Abstract
Cytology and histology forms the cornerstone for the diagnosis of non-small cell lung cancer (NSCLC) but obtaining sufficient tumour cells or tissue biopsies for these tests remains a challenge. We investigate the lipidome of lung pleural effusion (PE) for unique metabolic signatures to discriminate benign versus malignant PE and EGFR versus non-EGFR malignant subgroups to identify novel diagnostic markers that is independent of tumour cell availability. Using liquid chromatography mass spectrometry, we profiled the lipidomes of the PE of 30 benign and 41 malignant cases with or without EGFR mutation. Unsupervised principal component analysis revealed distinctive differences between the lipidomes of benign and malignant PE as well as between EGFR mutants and non-EGFR mutants. Docosapentaenoic acid and Docosahexaenoic acid gave superior sensitivity and specificity for detecting NSCLC when used singly. Additionally, several 20- and 22- carbon polyunsaturated fatty acids and phospholipid species were significantly elevated in the EGFR mutants compared to non-EGFR mutants. A 7-lipid panel showed great promise in the stratification of EGFR from non-EGFR malignant PE. Our data revealed novel lipid candidate markers in the non-cellular fraction of PE that holds potential to aid the diagnosis of benign, EGFR mutation positive and negative NSCLC.
Highlights
Adequate tumour cell and tissue acquisition is paramount for diagnosis, histologic and molecular characterization of NSCLC
As observed in a recent study performed by Liu and co-workers, the malignant pleural effusion (PE) supernatant was reported to have a low sensitivity of 63.6% in comparison to the tumour tissue[14]
The motivation for this study stemmed from challenges in the diagnosis of NSCLC, which is highly dependent on the availability of tissue biopsy or cells for the standard testing of malignancy and mutation status (e.g. EGFR, ALK mutations)
Summary
Adequate tumour cell and tissue acquisition is paramount for diagnosis, histologic and molecular characterization of NSCLC. It is noteworthy that other studies reported favourable clinical usefulness of cell-free DNA from blood for the detection of EGFR mutations as supported by promising diagnostic performance (sensitivity up to ~80% and specificity of 100%)[15,16] These studies demonstrated some of the efforts to identify surrogate markers in liquid biopsy that are indicative of the mutation subtype so as to overcome the issue of limited availability of tumour tissue for genotyping. The identification of fatty acid marker metabolites in the study by Lam et al coincide with the lipid reprogramming phenomenon in cancer biology that is gaining increasing recognition in recent years[20,21] This underscored the value in scrutinizing the lipidome of PE in NSCLC diagnosis. Our secondary objective aims to identify lipid species with the ability to distinguish malignant PE from NSCLC patients with and without EGFR mutations
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