Research Papers:

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

Xin Geng _, Weilin Pu, Yulong Tan, Zhouyi Lu, An Wang, Lixing Tan, Sidi Chen, Shicheng Guo, Jiucun Wang and Xiaofeng Chen

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Oncotarget. 2017; 8:6845-6856. https://doi.org/10.18632/oncotarget.14256

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Xin Geng1,*, Weilin Pu2,*, Yulong Tan1, Zhouyi Lu3, An Wang3, Lixing Tan2, Sidi Chen2, Shicheng Guo4, Jiucun Wang2, Xiaofeng Chen1

1Department of Cardiothoracic Surgery, Huashan Hospital, Fudan University, Shanghai 200032, China

2State Key Laboratory of Genetic Engineering, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University, Shanghai 200433, China

3Department of Chest Surgery, Shanghai Pulmonary Hospital, Shanghai 200433, China

4Department of Bioengineering, University of California at San Diego, La Jolla, CA 92093, USA

*These authors have contributed equally to this work

Correspondence to:

Shicheng Guo, email: [email protected]

Xiaofeng Chen, email: [email protected]

Jiucun Wang, email: [email protected]

Keywords: FHIT, DNA methylation, non-small cell lung cancer, NSCLC, diagnosis

Received: April 28, 2016     Accepted: December 12, 2016     Published: December 27, 2016


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.

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