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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

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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.

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Abbreviations

NPC:

Nasopharyngeal carcinoma

TMA:

Tissue microarray

DFS:

Disease free survival

OS:

Overall survival

IHC:

Immunohistochemistry

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Acknowledgments

We are grateful to the Ear, Nose and Throat (ENT) department at Xiangya Hospital, the Second Xiangya Hospital and the Tumor Hospital of Hunan Province for providing our NPC samples. This work was supported by the National Natural Science Foundation of China (Grant Nos. 30871282, 30871365, 81172189, 81071644, 30971147, 81171930, 81071820), the 111 Project (Grant No. 111-2-12), the Natural Science Foundation of Hunan Province (Grant Nos. 10JJ7003), the Fok Ying Tong Education Foundation (121036) and the Fundamental Research Funds for the Central Universities (2011JQ020).

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We declare that we have no conflicts of interest.

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Authors and Affiliations

  1. Cancer Research Institute, Disease Genome Research Center, Key Laboratory of Carcinogenesis of Ministry of Health, Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Central South University, Changsha, 410078, China

    Zhaoyang Zeng, Yanhong Zhou, Fang Liang, Minghua Wu, Ke Tang, Li Cao, Xiaoling Li, Wei Xiong & Guiyuan Li

  2. Department of Medical Laboratory Science, Xiangya School of Medicine, Central South University, Changsha, 410013, China

    Wenling Zhang

  3. Department of Pathology, Second Xiangya Hospital, Central South University, Changsha, 410011, China

    Songqing Fan

  4. Department of Medicine, National Jewish Health, 1400 Jackson Street, Denver, CO, 80206, USA

    Jieru Wang

  5. Department of Laboratory Medicine and Pathology and Masonic Cancer Center, University of Minnesota, Minneapolis, MN, 55455, USA

    Jianbo Yang

  6. Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Third Xiangya Hospital, Central South University, Changsha, 410011, China

    Xiayu Li

  7. Xiangya Hospital, Central South University, Changsha, 410078, China

    Donghai Huang

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  1. Wenling Zhang
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  2. Zhaoyang Zeng
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  12. Li Cao
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  13. Xiaoling Li
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Correspondence to Wei Xiong or Guiyuan Li.

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10735_2012_9392_MOESM1_ESM.tif

Supplementary Fig 1 Our cDNA microarray data was reanalyzed using SAM software. The results suggested that there were 488 down-regulated genes and 278 up-regulated genes in NPC. Among these differentially expressed genes, ALK1 and TGFβR2 were both down-regulated in NPC. (TIFF 761 kb)

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Zhang, W., Zeng, Z., Fan, S. et al. 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. J Mol Hist 43, 297–306 (2012). https://doi.org/10.1007/s10735-012-9392-4

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