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

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.

Proteomics biomarkers for non-small cell lung cancer

“…Blockage of HSP27 or HSP27 signaling might prevent lung squamous cancer cells from invasion and metastasis. Similar association with poor overall survival was identified in isocitrate dehydrogenase 1 (IDH1) [34,61].…”

Non-small-cell lung cancers: a heterogeneous set of diseases

“…For example, high-throughput screens using established short hairpin RNA (shRNA) libraries have identified genes that cause synthetic lethality with common oncogenic events, such as KRAS-activating mutations or p53 inactivation, leading to potential new treatment targets, such as TANK-binding kinase 1 (TBK1) 32 . Similarly, the application of mass spectrometry to metabolomic, proteomic and phosphokinase profiling, as well as single cell time-of-flight mass cytometry (cyTOF), have led to numerous new findings, including the discovery of recurrent aberrations such as the ROS1 fusions and the potential diagnostic or prognostic marker isocitrate dehydrogenase 1 (IDH1) 17,33,34 . Such advances in high-throughput technology are promoting rapid advances in our understanding of NSCLC biology and, ultimately, will help to determine how NSCLC develops, spreads and can be better treated.…”

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

“…Analysis showed an AUC of 0.83 (Fig. A), which is better than that of current clinically used biomarkers, including CA125, Cyfra21‐1, and CEA, and similar to that of IDH1 (Sun et al ., ). Recently, serum miRNA and metabolomics have been found to be diagnostic and prognostic biomarker for non‐small‐cell lung cancer.…”