Evaluation of the prognostic value of TGF-β superfamily type I receptor and TGF-β type II receptor expression in nasopharyngeal carcinoma using high-throughput tissue microarrays

Gene expression profiling had revealed that TGF-β superfamily type I receptor (also known as activin receptor-like kinase-1, ALK1) and TGFbR2 (TGF-β type II receptor) were down-regulated in nasopharyngeal carcinoma (NPC) (P\0.05, respectively). However, no study with significantly large clinical samples to address the relevance of ALK1 and TGFbR2 in NPC progression or in patient outcomes has been reported. This study aims to assess the possible correlations of ALK1 and TGFbR2 expression with NPC progression and their potential prognostic predictive ability in NPC outcomes. ALK1 and TGFbR2 mRNA and protein levels were detected by qRTPCR and NPC tissue microarray (TMA), which included 742 tissue cores. Both mRNA and protein levels of ALK1 and TGFbR2 were significantly lower in the cancer tissues compared with the non-cancerous tissues (P\0.05). Epstein-Barr virus small RNA (EBER-1) hybridization signals in NPC showed significant associations with ALK1 and TGFbR2 proteins (P = 0.000 and 0.003, respectively). In the final logistic regression analysis model, the abnormal expression of ALK1 and TGFbR2 were found to be independent contributors to nasopharyngeal carcinogenesis (P = 0.000 and 0.000, respectively). A survival analysis revealed that ALK1 (Disease Free Survival (DFS): P = 0.002, Overall Survival (OS): P = 0.007) and TGFbR2 (DFS: P = 0.072, OS: P = 0.045) could predict the prognosis of NPC patients. The positive expression of ALK1 and TGFbR2 were independent risk factors for DFS and OS in multivariate analyses (DFS: P = 0.001 and 0.420, respectively; OS: P = 0.018 and 0.047, respectively). These results suggest that ALK1 and TGFbR2 may be useful prognostic biomarkers in NPC.