Abstract
As lung cancer shows the highest mortality in cancer-related death, serum biomarkers are demanded for lung cancer diagnosis and its treatment. To discover lung cancer protein biomarkers, secreted proteins from primary cultured lung cancer and adjacent normal tissues from patients were subjected to LC/MS–MS proteomic analysis. Quiescin sulfhydryl oxidase (QSOX1) was selected as a biomarker candidate from the enriched proteins in the secretion of lung cancer cells. QSOX1 levels were higher in 82% (51 of 62 tissues) of lung cancer tissues compared to adjacent normal tissues. Importantly, QSOX1 serum levels were significantly higher in cancer patients (p < 0.05, Area Under curve (AUC) = 0.89) when measured by multiple reaction monitoring (MRM). Higher levels of QSOX1 were also uniquely detected in lung cancer tissues, among several other solid cancers, by immunohistochemistry. QSOX1-knock-downed Lewis lung cancer (LLC) cells were less viable from oxidative stress and reduced migration and invasion. In addition, LLC mouse models with QSOX1 knock-down also proved that QSOX1 functions in promoting cancer metastasis. In conclusion, QSOX1 might be a lung cancer tissue-derived biomarker and be involved in the promotion of lung cancers, and thus can be a therapeutic target for lung cancers.
Highlights
Lung cancer has been the leading cause of worldwide cancer-associated mortality
The results indicated that elevated QSOX1 might be a lung cancer selective biomarker and be involved in the metastasis or progression of lung cancers
Cells isolated from the adjacent normal tissues showed typical cobble stone-like morphologies of epithelium and cells from lung cancer tissues were irregular and showed a mesenchymal- or fibroblast-like morphology (Figure 1B)
Summary
Lung cancer has been the leading cause of worldwide cancer-associated mortality. Recent 2018 cancer statistics show that lung cancer, along with pancreatic and stomach cancer, shows only minor increase in the 5-year survival rate among all cancers [1,2]. It is speculated that the low survival rate of lung cancer is largely due to the low diagnostic rate in the early stages. Along with advances in proteomics, protein biomarker discovery and clinical application have been actively studied and are regarded as a clinically valuable study by many groups [3,4]. Several protein biomarkers for lung cancer are being developed, including cytokeratin-19 fragments (CYFRA 21-1) [5,6], carcinoembryonic antigen (CEA) [7], neuron-specific enolase (NSE) [8], and cancer antigen-125 (CA-125) [9]. The challenges in biomarker discovery and the time-consuming process leading up to clinical application hinder the development of biomarkers for clinical uses [10]
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