Abstract
BackgroundCell surface proteins have provided useful targets and biomarkers for advanced cancer therapies. The recent clinical success of antibody-drug conjugates (ADCs) highlights the importance of finding selective surface antigens for given cancer subtypes. We thus attempted to develop stand-alone software for the analysis of the cell surface transcriptome of patient cancer samples and to prioritize lineage- and/or mutation-specific over-expression markers in cancer cells.ResultsA total of 519 genes were selected as surface proteins, and their expression was profiled in 14 cancer subtypes using patient sample transcriptome data. Lineage/mutation-oriented analysis was used to identify subtype-specific surface markers with statistical confidence. Experimental validation confirmed the unique over-expression of predicted surface markers (MUC4, MSLN, and SLC7A11) in lung cancer cells at the protein level. The differential cell surface gene expression of cell lines may differ from that of tissue samples due to the absence of the tumor microenvironment.ConclusionsIn the present study, advanced 3D models of lung cell lines successfully reproduced the predicted patterns, demonstrating the physiological relevance of cell line-based 3D models in validating surface markers from patient tumor data. Also QSurface software is freely available at http://compbio.sookmyung.ac.kr/~qsurface.
Highlights
Cell surface proteins have provided useful targets and biomarkers for advanced cancer therapies
We developed stand-alone software, QSurface, to analyze lineage- and/or mutation-specific cell surface transcriptome marker from cancer patients’ samples obtained from The Cancer Genome Atlas (TCGA)
Data acquisition RNA sequencing version 2 (RNASeqV2) data from patients’ tumor and normal tissue samples were downloaded from TCGA website in 2015
Summary
Cell surface proteins have provided useful targets and biomarkers for advanced cancer therapies. We attempted to develop stand-alone software for the analysis of the cell surface transcriptome of patient cancer samples and to prioritize lineage- and/or mutation-specific over-expression markers in cancer cells. Cell surface proteins have provided major targets and biomarkers for anticancer therapies. The expression of surface proteins such as CDH17, CD138 and members of the integrin family is related with tumor progression [1]. Another surface protein, SEZ6L2 was identified a novel prognostic marker in non-small cell lung cancer (NSCLC) [2]. Many drugs targeting EGFR have been developed [3].
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