Abstract
Lung cancer is the leading cause of cancer-related death in the United States. Here, we evaluated the potential clinical utility of soluble human epidermal growth factor receptor 2 (sHER2) for the risk assessment, screening, and diagnosis of non-small cell lung cancer (NSCLC) using an unmatched case-control study design. Serum sHER2 concentrations were measured by immunoassay in 244 primary NSCLC cases and 218 healthy controls. Wilcoxon rank-sum tests, logistic regression models, and receiver operating characteristic plots were used to assess whether sHER2 is associated with lung cancer. Median serum sHER2 concentrations are higher in patients with adenocarcinoma than squamous cell carcinoma regardless of gender, and sHER2 is a weak, independent biomarker of adenocarcinoma, but not of squamous cell carcinoma, adjusted for age and gender. The age-adjusted relative risk (odds) of adenocarcinoma is 3.95 (95% CI: 1.22, 12.81) and 7.93 (95% CI: 2.26, 27.82) greater for women and men with high sHER2 concentrations (≥6.60 ng/mL) vs. low sHER2 concentrations (≤1.85 ng/mL), respectively. When adjusted for each other, sHER2, age, and gender discern healthy controls from patients with primary adenocarcinomas of the lung with 85.9% accuracy. We conclude that even though serum sHER2 is not a strong, stand-alone discriminatory biomarker of adenocarcinoma, sHER2 may be a useful, independent covariate in multivariate risk assessment, screening, and diagnostic models of lung cancer.
Highlights
Lung cancer is the leading cause of cancer-specific mortality for men and women in the U.S [1,2,3].The National Cancer Institute’s (NCI) Surveillance Epidemiology and End Results program estimated that 226,160 new lung cancer cases were diagnosed in the U.S in 2012, and that 160,340 individuals died of this disease
We evaluated 244 primary non-small cell lung cancer (NSCLC) cases and 218 healthy controls using an unmatched, retrospective, case-control study design to determine whether age and/or gender are confounders or effect modifiers of the relationship between soluble human epidermal growth factor receptor 2 (sHER2) and NSCLC
Our observations that sHER2 concentrations decrease with age in healthy men, and that age and gender confound the relationship between sHER2 concentrations and lung adenocarcinoma are consistent with hormonal regulation of HER2 expression and/or shedding
Summary
Lung cancer is the leading cause of cancer-specific mortality for men and women in the U.S [1,2,3].The National Cancer Institute’s (NCI) Surveillance Epidemiology and End Results program estimated that 226,160 new lung cancer cases were diagnosed in the U.S in 2012, and that 160,340 individuals died of this disease. 99% consist of either small cell carcinomas (13.9%) or non-small cell carcinomas (85.1%). Histological subtypes of non-small cell lung cancer (NSCLC). Early stage lung cancer have a 5-year survival rate of 49.5% and may be cured by surgical resection [4,5]. 77% of lung cancer patients have advanced stage disease at diagnosis, and their 5-year survival rate is only 20.6% for disease that has spread to the regional lymph nodes or 2.8% for disease that has metastasized to distant anatomical sites. Because patients who are diagnosed with early stage lung cancer have a significantly better prognosis, screening (i.e., early detection) represents a practical public health approach for decreasing lung cancer mortality
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