The relationship between serum levels of GRP78, GRP94, calnexin, and calreticulin and prognosis in patients with lung cancer.

Abstract

BackgroundTo determine the serum levels of endoplasmic reticulum (ER) chaperones, glucose-regulated protein 78 (GRP78), glucose-regulated protein 94 (GRP94), calnexin, and calreticulin in patients with lung cancer and in the control group and to evaluate the relationship between chaperone levels and clinical data and patient survival.MethodsGRP78, GRP94, calnexin and calreticulin were measured in serum by ELISA. The serum chaperone levels of patients with lung cancer and the control group were compared. The relationship between serum chaperone levels and clinical data and patient prognosis was evaluated. The median survival time was calculated using the Kaplan-Meier method. Cox regression analysis was performed to determine the hazard ratio of ER chaperones considering prognostic factors.ResultsThe serum levels of all ER chaperones GRP78, GRP94, calnexin, and calreticulin were higher in patients with lung cancer than in the control group and correlated with each other. Serum calreticulin levels were not affected by demographic and clinical characteristics. Serum levels of GRP78, GRP94, and calnexin were not associated with survival. However, median survival ± SE (95%CI) was 16.00 ± 1.72 (12.62-19.38) months in patients with serum calreticulin levels of 250.52 ng/ml and above, while it was 8.00 ± 1.38 (5.29-10.71) months in patients with calreticulin levels below the cut-off value (log-rank = 6.919; p = 0.009). Calreticulin impacted survival, even after adjustment for sex, histologic subtype, stage, treatment, and response to chemotherapy, which impacted survival [HR (95%CI): 0.656 (0.433-0.995); p = 0.047].ConclusionCalreticulin is promising for delineating risk groups in lung cancer screening studies, guiding treatment and monitoring outcomes.