Abstract
Lung cancer is the deadliest cancer worldwide, mainly due to its advanced stage at the time of diagnosis. A non-invasive method for its early detection remains mandatory to improve patients’ survival. Plasma levels of 351 proteins were quantified by Liquid Chromatography-Parallel Reaction Monitoring (LC-PRM)-based mass spectrometry in 128 lung cancer patients and 93 healthy donors. Bootstrap sampling and least absolute shrinkage and selection operator (LASSO) penalization were used to find the best protein combination for outcome prediction. The PanelomiX platform was used to select the optimal biomarker thresholds. The panel was validated in 48 patients and 49 healthy volunteers. A 6-protein panel clearly distinguished lung cancer from healthy individuals. The panel displayed excellent performance: area under the receiver operating characteristic curve (AUC) = 0.999, positive predictive value (PPV) = 0.992, negative predictive value (NPV) = 0.989, specificity = 0.989 and sensitivity = 0.992. The panel detected lung cancer independently of the disease stage. The 6-protein panel and other sub-combinations displayed excellent results in the validation dataset. In conclusion, we identified a blood-based 6-protein panel as a diagnostic tool in lung cancer. Used as a routine test for high- and average-risk individuals, it may complement currently adopted techniques in lung cancer screening.
Highlights
Identifying solid cancers by a simple blood analysis has been a long-standing goal in cancer research as the detection of cancer during the regular screening can offer the patients immediate treatment solutions
Previous multi-omics discovery efforts performed in our laboratories suggested 559 proteins to be associated with lung cancer and potentially detectable in human blood [10,11,17,18]
The plasma levels of the 323 proteins were quantified by Liquid Chromatography-Parallel Reaction Monitoring (LC-PRM) in plasma from lung cancer patients and healthy donors
Summary
Identifying solid cancers by a simple blood analysis has been a long-standing goal in cancer research as the detection of cancer during the regular screening can offer the patients immediate treatment solutions. While blood-based early diagnostics for cancer still remains a challenge, several proteins circulating in the blood have been useful for monitoring treatment response and/or tumor recurrence [1]. Only prostate-specific antigen is routinely measured in blood for early diagnosis of cancer [2]. Cohen and colleagues published the results of CancerSeek, a blood test that assesses the presence of 8 protein markers and 1933 genetic alterations in cell-free DNA to diagnose common solid tumors [3]. The median sensitivity of CancerSeek in lung cancer was ~59%, the second lowest among the 8 cancer types investigated [3]
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