Correlation of serum tumor markers and incidence of driver gene mutations in non-small cell lung cancer

Abstract

Objective To explore the correlation between serum tumor markers and mutations of driver genes in non-small cell lung cancer (NSCLC) patients, so as to provide references for serum tumor markers-guided targeted therapies for NSCLC. Methods A cross-sectional study was performed on 1 008 NSCLC patients admitted in the respiratory, oncology and thoracic surgery departments of our medical center from December 2015 to March 2021. All these patients underwent tissue biopsies and driver gene tests. Their clinical data and results of serum tumor markers and lung cancer-specific gene test were collected. The correlation of mutations of driver genes with clinical characteristics and serum tumor markers were analyzed with correlation analysis and receiver operating characteristic (ROC) curve analysis. Then the patients were grouped according to the elevated levels of these tumor markers and presence of surgical indicators or not. The differences in mutation types and rates in the driver genes were observed among different groups of patients. Results In the 1 008 patients, there were 674 males and 334 females, with an average age of 58.4 years. The total incidence of driver gene mutations was 64.5%. Higher mutation rate of epidermal growth factor receptor (EGFR) was observed in the patients with increased serum carcinoembryonic antigen (CEA) level than those without (49.9% vs 32.6%, P < 0.001) and in the patients with unraised cytokeratin fragment 19 (CYFRA21-1) level than those with unchanged or elevated level (48.5% vs 38.3%, P=0.003). And, the serum CEA level was significantly higher in the EGFR mutant patients than those with EGFR wild-type [12.19 (3.49~79.05) vs 4.93 (2.47~17.29) ng/mL, P < 0.001]. With the increase of serum CEA level, the occurrence of EGFR mutations was gradually increased. Stratified analysis showed that in stage ⅢB to Ⅵ patients, the serum CEA level was obviously higher in patients with EGFR mutation than those with EGFR wild-type. The patients with abnormally elevated serum neuron-specific enolase (NSE) level showed higher mutation rate of kirsten rat sarcoma viral oncogene (KRAS) than those with normal NSE level. Conclusion In NSCLC patients, serum CEA level is correlated with occurrence of EGFR mutations. Especially for those with stage ⅢB to Ⅵ, higher serum CEA level indicates higher mutation rate of EGFR. Lung cancer-specific gene test should be recommended to carry out in advanced lung cancer patients with significantly elevated CEA in order to determine whether there are indications for target therapy.

Keywords

• serum tumor markers
• non-small cell lung cancer
• driver gene mutation