independently prognostically favorable and correlated with a normal stroma subtype in the validation cohort.
CONCLUSION: In conclusion, the formation of collagen V reflects a distinct normal stroma subtype in patients with esophagogastric cancer that associates with favorable outcomes.