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. 2018 May;12(5):602-610.
doi: 10.1002/1878-0261.12182. Epub 2018 Mar 25.

IDH2 is a novel diagnostic and prognostic serum biomarker for non-small-cell lung cancer

Jiang-Jiang Li  1   2   3   4 , Ruilei Li  5 , Wenxiang Wang  6 , Baihua Zhang  6 , Xin Song  5 , Chunfang Zhang  7 , Yang Gao  7 , Qianjin Liao  8 , Ya He  1   2   3 , Shuo You  9 , Zheqiong Tan  1   2   3 , Xiangjian Luo  1   2   3 , Yueshuo Li  1   2   3 , Min Tang  1   2   3 , Xinxian Weng  1   2   3 , Wei Yi  1   2   3 , Shifang Peng  10 , Shaohui Liu  11 , Ying Tan  11 , Ann M Bode  12 , Ya Cao  1   2   3   4   13
Affiliations

IDH2 is a novel diagnostic and prognostic serum biomarker for non-small-cell lung cancer

Jiang-Jiang Li et al. Mol Oncol. 2018 May.

Abstract

Lung cancer is the most common leading cause of cancer-related death worldwide. Late diagnosis contributes to a high mortality rate and poor survival of this cancer. In our previous study, we found that IDH2 polymorphism rs11540478 is a risk factor for lung cancer. Here, we examined IDH2 protein expression in culture medium in which two non-small-cell lung cancer (NSCLC) cell lines, H460 and A549, were growing. We found that the IDH2 protein was elevated in the culture supernatant fraction in a time- and cell number-dependent manner. Next, we used ELISA methods to examine IDH2 protein level in serum from patients with NSCLC and healthy controls. We found that IDH2 protein levels in serum could distinguish NSCLC patients from healthy controls with an AUC (area under the curve) of 0.83 (95% confidence interval = 0.79-0.88). The IDH2 level was decreased in serum from NSCLC postsurgical patients compared with the paired presurgical serum. High serum IDH2 levels appear to correlate with poor survival in patients with NSCLC. These results suggest that IDH2 levels in the serum could be a new effective biomarker for the diagnosis and prognosis of NSCLC.

Keywords: IDH2; non-small-cell lung cancer; serum biomarker.

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Figures

Figure 1
Figure 1
IDH1/2 concentration in the culture medium of cancer cells. The concentration of the IDH2 protein in the culture medium of cancer cells was determined by ELISA methods, and culture medium without cells was used as a control. (A) IDH2 concentration in the culture medium of H460 and A549 lung cancer cells at different culture time points. (B) IDH2 concentration in the culture medium of different numbers of H460 and A549 lung cancer cells. (C) IDH2 concentration in the culture medium of HCT116 and HT29 colon cancer cell lines. (D) IDH1 concentration in the culture medium of H460 and A549 lung cancer cells. The asterisks (*, **) indicate a significant (P < 0.05, P < 0.01, respectively) difference.
Figure 2
Figure 2
Levels of IDH2 in serum from patients with NSCLC and healthy controls. IDH2 concentration was measured in serum from patients with lung cancer adenocarcinoma (ADC), squamous cell carcinoma (SCC),and healthy controls in training set (A), test set (B), and whole set (C). Statistical significance was determined by the Mann–Whitney U‐test.
Figure 3
Figure 3
ROC curve analyses using IDH2 to differentiate NSCLC cases from healthy controls. (A–C) ROC curves of patients with lung cancer adenocarcinoma (ADC), squamous cell carcinoma (SCC), and healthy controls in training set (A), test set (B), and patients with NSCLC in whole set (C).
Figure 4
Figure 4
Expression of IDH2 in serum from pre‐ and postsurgical patients with NSCLC. (A) The level of IDH2 in serum was determined by ELISA methods in the same patients with NSCLC before and after surgery (n = 29). (B) The level of IDH2 in serum was determined by ELISA methods in healthy control subjects and in the same patients with NSCLC before and after surgery. Statistical significance was determined by the Mann–Whitney U‐test.
Figure 5
Figure 5
Kaplan–Meier survival analysis of patients with NSCLC based on serum IDH2 levels. The medium of serum IDH2 (12.52 ng·mL−1) was set as the cutoff value. The overall survival rate of NSCLC patients with high serum IDH2 level (n = 35) was significantly lower than patients with low serum IDH2 level (n = 91; P = 0.042; log‐rank test).
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