Isocitrate Dehydrogenase 1 Is a Novel Plasma Biomarker for the Diagnosis of Non–Small Cell Lung Cancer

Isocitrate Dehydrogenase 1 Is a Novel Plasma Biomarker for the Diagnosis of Non–Small Cell Lung Cancer

1. Nan Sun,
2. Zhaoli Chen,
3. Fengwei Tan,
4. Baihua Zhang,
5. Ran Yao,
6. Chengcheng Zhou,
7. Jiagen Li,
8. Yibo Gao,
9. Ziyuan Liu,
10. Xiaogang Tan,
11. Fang Zhou,
12. Max Y.F He,
13. Kang Shao,
14. Ning Li,
15. Bin Qiu,
16. Jian Sun,
17. Yue Yu,
18. Suya Wang,
19. Yuda Zhao,
20. Xuejiao Shi, and
21. Jie He

+ Author Affiliations

1. Authors' Affiliation: Department of Thoracic Surgery, Cancer Institute and Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China

1. Corresponding Author:
   Jie He, Department of Thoracic Surgery, Cancer Institute and Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, 17 Panjiayuan Nanli, Chaoyang District, PO Box 2258, Beijing 100021, PR China. Phone: 86-10-87788798; Fax: 86-10-67709698; E-mail: prof.jiehe@gmail.com

Abstract

Purpose: Effective biomarkers for the diagnosis of non–small cell lung cancer (NSCLC) are needed. We previously showed that isocitrate dehydrogenase 1 (IDH1) is significantly increased in NSCLC tumors. This study aimed to examine the plasma levels of IDH1 in a large patient population to evaluate its effectiveness in NSCLC diagnosis.

Experimental Design: The plasma levels of IDH1, CA125, Cyfra21-1, and CEA were assayed by ELISA. Blood samples were obtained from 1,422 participants (943 patients with NSCLC and 479 healthy controls). The samples were randomly divided into a training set and a test set. Receiver operating characteristic and binary logistic regression analyses were applied to evaluate diagnostic efficacy and establish diagnostic mathematical models.

Results: Plasma IDH1 levels were significantly higher in patients with NSCLCs than in healthy controls (P < 0.001). The diagnostic use of IDH1 in lung adenocarcinoma [area under curve (AUC): 0.858 and 0.810; sensitivity: 77.1% and 76.2%; specificity: 82.9% and 76.6%; in the training set and test set, respectively] was significantly greater than that of CA125, Cyfra21-1, or CEA (P < 0.001). The model combining IDH1 with CEA, CA125, and Cyfra21-1 was more effective for lung adenocarcinoma diagnosis than IDH1 alone (sensitivity and specificity in the training set: 75.8%, 89.6%; test set: 86.3%, 70.7%). In addition, the plasma levels of IDH1 could contribute to the diagnostic model of lung squamous cell carcinoma.

Conclusions: IDH1 can be used as a plasma biomarker for the diagnosis of NSCLCs, particularly lung adenocarcinoma, with relatively high sensitivity and specificity. Clin Cancer Res; 19(18); 5136–45. ©2013 AACR.

Footnotes

• Note: Supplementary data for this article are available at Clinical Cancer Research Online (http://clincancerres.aacrjournals.org/).

• Received January 7, 2013.
• Revision received June 25, 2013.
• Accepted June 28, 2013.

• ©2013 American Association for Cancer Research.