title: 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.
abstract: Gene expression profiling had revealed that TGF-β superfamily type I receptor (also known as activin receptor-like kinase-1, ALK1) and TGFβR2 (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 TGFβR2 in NPC progression or in patient outcomes has been reported. This study aims to assess the possible correlations of ALK1 and TGFβR2 expression with NPC progression and their potential prognostic predictive ability in NPC outcomes. ALK1 and TGFβR2 mRNA and protein levels were detected by qRT-PCR and NPC tissue microarray (TMA), which included 742 tissue cores. Both mRNA and protein levels of ALK1 and TGFβR2 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 TGFβR2 proteins (P = 0.000 and 0.003, respectively). In the final logistic regression analysis model, the abnormal expression of ALK1 and TGFβR2 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 TGFβR2 (DFS: P = 0.072, OS: P = 0.045) could predict the prognosis of NPC patients. The positive expression of ALK1 and TGFβR2 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 TGFβR2 may be useful prognostic biomarkers in NPC.
authors.affiliation: Department of Medical Laboratory Science, Xiangya School of Medicine, Central South University, Changsha 410013, China.
authors.forename: Wenling
authors.initials: W
authors.lastname: Zhang
authors.forename: Zhaoyang
authors.initials: Z
authors.lastname: Zeng
authors.forename: Songqing
authors.initials: S
authors.lastname: Fan
authors.forename: Jieru
authors.initials: J
authors.lastname: Wang
authors.forename: Jianbo
authors.initials: J
authors.lastname: Yang
authors.forename: Yanhong
authors.initials: Y
authors.lastname: Zhou
authors.forename: Xiayu
authors.initials: X
authors.lastname: Li
authors.forename: Donghai
authors.initials: D
authors.lastname: Huang
authors.forename: Fang
authors.initials: F
authors.lastname: Liang
authors.forename: Minghua
authors.initials: M
authors.lastname: Wu
authors.forename: Ke
authors.initials: K
authors.lastname: Tang
authors.forename: Li
authors.initials: L
authors.lastname: Cao
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Li
authors.forename: Wei
authors.initials: W
authors.lastname: Xiong
authors.forename: Guiyuan
authors.initials: G
authors.lastname: Li
mesh_terms: D030301:Activin Receptors, Type II / Q000235:genetics*; D000704:Analysis of Variance; D002277:Carcinoma; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D061346:Laser Capture Microdissection; D008297:Male; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D009305:Nasopharynx / Q000378:metabolism* / Q000473:pathology; D011237:Predictive Value of Tests; D011379:Prognosis; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D012367:RNA, Viral / Q000235:genetics; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics*; D012307:Risk Factors; D016019:Survival Analysis; D046888:Tissue Array Analysis
chemical_list: C099537:Epstein-Barr virus encoded RNA 1; D012367:RNA, Viral; D018125:Receptors, Transforming Growth Factor beta; D017346:Protein Serine-Threonine Kinases; C425364:ACVRL1 protein, human; D030301:Activin Receptors, Type II; D000077294:Receptor, Transforming Growth Factor-beta Type II