The tumor coagulome as a potential biological determinant of postsurgical recurrence of oral squamous cell carcinoma.

Abstract

Objectives: The tumor coagulome is an intrinsic characteristic of human tumors and a key determinant of cancer-associated thrombosis (CAT). Oral Squamous Cell Carcinoma (OSCC) establish a local procoagulant state that contributes to a broad range of vascular complications, and potentially also to tumor progression. Recent clinical studies suggest that biomarkers of coagulation might be of interest for predicting postsurgical recurrence of OSCC, but it remains unclear whether specific properties of the coagulome of OSCC are conducive to postsurgical recurrence. We examined this possibility using transcriptomic analyses of OSCC.

Materials and methods: Using bulk RNA-seq data from TCGA and other sources, we explored the link between the coagulome (n = 85 genes) and disease-free survival (DFS) of OSCC with machine-learning. Tumor microenvironment analyses and single-cell RNA-seq analyses were used to address the potential mechanisms that link coagulation and tumor recurrence. We also compared the coagulome of matched primary/recurrent OSCC.

Results: We identified seven coagulation-related genes, either positively (F3, F2, F8 and PROC) or negatively (VWF, SERPING1, BDKRB2) linked to postsurgical recurrence in OSCC at low/intermediate risk, and we validated the model in an independent cohort. We examined their relationship with the tumor microenvironment, suggesting tumor infiltration by T cells as an element of mechanistic explanation. Increased expression of procoagulant genes, such as F3, was noted in recurrent compared to matched primary OSCC.

Conclusion: Our observations suggest that active coagulation shapes the oncological outcome of surgery. Analyzing the tumor procoagulant status might help predict postsurgical recurrence of OSCC.