Upregulated LOX and increased collagen content associated with aggressive clinicopathological features and unfavorable outcome in oral squamous cell carcinoma.

Abstract

Collagen is a core protein that maintains the homeostasis of the extracellular matrix (ECM), and its dysregulation in human cancers has attracted increasing attention. In tumors, increased lysyl oxidase (LOX)-catalyzed collagen cross-linking plays a critical role in collagen dysregulation. However, the expression patterns of LOX and collagen and their clinicopathological significance in oral squamous cell carcinoma (OSCC) have not been well established. The LOX mRNA expression in OSCC was measured by RT-PCR and bioinformatics analysis. LOX protein expression and total collagen content were identified by immunohistochemistry or Masson's trichrome staining in a retrospective cohort of primary OSCC samples, respectively. Moreover, the associations between LOX and collagen expression and various clinicopathological parameters or patient survival were assessed. LOX mRNA was overexpressed in OSCC samples. Higher expression of LOX, collagen content or co-overexpression of LOX and collagen was significantly associated with aggressive clinicopathological features. Importantly, aberrant expression of LOX, collagen content, or both were markedly correlated with decreased overall and disease-free survival (P < 0.05). Moreover, univariate and multivariate Cox models analyses indicated that LOX, collagen content or their combination could serve as an independent prognostic predictor for OSCC patients. ROC analysis further revealed that the combination of LOX and collagen was superior to parameter alone as a prognostic predictor. Our findings reveal that elevated LOX and collagen content significantly corelate with aggressiveness and worse prognosis in OSCC.