Prognostic Value of Tumor-stroma Ratio in Oral Squamous Cell Carcinoma: Contribution of Cancer Associated Fibroblasts

Background: The aim of this study is to confirm the prognostic value of the tumor–stroma ratio (TSR) in a large cohort of oral squamous cell carcinoma (OSCC) and further demonstrated the cancer associated fibroblasts (CAFs)-stroma ratio (CSR) served as a critical biomarkers contributed to the prognostic value of TSR Results: The threshold level of TSR value is 50%, which divides patients into high (>50%) and low (<50%) stroma. We examined the TSR on hematoxylin and eosin-stained tissue samples from 581 patients with oral squamous cell carcinoma and 298 cases were included in the high-stroma group. In multivariate analysis, the TSR was identified as an independent prognostic factor for disease-free survival (DFS) (hazard ratio (HR), 2.11; 95% confidence interval (CI), 1.56–2.86; p < 0.001) and oral cancer-specific survival (OCSS) (HR, 2.56, 95% CI, 1.78–3.67; p < 0.001). The interaction term reached statistical significance for histological grade. Multivariate analysis confirmed the discriminative value of the TSR in well differentiated tumors for DFS and OCSS separately (P=0.001, P=0.003). The prognostic value of TSR was not varied by other clinically subgroups. Furthermore, the high-stroma group had a higher Fibroblast Activation Protein (FAP+) CSR and α-Smooth Muscle Actin (α-SMA+) CSR than the low-stroma group (p < 0.001).Conclusion: High-stroma levels indicated a negative consequence and a higher CAFs–stroma ratio than low-stroma levels in OSCC. The TSR is not altered by other clinically elements rendering it a credible histological parameter and informing the rational design of individual cancer management.