Circulating Heat Shock Protein 70 Is a Novel Biomarker for Early Diagnosis of Lung Cancer

Abstract

Heat shock protein 70 (HSP70) was a highly conserved protein which was significantly induced in response to cellular stresses. HSP70 played an important role in the pathogenesis of cancer which stabilized the production of large amount of oncogenic proteins and finally supported growth and survival of tumor. However, there was no report about the diagnosis of circulating HSP70 in lung cancer patients. In this study, a total of 297 participants (lung cancer: 197, healthy control: 100) were enrolled in the detection of circulating HSP70 level in plasma by ELISA assay. The results indicated that circulating HSP70 significantly decreased in lung cancer patients compared to healthy controls (P<0.0001). Receiver operating characteristic (ROC) analysis showed that HSP70 (AUC: 82.2%, SN: 74.1%, SP: 80.0%) had higher diagnosis value than clinical existing biomarkers CEA (AUC: 80.1%, SN: 76.8%, SP: 67.3%) and CA 19-9 (AUC: 63.7%, SN: 64.2%, SP: 54.0%). In the analysis of early lung cancer patients, ROC results also revealed that HSP70 (AUC: 83.8%, SN: 71.2%, SP: 84.0%) have higher sensitivity, specificity, and AUC than CEA (AUC: 73.7%, SN: 73.2%, SP: 69.1%) and CA 19-9 (AUC: 61.5%, SN: 69.4%, SP: 53.4%). In analysis of specific histological classifications, HSP70 showed more valuable in the diagnosis of SCC (AUC: 85.9%, SN: 86.1.9%, SP: 81.0%) than ADC (AUC: 81.0%, SN: 69.1%, SP: 81.0%). Combined analysis of HSP70 and existing biomarker: CEA and CA 19-9 exhibited that HSP70 combined CEA and CA 19-9 showed the highest AUC (0.945, 95% CI, 0.855-1.000). The importance of our results was that we found decreased circulating HSP70, in combination with elevated CEA and CA 19-9, could be utilized in the diagnosis of early (stage I and II) lung cancer.