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A molecular signature of lung cancer: potential biomarkers for adenocarcinoma and squamous cell carcinoma.

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.

SUBMITTER: Shoshan-Barmatz V

PROVIDER: S-EPMC5739654 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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A molecular signature of lung cancer: potential biomarkers for adenocarcinoma and squamous cell carcinoma.

Shoshan-Barmatz Varda V Bishitz Yael Y Paul Avijit A Krelin Yakov Y Nakdimon Itay I Peled Nir N Lavon Avia A Rudoy-Zilberman Elina E Refaely Yael Y

Oncotarget 20171106 62

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. Proteo ...[more]

PMID: 29285267

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Project description:OBJECTIVE:To analyze the differentially expressed genes (DEGs) between lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) with bioinformatics analysis and search for potential biomarkers for clinical diagnosis of nonsmall cell lung cancer (NSCLC). METHODS:The gene expression profiling datasets of LUAD and LUSC were acquired. The transcriptome differences between LUAD and LUSC were identified using R language processing and t-test analysis. The differential expressions of the genes were shown by Venn diagram. The DEGs identified by GEO2R were analyzed with DAVID and Ingenuity Pathway Analysis (IPA) to identify the signaling pathways and biomarkers that could be used for differential diagnosis of LUAD and LUSC. The TCGA data and the biomarker expression data from clinical lung cancer samples were used to verify the differential expressions of the Osteoarthritis pathway and LXR/RXR between LUAD and LUSC. We further examined the differential expressions of miR-181 and its two target genes, WNT5A and MBD2, in 23 clinical specimens of lung squamous cell carcinoma and the paired adjacent tissues. RESULTS:GEO data analysis identified 851 DEGs (including 276 up-regulated and 575 down-regulated genes) in LUAD and 885 DEGs (including 406 up-regulated and 479 down-regulated genes) in LUSC. DAVID and IPA analysis revealed that leukocyte migration and inflammatory responses were more abundant in LUAD than in LUSC. Osteoarthritis pathway was inhibited in LUAD and activated in LUSC. IPA analysis showed that transcription factors (GATA4, RELA, YBX1, TP63 and MBD2), cytokines (WNT5A and IL1A) and microRNAs (miR-34a, miR-181b and miR-15a) differed significantly between LUAD and LUSC. miR-34a with IL-1A, miR-15a with YBX1, and miR-181b with WNT5A and MBD2 could serve as the paired microRNA and mRNA targets for differential diagnosis of NSCLC subtypes. Analysis of the clinical samples showed an increased expression of miR-181b-5p and the down-regulation of WNT5A, which could be used as molecular markers for the diagnosis of LUSC. CONCLUSIONS:Through transcriptome analysis, we identified candidate genes, paired microRNAs and pathways for differentiating LUAD and LUSC, and they can provide novel differential diagnosis and therapeutic strategies for LUAD and LUSC.

Dataset Information

A molecular signature of lung cancer: potential biomarkers for adenocarcinoma and squamous cell carcinoma.

Publications

A molecular signature of lung cancer: potential biomarkers for adenocarcinoma and squamous cell carcinoma.

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