In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 71, No. 8_Supplement ( 2011-04-15), p. 4158-4158
Kurzfassung:
Analysis of DNA methylation at the SHOX2 locus has been shown to identify lung cancer in bronchial aspirates of patients with disease, and can potentially provide more definitive information to clinicians when histologic and cytologic findings from bronchoscopy are ambiguous. In a previous training study on bronchial aspirate samples, valid measurements were obtained from a total of 523 patient samples (242 controls, 281 cases). DNA methylation of SHOX2 discriminated malignant from benign lung disease (e.g. abscesses, infections, obstructive lung diseases, sarcoidosis, scleroderma, stenoses) with 68% sensitivity and 95% specificity. A SHOX2 assay performance was then validated in a blinded and randomized case control study comprised of Saccomanno-fixed bronchial lavage samples from 250 patients (125 cases, 125 controls). Results showed the SHOX2 assay reliably identified patients with lung cancer (AUC = 0.95, sensitivity 78%, specificity 96%). Computed tomography (CT) is currently being evaluated as a screening tool for early detection of lung cancer in several large ongoing trials. The randomized National Lung Screening Trial (NLST) in the United States was halted early after 8-year results showed that screening heavy smokers with low-dose helical CT significantly reduced deaths from lung cancer when compared with chest x-ray screening. However, CT scans fail to detect pre-invasive lesions and early lung cancer in the central airways, specifically small cell lung cancer (SCLC) and early stages of squamous cell carcinoma, which comprise 17-29% of all lung cancers. The use of a biomarker assay in conjunction with a CT might help to identify these patients. This study aimed to develop a modified SHOX2 assay which detects circulating methylated SHOX2 in blood and to analyze the performance of this optimized SHOX2 assay in plasma. Quantitative real-time PCR was used to analyze DNA methylation of SHOX2 assay in plasma samples from a total of 371 individuals (lung cancer patients, healthy individuals, benign lung diseases and prostate cancer patients). Performance of the assay was calculated to determine sensitivity and specificity based on a clinical cut-off. Valid measurements were obtained from a total of 343 patient samples (155 controls, 188 cases). DNA methylation of SHOX2 discriminated malignant lung disease from controls at a sensitivity of 62% and a specificity of 90%. SCLC (80%) and squamous cell carcinoma (63%) were detected at higher sensitivity as compared to adenocarcinoma (42%). SHOX2 DNA methylation is a sensitive and specific biomarker for detecting the presence of malignant lung disease in blood plasma, with highest sensitivity for detection of small cell and squamous cell lung cancer. A blood-based test for detection of SHOX2 DNA methylation could be a useful tool to identify patients with lung cancer alone or in conjunction with CT. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4158. doi:10.1158/1538-7445.AM2011-4158
Materialart:
Online-Ressource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/1538-7445.AM2011-4158
Sprache:
Englisch
Verlag:
American Association for Cancer Research (AACR)
Publikationsdatum:
2011
ZDB Id:
2036785-5
ZDB Id:
1432-1
ZDB Id:
410466-3
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