Abstract PR04: Distinctive squamous cell carcinoma protein signatures.
Authors: Ostroff Rachel , Mehan Michael R. , Williams Stephen , Brody Edward , Pass Harvey , Rom William , Siegfried Jill , Muley Thomas , Franklin Wilbur , Merrick Dan , Bokhoven Adrie van , Wolf Holly , Feser William , Barón Anna E. , Miller York 
Published: August 2014

Abstract
Squamous cell carcinoma (SQ) of the lung causes approximately 400,000 deaths per year worldwide, and no specifically targeted treatments yet exist. We used the SOMAscan proteomic platform (which measures 1129 proteins with a median limit of detection of 40 fM and 5% CV) in a broad-based analysis of serum and tissue samples to gain insight into the distinctive drivers of SQ malignant growth. We discovered unique SQ markers and pathways that show early expression of invasion and metastasis signals. Strong SQ signals were revealed. Our multi-center serum study of 94 non-small cell lung cancer (NSCLC) cases and 269 long-term smoker and benign pulmonary nodule controls resulted in the discovery of 60 lung cancer biomarkers and the development of a 7-marker diagnostic panel. This panel was validated in two independent cohorts. The AUC for detection of SQ carcinoma was 0.93 in training and 0.89 in the Univ. of Heidelberg validation set (56 SQ cases/27 benign nodule controls). Performance was confirmed with an AUC of 0.87 in an independent validation cohort assembled by the EDRN (25 SQ cases/20 benign nodules/52 smoker controls). This non-invasive test could be used as an adjunct to CT to detect rapidly growing SQ tumors that are disproportionately missed as interval cancers in CT screening studies. In addition, we analyzed 68 NSCLC tumor and matched non-tumor tissue lysates. This study consisted of 49 adenocarcinoma (AD) and 19 SQ tumors, 88% of which were Stage I or II. Proteomic comparisons of tumor/non-tumor or AD/SQ tissue samples performed using the Mann-Whitney test identified 79 tumor markers. Differences between tumor and non-tumor tissue were dominated by inflammatory, apoptotic and cell proliferation proteins. Just as we observed in the serum studies, the most common pattern was an increasing difference in protein levels from non tumor to AD to SQ. Of note, 24% of the proteins were only markers in SQ. These SQ-only markers are enriched for angiogenesis, cell proliferation and cell adhesion functions. Unexpected findings that the SQ proteome is dominated by proteins that promote malignancy and metastasis even in early stage tumors were revealed through broad proteomic profiling. These insights may lead to essential connections between the biochemical pathways altered in malignancy and tools for SQ cancer diagnosis and treatment.
This abstract is also presented as Poster B14.
Citation Format: Rachel Ostroff, Michael R. Mehan, Stephen Williams, Edward Brody, Harvey Pass, William Rom, Jill Siegfried, Thomas Muley, Wilbur Franklin, Dan Merrick, Adrie van Bokhoven, Holly Wolf, William Feser, Anna E. Barón, York Miller. Distinctive squamous cell carcinoma protein signatures. [abstract]. In: Proceedings of the AACR-IASLC Joint Conference on Molecular Origins of Lung Cancer; 2014 Jan 6-9; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2014;20(2Suppl):Abstract nr PR04.