The clinicopathological significance and drug target potential of FHIT in breast cancer, a meta-analysis and literature review.
FHIT is a bona fide tumor-suppressor gene and its loss contributes to tumorigenesis of epithelial cancers including breast cancer (BC). However, the association and clinicopathological significance between FHIT promoter hypermethylation and BC remains unclear. The purpose of this study is to conduct a meta-analysis and literature review to investigate the clinicopathological significance of FHIT methylation in BC. A detailed literature search was performed in PubMed, EMBASE, Web of Science, and Google Scholar databases. The data were extracted and assessed by two reviewers independently. Odds ratios with 95% corresponding confidence intervals were calculated. A total of seven relevant articles were available for meta-analysis, which included 985 patients. The frequency of FHIT hypermethylation was significantly increased in invasive ductal carcinoma compared to benign breast disease, the pooled odds ratio was 8.43, P<0.00001. The rate of FHIT hypermethylation was not significantly different between stage I/II and stage III/IV, odds ratio was 2.98, P=0.06. In addition, FHIT hypermethylation was not significantly associated with ER and PR status. FHIT hypermethylation was not significantly correlated with premenopausal and postmenopausal patients with invasive ductal carcinoma. In summary, our meta-analysis indicated that the frequency of FHIT hypermethylation was significantly increased in BC compared to benign breast disease. The rate of FHIT hypermethylation in advanced stages of BC was higher than in earlier stages; however, the difference was not statistically significant. Our data suggested that FHIT methylation could be a diagnostic biomarker of BC carcinogenesis. FHIT is a potential drug target for development of demethylation treatment for patients with BC.
Department of Cardiothoracic Surgery, Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China.
Yunshu
Y
Su
Department of Cardiothoracic Surgery, Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China ; Cancer Biology Research Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China.
Xiaoli
X
Wang
Department of Cardiothoracic Surgery, Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China.
Jun
J
Li
Department of General Surgery, Shanghai First People's Hospital, Shanghai Jiaotong University, Shanghai, People's Republic of China.
Junming
J
Xu
Department of Cardiothoracic Surgery, Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China.
Lijun
L
Xu
D017766:Acid Anhydride Hydrolases / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D016009:Chi-Square Distribution; D019175:DNA Methylation / Q000187:drug effects*; D055808:Drug Discovery / Q000379:methods*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D058990:Molecular Targeted Therapy; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D009367:Neoplasm Staging; D016017:Odds Ratio; D012307:Risk Factors; D015398:Signal Transduction / Q000187:drug effects; D000099170:Bis(5'-adenosyl)triphosphatase
D017766:Acid Anhydride Hydrolases; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; D000099170:Bis(5'-adenosyl)triphosphatase
FHIT; drug target; meta-analysis; methylation; odds ratio; tumor suppressor gene