Identification of α-enolase as an autoantigen in lung cancer: Its overexpression is associated with clinical outcomes

Gee Chen Chang, Ko Jiunn Liu, Chia Ling Hsieh, Tsai Shu Hu, Suparat Charoenfuprasert, Hsiung Kun Liu, Kwen Tay Luh, Li Han Hsu, Chew Wen Wu, Chou Chik Ting, Chih Yi Chen, Kun Chieh Chen, Tsung Ying Yang, Teh Ying Chou, Wen Hua Wang, Jacqueline Whang-Peng, Neng Yao Shih

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Abstract

Purpose: Although existence of humoral immunity has been previously shown in malignant pleural effusions, only a limited number of immunogenic tumor-associated antigens (TAA) have been identified and associated with lung cancer. In this study, we intended to identify moreTAAs in pleural effusion - derived tumor cells. Experimental Design: Using morphologically normal lung tissues as a control lysate in Western blotting analyses, 54 tumor samples were screened with autologous effusion antibodies. Biochemical purification and mass spectrometric identification of TAAs were done using established effusion tumor cell lines as antigen sources. We identified a p48 antigen as α-enolase (ENO1). Semiquantitative immunohistochemistry was used to evaluate expression status of ENO1 in the tissue samples of 80 patients with non-small cell lung cancer (NSCLC) and then correlated with clinical variables. Results: Using ENO1-specifc antiserum, up-regulation of ENO1 expression in effusion tumor cells from 11 of 17 patients was clearly observed compared with human normal lung primary epithelial and non-cancer-associated effusion cells. Immunohistochemical studies consistently showed high level of ENO1 expression in all the tumors we have examined thus far. Log-rank and Cox's analyses of ENO1 expression status revealed that its expression level in primary tumors was a key factor contributing to overall- and progression-free survivals of patients (P <0.05). The same result was also obtained in the early stage of NSCLC patients, showing that tumors expressing relatively higher ENO1 level were tightly correlated with poorer survival outcomes. Conclusions: Our data strongly support a prognostic role of ENO1 in determining tumor malignancy of patients with NSCLC.

Original languageEnglish
Pages (from-to)5746-5754
Number of pages9
JournalClinical Cancer Research
Volume12
Issue number19
DOIs
Publication statusPublished - Oct 1 2006
Externally publishedYes

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ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Chang, G. C., Liu, K. J., Hsieh, C. L., Hu, T. S., Charoenfuprasert, S., Liu, H. K., Luh, K. T., Hsu, L. H., Wu, C. W., Ting, C. C., Chen, C. Y., Chen, K. C., Yang, T. Y., Chou, T. Y., Wang, W. H., Whang-Peng, J., & Shih, N. Y. (2006). Identification of α-enolase as an autoantigen in lung cancer: Its overexpression is associated with clinical outcomes. Clinical Cancer Research, 12(19), 5746-5754. https://doi.org/10.1158/1078-0432.CCR-06-0324