Dataset Information

Expression and prognostic impact of alpha thalassemia/mental retardation X-linked and death domain-associated protein in human lung cancer.

ABSTRACT: Molecular characterization of lung cancer specimens after radical surgery offers additional prognostic information and may help to guide adjuvant therapeutic procedures. The transcriptional regulators alpha thalassemia/mental retardation X-linked (ATRX) and death domain-associated protein (DAXX) have recently been described in different cancer entities as a useful prognostic biomarker. This study was initiated to explore their protein expression patterns and prognostic value in patients with operable lung cancer disease.The protein abundance (in the following text also named protein expression) of ATRX and DAXX were analyzed by immunohistochemistry in 194 samples of squamous cell lung carcinoma (SQCLC), 111 samples of pulmonary adenocarcinoma (AC) and 40 samples of small cell lung cancer (SCLC). The protein levels of ATRX and DAXX were correlated with clinicopathological characteristics and patient outcome.ATRX showed strong protein expression in 16.2% of AC, 11.9% of SQCLC, and 42.5% of SCLC. DAXX was highly expressed in 54.9% of AC, 76.2% of SQCLC, and 82.5% of SCLC. Immunostaining of both ATRX and DAXX were seen in 14.4% of AC, 11.3% of SQCLC, and 42.5% of SCLC. High protein expression of ATRX was a favorable prognostic marker for patients with AC (hazard ratio 0.38, P?=?.02). Sub-group analyses showed a significant correlation between ATRX and the clinical stage of SQCLC and SCLC. Histological grading and ATRX were also significantly associated in cases of SQCLC.The presence of ATRX and DAXX are correlated with lung cancer histology. Strong ATRX protein expression is associated with a significantly longer overall survival in patients with AC.

SUBMITTER: Buentzel J

PROVIDER: S-EPMC6708616 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Expression and prognostic impact of alpha thalassemia/mental retardation X-linked and death domain-associated protein in human lung cancer.

Buentzel Judith J Yao Sha S Elakad Omar O Lois Anna-Maria AM Brünies Jana J König Julia J Hinterthaner Marc M Danner Bernhard C BC Ströbel Philipp P Emmert Alexander A Bohnenberger Hanibal H

Medicine 20190801 31

Molecular characterization of lung cancer specimens after radical surgery offers additional prognostic information and may help to guide adjuvant therapeutic procedures. The transcriptional regulators alpha thalassemia/mental retardation X-linked (ATRX) and death domain-associated protein (DAXX) have recently been described in different cancer entities as a useful prognostic biomarker. This study was initiated to explore their protein expression patterns and prognostic value in patients with ope ...[more]

PMID: 31374064

Similar Datasets

Project description:BACKGROUND: ATRX is a severe X-linked disorder characterized by mental retardation, facial dysmorphism, urogenital abnormalities and alpha-thalassemia. The disease is caused by mutations in ATRX gene, which encodes a protein belonging to the SWI/SNF DNA helicase family, a group of proteins involved in the regulation of gene transcription at the chromatin level. In order to identify specific genes involved in the pathogenesis of the disease, we compared, by cDNA microarray, the expression levels of approximately 8500 transcripts between ATRX and normal males of comparable age. METHODS: cDNA microarray was performed using total RNA from peripheral blood mononuclear cells of ATRX and normal males. Microarray results were validated by quantitative real-time polymerase chain reaction. RESULTS: cDNA microarray analysis showed that 35 genes had a lower expression (30-35% of controls) while 25 transcripts had a two-fold higher expression in comparison to controls. In the microarray results the probe for oligophrenin-1, a gene known for its involvement in mental retardation, showed a decreased hybridization signal. However, such gene was poorly expressed in blood mononuclear cells and its decrease was not confirmed in the quantitative real-time RT-PCR assay. On the other hand, the expression of an homologous gene, the GTPase regulator associated with the focal adhesion kinase 1/Oligophrenin-1-like (GRAF1/OPHN-1-L), was relatively high in blood mononuclear cells and significantly decreased in ATRX patients. The analysis of the expression pattern of the GRAF1/OPHN-1-L gene in human tissues and organs revealed the predominant brain expression of a novel splicing isoform, called variant-3. CONCLUSIONS: Our data support the hypothesis of a primary role for altered gene expression in ATRX syndrome and suggest that the GRAF1/OPHN-1-L gene might be involved in the pathogenesis of the mental retardation. Moreover a novel alternative splicing transcript of such gene, predominantly expressed in brain tissues, was identified.

Dataset Information

Expression and prognostic impact of alpha thalassemia/mental retardation X-linked and death domain-associated protein in human lung cancer.

Publications

Expression and prognostic impact of alpha thalassemia/mental retardation X-linked and death domain-associated protein in human lung cancer.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets