Dataset Information

Quantitative assessment of the diagnostic role of FHIT promoter methylation in non-small cell lung cancer.

ABSTRACT: Aberrant methylation of CpG islands acquired in promoter regions plays an important role in carcinogenesis. Accumulated evidence demonstrates FHIT gene promoter hyper-methylation is involved in non-small cell lung cancer (NSCLC). To test the diagnostic ability of FHIT methylation status on NSCLC, thirteen studies, including 2,119 samples were included in our meta-analysis. Simultaneously, four independent DNA methylation datasets from TCGA and GEO database were analyzed for validation. The pooled odds ratio of FHIT promoter methylation in cancer samples was 3.43 (95% CI: 1.85 to 6.36) compared with that in controls. In subgroup analysis, significant difference of FHIT gene promoter methylation status in NSCLC and controls was found in Asians but not in Caucasian population. In validation stage, 950 Caucasian samples, including 126 paired samples from TCGA, 568 cancer tissues and 256 normal controls from GEO database were analyzed, and all 8 CpG sites near the promoter region of FHIT gene were not significantly differentially methylated. Thus the diagnostic role of FHIT gene in the lung cancer may be relatively limited in the Caucasian population but useful in the Asians.

SUBMITTER: Geng X

PROVIDER: S-EPMC5351674 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature

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Quantitative assessment of the diagnostic role of FHIT promoter methylation in non-small cell lung cancer.

Geng Xin X Pu Weilin W Tan Yulong Y Lu Zhouyi Z Wang An A Tan Lixing L Chen Sidi S Guo Shicheng S Wang Jiucun J Chen Xiaofeng X

Oncotarget 20170101 4

Aberrant methylation of CpG islands acquired in promoter regions plays an important role in carcinogenesis. Accumulated evidence demonstrates FHIT gene promoter hyper-methylation is involved in non-small cell lung cancer (NSCLC). To test the diagnostic ability of FHIT methylation status on NSCLC, thirteen studies, including 2,119 samples were included in our meta-analysis. Simultaneously, four independent DNA methylation datasets from TCGA and GEO database were analyzed for validation. The poole ...[more]

PMID: 28036263

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Project description:Interactions between cancer cells and the surrounding microenvironment are crucial determinants of cancer progression. During this process, bi-directional communication among tumor cells and cancer associated fibroblasts (CAF) regulate extracellular matrix (ECM) deposition and remodeling. As a result of this dynamic process, soluble ECM proteins can be released into the bloodstream and may represent novel circulating biomarkers useful for cancer diagnosis. The aim of the present study was to measure the levels of three circulating ECM related proteins (COL11A1, COL10A1 and SPARC) in plasma samples of lung cancer patients and in healthy heavy-smokers controls and test whether such measurements have diagnostic or prognostic value.Gene expression profiling of lung fibroblasts isolated from paired normal and cancer tissue of NSCLC patients was performed by gene expression microarrays. The prioritization of the candidates for the study of circulating proteins in plasma was based on the most differentially expressed genes in cancer associated fibroblasts. Soluble ECM proteins were assessed by western blot in the conditioned medium of lung fibroblasts and by ELISA assays in plasma samples.Plasma samples from lung cancer patients and healthy heavy-smokers controls were tested for levels of COL11A1 and COL10A1 (n?=?57 each) and SPARC (n?=?90 each). Higher plasma levels of COL10A1 were detected in patients (p???0.001), a difference that was driven specifically by females (p?<?0.001). No difference in COL11A1 levels between patients and controls was found. SPARC levels were also higher in plasma patients than controls (p?<?0.001) with good performance in discriminating the two groups (AUC?=?0.744). No significant association was observed between plasma proteins levels and clinicopathological features or survival.Soluble factors related to proficient tumor-stroma cross-talk are detectable in plasma of primary lung cancer patients and may represent a valuable complementary diagnostic tool to discriminate lung cancer patients from healthy heavy-smokers individuals as shown for the SPARC protein.

Dataset Information

Quantitative assessment of the diagnostic role of FHIT promoter methylation in non-small cell lung cancer.

Publications

Quantitative assessment of the diagnostic role of FHIT promoter methylation in non-small cell lung cancer.

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