An importance of clinical proteomics for personalized medicine of lung cancer subtypes

Mass spectrometry-based clinical proteomic analysis, combined with collection of taegeted cancerous cells laser-microdissected (LMD) from formalin-fixed paraffinembedded (FFPE) tissues, has been promising to unveil both proteins expressed and their functional networks in lung cancer subtypes. Among lung cancer subtypes, both large cell neuroendocrine carcinoma (LCNEC) of the lung and small cell lung carcinoma (SCLC) are now classified to neuroendocrine tumor (NET) but pre-therapeutic histological distinction between LCNEC and SCLC has so far been problematic, leading to adverse clinical outcome. Protein biomarker candidates for LCNEC were found to be interestingly known as cancer stem cell (CSC) markers including aldehyde dehydrogenase 1 family member A1 (ALDH1A1), and those for SCLC included novel NET marker candidates, brain acid soluble protein 1 (BASP1) and secretagogin (SEGN), and a known NET marker, neural cell adhesion molecule (CD56). For three types of lung adenocarcinomas (ACs), which are adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA), and lepidic predominant invasive asenocarcinoma (LEP), their preliminary clinical proteomic analyses revealed protein expression profiles characterizing those lung cancer subtypes. The STRING protein-protein interaction (PPI) network analysis followed by gene set enrichment (GSE) for proteins expressed significantly to the three lung AC subtypes manifested characteristic associations of cancer-related pathways, which might play consertedly important roles in progression of disease mechanisms, and which would be quite useful to understand carcinogenic processes of lung adenocarcinom. Thus outcomes from clinical proteomic analysis reveal not only biomarker protein candidates expressed significantly to a disease but also serve to elucidate disease-oriented protein-protein interaction (PPI) networks including functional networks predicted from experimentally obtained proteome datasets. Abbreviations: LCNEC: Large-Cell Neuroendocrine Lung Carcinoma, OLC: Other Large-Cell Lung Cancer, SCLC: Small-Cell Lungcancer, GGO: Focal Ground-Glass Opacity, AIS: Adenocarcinoma In Situ, MIA: Minimally Invasive Adenocarcinoma, LEP: Lepidic Predominant Invasive Adenocarcinoma, FFPE: Formalin-Fixed and Paraffin-Embedded tissue sections, MS: Mass Spectrometry, PPI: Comparative Proteomics, Protein-Protein Interaction