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BackgroundThe thioredxin reductases 1 (TrxR1) is one of the major antioxidant and redox regulators in mammalian cells. Studies have shown that TrxR1 is over expressed in many malignancy diseases. However, few studies have evaluated the role of TrxR1 in non-small cell lung cancer (NSCLC).MethodsSerum levels of TrxR1 and CEA in 142 patients with EGFR wild type and ALK negative advanced NSCLC was measured by ELISA assay before first line standard doublet chemotherapy from June 2013 to February 2016 in Hunan Cancer Hospital. Clinical characteristics and Survival data were collected and analyzed according to serum TrxR1 levels.ResultsNo significant differences were founded from clinic pathological variables. With the cut-off value of 12U/mL, the lower serum TrxR1 activity patients had long progression-free survival (PFS) and overall survival (OS) compared with higher patients (PFS: 5.3m vs. 3.6m p=0.044, OS: 14.5m vs. 11m p<0.001). In subgroup, lower serum TrxR1 activity patients had long OS both in adenocarcinoma (ADC) (17m vs. 8m, p=0.003) and squamous cell carcinoma (SCC) (13m vs. 11m, p=0.035). While combining with TrxR1 activity and serum CEA concentrations, we founded that patients with lower serum TrxR1 activity and serum CEA concentrations had long OS compared with higher group patients (20m vs. 7m, p<0.001).ConclusionsSerum TrxR1 activity was not affected by clinic pathological variables. Measurement of serum TrxR1 activity might be an independent prognostic factor for EGFR wild type and ALK negative advanced NSCLC patients. Combination of serum TrxR1 activity and serum CEA concentrations need to be further profiled from bench to beside.

The use of immune checkpoint inhibitors targeting PD‐1 and PD‐L1 in advanced non‐small cell lung cancer (NSCLC) has been one of the most significant improvements in recent years. However the resistance mechanisms of immune checkpoint inhibitors require further investigation. Herein we attempted to determine the possible resistance mechanism of nivolumab in a male smoker with advanced adenosquamous carcinoma. After experiencing disease progression on systematic chemotherapy, he was administered nivolumab as a result of high PD‐L1 expression. Larger panel gene detection was performed after the failure of nivolumab treatment to investigate the possible resistance mechanism and a new EGFR exon 21 L858R mutation was detected. After a achieving a response with gefitinib, the patient suffered a rapid relapse and died of tumor progression. This case represents the first time EGFR exon 21 L858R has been detected as an acquired resistance mutation to nivolumab. Patients with high PD‐L1 expression may exhibit a poor response to EGFR‐tyrosine kinase inhibitors. Large panel gene detection remains the optimal choice when confronted with drug resistance.