Isocitrate dehydrogenase 1 is a novel plasma biomarker for the diagnosis of non-small cell lung cancer

Clin Cancer Res. 2013 Sep 15;19(18):5136-45. doi: 10.1158/1078-0432.CCR-13-0046.


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.

Publication types

  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / blood
  • Adenocarcinoma / diagnosis*
  • Adult
  • Aged
  • Aged, 80 and over
  • Antigens, Neoplasm / blood
  • Area Under Curve
  • Biomarkers, Tumor / blood*
  • CA-125 Antigen / blood
  • Carcinoembryonic Antigen / blood
  • Carcinoma, Non-Small-Cell Lung / blood
  • Carcinoma, Non-Small-Cell Lung / diagnosis*
  • Carcinoma, Squamous Cell / blood
  • Carcinoma, Squamous Cell / diagnosis*
  • Case-Control Studies
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Follow-Up Studies
  • Humans
  • Isocitrate Dehydrogenase / blood*
  • Keratin-19 / blood
  • Lung Neoplasms / blood
  • Lung Neoplasms / diagnosis*
  • Male
  • Membrane Proteins / blood
  • Middle Aged
  • Neoplasm Staging
  • Prognosis
  • ROC Curve


  • Antigens, Neoplasm
  • Biomarkers, Tumor
  • CA-125 Antigen
  • Carcinoembryonic Antigen
  • Keratin-19
  • MUC16 protein, human
  • Membrane Proteins
  • antigen CYFRA21.1
  • Isocitrate Dehydrogenase
  • IDH1 protein, human