A plasma protein involved in tumor oxidation and reduction reactions was useful for detecting and excluding lung cancer in more than three quarters of clinical samples evaluated in a large prospective study.
Isocitrate dehydrogenase 1 (IDH1) measurement was associated with a sensitivity of 77.1% and specificity of 76.2% in a training set of samples (n = 712), and 82.9% sensitivity and 76.6% specificity in a second validation or test set (n = 710).
Sensitivity and specificity were generally improved when the protein’s detection was considered in addition to other known or proposed non–small-cell lung cancer (NSCLC) biomarkers, with sensitivities of 75.8% and 86.3% in the training and test sets, respectively, and specificities of 89.6% and 70.7%.
Dr. He Jie
"Some existing NSCLC biomarkers, such as CEA [carcinoembryonic antigen] and Cyfra21-1 [cytokeratin fragment 21-1], have been used in clinical practice, whereas others, such as CA125 [cancer antigen 125], have been recommended for further validation," Dr. Nan Sun and associates reported in the latest issue of Clinical Cancer Research.
"These biomarkers have low sensitivity, ranging from 50% to 60%, with specificities of approximately 90%," said the researchers, of the department of thoracic surgical oncology at the Cancer Institute and Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences in Beijing.
Previous research by the team had shown IDH1 levels were elevated in tumor samples taken from patients with NSCLC (Mol. Cell. Proteomics 2012;11:M111). Their present investigation (Clin. Cancer. Res. 2013; 19: 5136-45) therefore aimed to see if the protein’s measurement could aid in the diagnosis of lung cancer, differentiating between those who did and those who did not have malignant disease.
For their investigation, the team obtained 1,422 blood samples from 943 patients with previously untreated NSCLC and 479 healthy individuals who were seen for routine examinations between 2007 and 2011 at their institution.
The blood samples from the lung cancer patients were taken 3 days prior to their undergoing surgery and IDH1 levels were immediately determined by enzyme-linked immunosorbent assay, while CEA, Cyfra21-1, and CA125 levels were measured with an Elecys immunoassay analyzer.
Median levels of IDH1 were 2.39 U/L higher than those of healthy controls for squamous cell carcinoma cases (n = 489) cases and 1.96 U/L higher for adenocarcinoma cases (n = 454). Additionally, median plasma levels of IDH1 were higher in patients with adenocarcinomas than in those with squamous cell carcinomas (P = .012)
"We have identified IDH1 as an effective plasma biomarker with high sensitivity and specificity in the diagnosis of NSCLC, especially lung adenocarcinoma," senior study investigator Dr. Jie He said in a press release issued by the American Association for Cancer Research. "Based on the present data, IDH1 can be used to detect stage 1 lung cancer,"
The protein might also detect precancerous lesions, but further studies are required to test that hypothesis, said Dr. He. IDH1 might be a good target for NSCLC treatment as it "may be involved in the development of lung cancer."
A multicenter clinical trial is planned to further validate the diagnostic utility of IDH1.
Research funding was provided by the National High Technology Research and Development Program of China, the International Science and Technology Corporation and Exchange Project, the National Natural Science Foundation of China, the Doctoral Fund of Ministry of Education of China, and the Government Health Care Research Foundation for Senior Officials. The authors had no conflicts of interest to disclose.