Abstract
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.
Highlights
Non-small cell lung cancer (NSCLC) is the most prevalent form of lung cancer and represents the leading cause of cancer deaths worldwide in both men and women.[1]
We identified several metabolism- and apoptosis-related proteins, as well as other proteins, that could serve as potential lung cancer biomarkers for AC and squamous cell carcinoma (SCC), of which AKR1B10, NPC2, GGH and AZGP1 are secreted proteins
The results show that in AC patients, high levels of VDAC1, SMAC or HYOU1 are associated with low survival rates, while high levels of AKR1B10, apoptosis-inducing factor (AIF) and TSG101 are associated with higher survival rates (Figure 7)
Summary
Non-small cell lung cancer (NSCLC) is the most prevalent form of lung cancer and represents the leading cause of cancer deaths worldwide in both men and women.[1]. Www.impactjournals.com/oncotarget and squamous cell carcinoma (SCC), together accounting for the vast majority of NSCLS cases (representing almost 80% of primary lung cancer cases [4]) and being responsible for 30% of all cancer deaths. AC is the most prevalent sub-type of lung cancer in non-smokers [5], and constitutes approximately 50% of all cases of lung cancer [6]. SCC, which constitutes approximately 30% of NSCLC cases, usually develops in central areas of the bronchi of the lung and is closely connected with smoking [7]. These two NSCLC sub-types have both unique and shared clinical presentations and histopathological characteristics, the treatment strategy may differ significantly. Current histological discrimination is based on tissue availability, where in ~ 15-20% of cases, the tissue is exhausted without having being useful for defining final histology result, while as many as 7.2% of cases are poorly differentiated and present not otherwise specified NSCLC
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