Abstract
The accurate diagnosis of small cell lung cancer (SCLC) at initial presentation is essential to ensure appropriate treatment. No validated blood biomarkers that could distinguish SCLC from non-small cell lung cancer (NSCLC) has yet been developed. Dried blood spot (DBS) microsampling has gained increasing interest in biomarkers discovery. In this study, we first performed metabolomic profiling of DBS samples from 37 SCLC, 40 NSCLC, and 37 controls. Two gender-specific multianalyte discriminant models were established for males and females, respectively to distinguish SCLC from NSCLC and controls. The receiver operator characteristic (ROC) curve analysis showed the diagnostic accuracy of 95% (95% CI: 83%-100%) in males SCLC using five metabolites in DBS and 94% (95% CI: 74%-100%) for females using another set of five metabolites. The robustness of the models was confirmed by the random permutation tests (P < 0.01 for both). The performance of the discriminant models was further evaluated using a validation cohort with 78 subjects. The developed discriminant models yielded an accuracy of 91% and 81% for males and females, respectively, in the validation cohort. Our results highlighted the potential clinical utility of the metabolomic profiling of DBS as a convenient and effective approach for the diagnosis of SCLC.
Highlights
Lung cancer is the most common malignant tumor that threatens human health and one of the leading causes of cancer-related death in both men and women [1]
In our previous study, using next-generation metabolomics, we revealed the unique metabolic features in small cell lung cancer (SCLC) cells compared to normal human bronchial epithelial cells (HBECs) and non-small cell lung cancer (NSCLC) cells [12]
We found a significant increase of PI lipids and 2-hydroxy ceramides in the Dried blood spot (DBS) of male SCLC patients compared to NSCLC and the noncancer controls
Summary
Lung cancer is the most common malignant tumor that threatens human health and one of the leading causes of cancer-related death in both men and women [1]. SCLC accounts for about 10–15% of all lung cancer diagnosis. The two subtypes of lung cancer behave differently and are treated very differently [2]. It is essential for the accurate classification of the subtypes of lung cancer at initial presentation to ensure the selection of appropriate treatment approaches. The diagnosis of SCLC primarily relies on the histological and cytological results from tumor tissue biopsies. Immunohistochemistry (IHC) might be helpful to increase the confidence of the pathologists in SCLC classification. SCLC often originates in the submucosal tissue, which makes the accurate collection of tumor samples challenging [5]. The analysis of tumor markers in biological fluids such as the serum, plasma, and urine has remarkable advantages over histologic differentiation
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