Unknown,Transcriptomics,Genomics,Proteomics

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Tumor-microenvironment interactions studied by zonal transcriptional profiling of squamous cell lung carcinoma

ABSTRACT: To better understand the interaction between tumor cells and their microenvironment with regard to mechanisms of invasion, total RNA was isolated from the inner-tumor, tumor invasion front, adjacent lung and distant normal lung tissue from 18 patients with squamous cell lung carcinoma using punch-aided laser capture microdissection. Comprehensive mRNA expression profiles were obtained from microarray expreiments and statistical analyses revealed extensive changes in gene expression when comparing the inner tumor and tumor front with the normal lung and lung front. However, only a few genes were differentially expressed between the tumor front and the inner tumor. The identified genes indicate prostaglandin mediated inflammatory processes at the invasion front Sample for microarray experiments were taken from the inner-tumor, tumor invasion front, adjacent lung and distant normal lung tissue from 18 patients with squamous cell lung carcinoma using punch-aided laser capture microdissection. Sample RNA and Universal Reference RNA (Stratagene, La Jolla, USA) were amplified and separately labeled with both Cy3 and Cy5. All samples were subjected to two-color hybridizations (sample against reference) with color-switch experiments yielding two technical replicates, respectively.

ORGANISM(S): Homo sapiens

SUBMITTER: Daniel Haag

PROVIDER: E-GEOD-31446 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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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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Tumor-microenvironment interactions studied by zonal transcriptional profiling of squamous cell lung carcinoma

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