Dataset Information

Proteomic Analysis Enables Distinction of Early- Versus Advanced-Stage Lung Adenocarcinomas

ABSTRACT: Background: A gel-free proteomic approach was utilized to perform in-depth tissue protein profiling of lung adenocarcinoma (ADC) and normal lung tissues from early and advanced stages of the disease. The long-term goal of this study is to generate a large-scale, label-free proteomic data set from histologically well-classified lung ADC that can be used to increase further our understanding of disease progression and aid in identifying novel biomarkers. Methods and Results: Cases of early-stage (I-II) and advanced-stage (III-IV) lung ADCs were selected and paired with normal lung tissues from 22 patients. The histologically and clinically stratified human primary lung adenocarcinomas were analyzed by liquid chromatography tandem mass spectrometry (LC-MS/MS). From the analysis of ADC and normal specimens, 5,933 protein groups were identified. To examine the protein expression profile of ADC, a peak area-based quantitation method was used. In early- and advanced-stage ADC, 33 and 39 proteins were differentially-expressed respectively between normal and tumor tissue (adjusted p-value < 0.01, fold change ≥ 4). For early- and advanced stage ADC tumors compared to normal patient-matched tissue, 11 and 22 proteins and 23 and 16 proteins were identified as down- and up-regulated, respectively. In silico functional analysis of the up-regulated proteins in both tumor groups revealed that most of the enriched pathways are involved in mRNA metabolism. Furthermore, the most over-represented pathways in the proteins that were unique to ADC are related to mRNA metabolic processes. Conclusions: Further analysis of these data may provide an insight into the molecular pathways involved in disease etiology and may lead to the identification of biomarker candidates and potential targets for therapy. Our study provides potential diagnostic biomarkers for lung ADC and novel stage-specific drug targets for rational intervention.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Lung

DISEASE(S): Lung Adenocarcinoma

SUBMITTER: Indira Pla Parada

LAB HEAD: Gyorgy Marco-Varga

PROVIDER: PXD019259 | Pride | 2021-09-09

REPOSITORIES: Pride

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Proteomic analysis enables distinction of early- versus advanced-stage lung adenocarcinomas.

Kelemen Olga O Pla Indira I Sanchez Aniel A Rezeli Melinda M Szasz Attila Marcell AM Malm Johan J Laszlo Viktoria V Kwon Ho Jeong HJ Dome Balazs B Marko-Varga Gyorgy G

Clinical and translational medicine 20200614 2

<h4>Background</h4>A gel-free proteomic approach was utilized to perform in-depth tissue protein profiling of lung adenocarcinoma (ADC) and normal lung tissues from early and advanced stages of the disease. The long-term goal of this study is to generate a large-scale, label-free proteomics dataset from histologically well-classified lung ADC that can be used to increase further our understanding of disease progression and aid in identifying novel biomarkers.<h4>Methods and results</h4>Cases of ...[more]

PMID: 32536039

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Project description:Bronchioloalveolar carcinoma (BAC), a subtype of lung adenocarcinoma (ADC) without stromal, vascular, or pleural invasion, is considered an in situ tumor with a 100% survival rate. However, the histological criteria for invasion remain controversial. BAC-like areas may accompany otherwise invasive adenocarcinoma, referred to as mixed type adenocarcinoma with BAC features (AWBF). AWBF are considered to evolve from BAC, representing a paradigm for malignant progression in ADC. However, the supporting molecular evidence remains forthcoming. Here, we have studied the genomic changes of BAC and AWBF by array comparative genomic hybridization (CGH). We used submegabase-resolution tiling set array CGH to compare the genomic profiles of 14 BAC or BAC with focal area suspicious for invasion with those of 15 AWBF. Threshold-filtering and frequency-scoring analysis found that genomic profiles of noninvasive and focally invasive BAC are indistinguishable and show fewer aberrations than tumor cells in BAC-like areas of AWBF. These aberrations occurred mainly at the subtelomeric chromosomal regions. Increased genomic alterations were noted between BAC-like and invasive areas of AWBF. We identified 113 genes that best differentiated BAC from AWBF and were considered candidate marker genes for tumor invasion and progression. Correlative gene expression analyses demonstrated a high percentage of them to be poor prognosis markers in early stage ADC. Quantitative PCR also validated the amplification and overexpression of PDCD6 and TERT on chromosome 5p and the prognostic significance of PDCD6 in early stage ADC patients. We identified candidate genes that may be responsible for and are potential markers for malignant progression in AWBF. Keywords: array comparitive genomic hybridization, bronchioloalveolar carcinoma, non-small-cell lung carcinoma, prognostic markers Array comparitive genomic hybridization analysis of 29 Lung Adenocarcinomas with Bronchioalveolar Features.

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