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
Benthe H. Doeve, Neel I. Nissen, Vera Weeda, Mark P. G. Dings, Sybren L. Meijer, Hanneke W. M. van Laarhoven, Maarten F. Bijlsma, Nicholas WillumsenBackground:
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.