Abstract
Polycomb group member protein BMI1 is involved in maintaining cell identity, proliferation, differentiation and human oncogenesis. In the present study, we determined BMI1 mRNA expression in whole blood and evaluated the impact of the expression level on the treatment response and survival of 96 advanced NSCLC patients treated with first-line platinum-based chemotherapy. We also determined BMI1 mRNA expression in primary tumors from 22 operable NSCLC patients treated with radical surgery. We found that compared with control subjects, BMI1 mRNA expression in whole blood of advanced NSCLC patients was decreased (P<0.001). Similarly, we observed decreased BMI1 mRNA expression in primary tumors compared to normal lungs from operable NSCLC patients (P=0.001). We found high BMI1 mRNA expression in blood was associated with longer progression-free survival (PFS) (P=0.049) and overall survival (OS) (P=0.012) in advanced NSCLC patients treated with first-line platinum-based chemotherapy. However, no association between the BMI1 mRNA level and response to chemotherapy was found (P=0.21). Multivariate Cox proportional hazards regression analysis showed elevated BMI1 mRNA level in whole blood was an independent prognostic factor for longer PFS (P=0.012) and OS (P<0.001). In conclusion, BMI1 mRNA expression in whole blood might represent a new biomarker for the diagnosis and prognosis of NSCLC.
Highlights
Lung cancer is the most frequently diagnosed cancer and the main cause of cancer-related mortality worldwide
These proteins have an essential role in maintaining cell identity, growth and differentiation [18], which is reflected by the fact that an abnormal B-lymphoma Moloney murine leukemia virus insertion region-1 (BMI1) expression pattern is linked to oncogenesis
Our results showed that BMI1 expression in whole blood of advanced Non-small cell lung cancer (NSCLC) patients was decreased compared with the control group of patients
Summary
Lung cancer is the most frequently diagnosed cancer and the main cause of cancer-related mortality worldwide. The disease accounts for more than 1.8 million newly diagnosed cancer cases globally (13 % of the total) and is estimated to be responsible for nearly 1.6 million deaths (19 % of the total) [1, 2]. Lung cancer prognosis remains poor, with an overall 5-year survival in Europe of only 13 % [3]. Non-small cell lung cancer (NSCLC) accounts for approximately 85 % of all lung cancer cases [4]. Due to the aggressive nature of the disease and the lack of effective screening methods, most NSCLC patients are diagnosed with advanced, incurable disease, and the prognosis of patients with advanced NSCLC without recognizable oncogene drivers remains poor, with a median overall survival of only 10-14 months for patients treated with standard platinum-based chemotherapy [6]
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