# Blood-based lung cancer biomarkers identified through proteomic discovery in cancer tissues, cell lines and conditioned medium

## TL;DR

Researchers identified blood-based biomarkers for early lung cancer detection by analyzing proteins from cancer tissues, cell lines, and cell culture media.

## Contribution

A novel proteomic approach combining multiple sample types to discover and validate blood-based lung cancer biomarkers.

## Key findings

- 179 candidate biomarkers were identified through proteomic analysis of lung cancer samples.
- An 8-marker model accurately distinguished lung cancer patients from high-risk smokers with an AUC of 0.775.
- Biomarkers showed elevated levels in stage I NSCLC patients compared to healthy smokers.

## Abstract

Support for early detection of lung cancer has emerged from the National Lung Screening Trial (NLST), in which low-dose computed tomography (LDCT) screening reduced lung cancer mortality by 20 % relative to chest x-ray. The US Preventive Services Task Force (USPSTF) recently recommended annual screening for the high-risk population, concluding that the benefits (life years gained) outweighed harms (false positive findings, abortive biopsy/surgery, radiation exposure). In making their recommendation, the USPSTF noted that the moderate net benefit of screening was dependent on the resolution of most false-positive results without invasive procedures. Circulating biomarkers may serve as a valuable adjunctive tool to imaging.

We developed a broad-based proteomics discovery program, integrating liquid chromatography/mass spectrometry (LC/MS) analyses of freshly resected lung tumor specimens (n = 13), lung cancer cell lines (n = 17), and conditioned media collected from tumor cell lines (n = 7). To enrich for biomarkers likely to be found at elevated levels in the peripheral circulation of lung cancer patients, proteins were prioritized based on predicted subcellular localization (secreted, cell-membrane associated) and differential expression in disease samples. 179 candidate biomarkers were identified. Several markers selected for further validation showed elevated levels in serum collected from subjects with stage I NSCLC (n = 94), relative to healthy smoker controls (n = 189). An 8-marker model was developed (TFPI, MDK, OPN, MMP2, TIMP1, CEA, CYFRA 21–1, SCC) which accurately distinguished subjects with lung cancer (n = 50) from high risk smokers (n = 50) in an independent validation study (AUC = 0.775).

Integrating biomarker discovery from multiple sample types (fresh tissue, cell lines and conditioned medium) has resulted in a diverse repertoire of candidate biomarkers. This unique collection of biomarkers may have clinical utility in lung cancer detection and diagnoses.

The online version of this article (doi:10.1186/s12014-015-9090-9) contains supplementary material, which is available to authorized users.