Adenocarcinoma (AC) and
squamous cell carcinoma (SCC), sub-types of
non-small cell lung cancer (NSCLC), both present unique features at the genome, epigenome, transcriptome and
proteome levels, as well as shared clinical and histopathological characteristics, but differ in terms of treatment. To ensure proper treatment, one must be able to distinguish between these sub-types. Here, we identify novel
biomarker proteins in NSCLC, allowing for distinguishing between the AC and SCC sub-types. Proteomics analysis distinguished between healthy and
tumor tissues, with the expression level of 1,494
proteins being altered, 378 of which showed a ≥|100|-fold change. Enrichment of
proteins related to
protein synthesis and degradation, and of
proteins associated with mitochondria, metabolism, and apoptosis, was found. Network analysis defined groups of
proteins, such as those associated with cell metabolic processes or with
fatty acid/lipid metabolism and transport. Several
biomarkers that enable for distinguishing between AC and SCC were identified here for the first time, and together with previous reports confirmed here, led us to propose a list of
proteins differentially expressed in SCC and AC. Some of these
biomarkers are clear signatures for AC or SCC and four of them are secreted
proteins. The presence of the
mitochondrial protein SMAC/Diablo in the nucleus was found to be a signature for SCC. Precise diagnosis of AC and SCC is essential for selecting appropriate treatment and thus, increasing patient life expectancy. Finally, the search for drugs that target some of these
biomarkers may lead to new treatments for
lung cancer.