Value of serum tumor markers for predicting EGFR mutations and positive ALK expression in 1089 Chinese non-small-cell lung cancer patients: A retrospective analysis

• Published in: European journal of cancer (1990) Vol. 124; pp. 1 - 14
• Main Authors: Wang, Sufei, Ma, Pei, Ma, Guanzhou, Lv, Zhilei, Wu, Feng, Guo, Mengfei, Li, Yumei, Tan, Qi, Song, Siwei, Zhou, E., Geng, Wei, Duan, Yanran, Li, Yan, Jin, Yang
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01-01-2020; Elsevier Science Ltd
• Subjects: Adenocarcinoma; Age; Anaplastic lymphoma kinase; Antigens; Biomarkers; Carbohydrates; Carcinoembryonic antigen; Confidence intervals; Cytokeratin; Design of experiments; Epidermal growth factor; Epidermal growth factor receptor; Epidermal growth factor receptors; Experimental design; Females; Ferritin; Growth factors; Kinases; Lung cancer; Lymphoma; Markers; Multivariate analysis; Mutants; Mutation; Non-small cell lung carcinoma; Non-small-cell lung cancer; Patients; Protein-tyrosine kinase; Regression analysis; Serum tumor markers; Small cell lung carcinoma; Smoking; Squamous cell carcinoma; Statistical analysis; Subgroups; Tumor markers; Tumors; Non-small-cell lung cancer; Serum tumor markers; Anaplastic lymphoma kinase; Epidermal growth factor receptor
• ISSN: 0959-8049; 1879-0852
• DOI: 10.1016/j.ejca.2019.10.005

The role of serum tumor markers (STMs) in the modern management of epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) mutations in lung cancer remains poorly described. In this study, we investigated whether STMs could be a valuable noninvasive tool to predict EGFR mutations and ALK positivity in non-small-cell lung cancer (NSCLC) patients.
We retrospectively reviewed and included 1089 NSCLC patients who underwent EGFR or ALK mutation testing and STMs measurement prior to treatment. The differences in several clinical characteristics and STMs between the subgroups were analyzed. Multivariate logistic regression analysis was performed to identify predictors of EGFR mutations and ALK positivity.
EGFR mutations were found more frequently in females (63.11%), never-smokers (59.69%), and those with lung adenocarcinoma (ADC) (53.87%). Negative carbohydrate antigen (CA) 125, ferritin (FERR), squamous cell carcinoma antigen (SCC), and soluble fragment of cytokeratin 19 (CYFRA 21-1) levels were significantly associated with EGFR mutations (p < 0.05). Multivariate analysis demonstrated that ADC, never-smoker status, and negative CA 125 and SCC results were predictors of EGFR mutations (p < 0.05). The receiver operating characteristic (ROC) curve yielded an area under the curve (AUC) of 0.715 (95% confidence interval [CI]: 0.673–0.758) for the combination of the four factors. Positive ALK expression was found more frequently in younger patients (median age: 49 years), females (8.40%), never-smokers (8.82%), and those negative for carcinoembryonic antigen (CEA) (8.02%). Multivariate analysis demonstrated that younger age and never-smoker status were the only independent predictors of ALK positivity (p < 0.05). The ROC curve yielded an AUC of 0.760 (95% CI: 0.677–0.844) for the combination of these two factors.
STMs are associated with mutant EGFR status and could be integrated with other clinical factors to enhance the ability to distinguish EGFR mutation status among NSCLC patients. For ALK-positive patients, younger age and never-smoker status could predict the mutation status, whereas STMs could not.
•ADC, never-smoker status, and negative CA 125 SCC levels can predict EGFR mutation status in NSCLC patients (AUC, 0.715).•Younger age and never-smoker status are independent predictors of ALK positivity (AUC, 0.760).