Dataset Information

SHOX2 DNA methylation is a biomarker for the diagnosis of lung cancer based on bronchial aspirates.

ABSTRACT:

Background

This study aimed to show that SHOX2 DNA methylation is a tumor marker in patients with suspected lung cancer by using bronchial fluid aspirated during bronchoscopy. Such a biomarker would be clinically valuable, especially when, following the first bronchoscopy, a final diagnosis cannot be established by histology or cytology. A test with a low false positive rate can reduce the need for further invasive and costly procedures and ensure early treatment.

Methods

Marker discovery was carried out by differential methylation hybridization (DMH) and real-time PCR. The real-time PCR based HeavyMethyl technology was used for quantitative analysis of DNA methylation of SHOX2 using bronchial aspirates from two clinical centres in a case-control study. Fresh-frozen and Saccomanno-fixed samples were used to show the tumor marker performance in different sample types of clinical relevance.

Results

Valid measurements were obtained from a total of 523 patient samples (242 controls, 281 cases). DNA methylation of SHOX2 allowed to distinguish between malignant and benign lung disease, i.e. abscesses, infections, obstructive lung diseases, sarcoidosis, scleroderma, stenoses, at high specificity (68% sensitivity [95% CI 62-73%], 95% specificity [95% CI 91-97%]).

Conclusions

Hypermethylation of SHOX2 in bronchial aspirates appears to be a clinically useful tumor marker for identifying subjects with lung carcinoma, especially if histological and cytological findings after bronchoscopy are ambiguous.

SUBMITTER: Schmidt B

PROVIDER: S-EPMC2988753 | biostudies-literature | 2010 Nov

REPOSITORIES: biostudies-literature

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Publications

SHOX2 DNA methylation is a biomarker for the diagnosis of lung cancer based on bronchial aspirates.

Schmidt Bernd B Liebenberg Volker V Dietrich Dimo D Schlegel Thomas T Kneip Christoph C Seegebarth Anke A Flemming Nadja N Seemann Stefanie S Distler Jürgen J Lewin Jörn J Tetzner Reimo R Weickmann Sabine S Wille Ulrike U Liloglou Triantafillos T Raji Olaide O Walshaw Martin M Fleischhacker Michael M Witt Christian C Field John K JK

BMC cancer 20101103

<h4>Background</h4>This study aimed to show that SHOX2 DNA methylation is a tumor marker in patients with suspected lung cancer by using bronchial fluid aspirated during bronchoscopy. Such a biomarker would be clinically valuable, especially when, following the first bronchoscopy, a final diagnosis cannot be established by histology or cytology. A test with a low false positive rate can reduce the need for further invasive and costly procedures and ensure early treatment.<h4>Methods</h4>Marker d ...[more]

PMID: 21047392

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Project description:ObjectiveMethylation of the promoters of SHOX2 and RASSF1A are potentially informative biomarkers for the diagnosis of early lung adenocarcinoma (LUAD). Abnormal methylation of SHOX2 and RASSF1A promoters may promote the occurrence and facilitate the progression of LUAD.Materials and methodsWe selected 54 patients with early LUAD and 31 patients with benign lung nodules as a NJDT cohort and evaluated their DNA methylation and mRNA sequencing levels. The DNA methylation sequencing, mRNA sequencing, and clinical data for patients with LUAD were obtained from The Cancer Genome Atlas, and served as a TCGA cohort. We evaluated the diagnostic potential of a SHOX2 and RASSF1A combined promoter methylation assay for detection of early LUAD in the NJDT cohort. Then we explored the promoter methylation levels of SHOX2 and RASSF1A and their gene expression between normal and tumor samples at different stages in both cohorts. Pathways enriched between tumor and normal samples of methylation-positive patients in the NJDT cohort were analyzed.ResultsIn the NJDT cohort, the sensitivity of the combined promoter methylation assay on tumor samples was 74.07%, the sensitivity on paired tumor and paracancerous samples was 77.78%, and the specificities in both contexts were 100%. The combined promoter methylation-positive patients had clinicopathologic features including older age, larger tumors, deeper invasion, and higher Ki-67 expression. In both cohorts, SHOX2 expression increased and RASSF1A expression decreased in tumor samples. The promoter methylation level of SHOX2 and RASSF1A was significantly higher in tumor samples at stage I-II than that in normal samples. The promoter methylation levels of these two genes were both negative associated with their expression in early tumor samples. In the NJDT cohort, methylation-positive patients of both individual SHOX2 and RASSF1A assays exhibited upregulation of folate acid metabolism and nucleotide metabolism in tumor samples. The SHOX2 methylation-positive and RASSF1A methylation-positive patients showed the downregulation of pathways related to cell proliferation and apoptosis and pathways involved in DNA repair, cell growth and cell adhesion, respectively.ConclusionThe combined promoter methylation assay for SHOX2 and RASSF1A can be used for screening and diagnosis of early LUAD, with good sensitivity and specificity. The promoter methylation levels of SHOX2 and RASSF1A were associated with their abnormal mRNA expression, and affected DNA instability, cell proliferation, apoptosis and tumor microenvironment in patients with LUAD.

Dataset Information

SHOX2 DNA methylation is a biomarker for the diagnosis of lung cancer based on bronchial aspirates.

Background

Methods

Results

Conclusions

Publications

SHOX2 DNA methylation is a biomarker for the diagnosis of lung cancer based on bronchial aspirates.

Similar Datasets

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