Abnormal FHIT protein expression may be correlated with poor prognosis in gastric cancer: a meta-analysis

Wang, Heling; Zhou, Ping-Yi; Liu, Peng; Yu, Zhuang

doi:10.1007/s13277-014-1936-7

Cited by 10 publications

(12 citation statements)

References 26 publications

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“…Several investigators have shown that loss of FHIT function in preneoplastic lesions can lead to the accumulation of DNA damage and cell transformation; therefore it is defined as the guardian of the preneoplastic genome (12)(13)(14). Aberrant FHIT expression caused by truncated transcripts or promoter region hypermethylation has been found in esophageal, stomach, and colon carcinomas (7,15). Lack of FHIT expression in several studies was demonstrated to have impact on tumor aggressiveness (16).…”

Section: Introductionmentioning

confidence: 99%

FHIT promoter methylation status, low protein and high mRNA levels in patients with non-small cell lung cancer

Czarnecka

Migdalska-Sęk

Domańska

et al. 2016

International Journal of Oncology

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Abstract. FHIT is a tumor suppressor gene that is frequently silenced in non-small cell lung cancer (NSCLC) and also in preneoplastic lesions. Promoter hypermethylation was previously observed in NSCLC, and its epigenetic silencing, observed on mRNA or protein level, was proposed to predict NSCLC outcome. In the present study we evaluated the relationship between FHIT expression on mRNA level and promoter methylation, or immunoexpression level. The aim of this study was to analyze the usefulness of FHIT as early differentiating biomarker in NSCLC patients. Lung tissue specimens were obtained from 59 patients with diagnosed NSCLC (SCC=34, AC=20, LCC=5). FHIT promoter methylation was assessed in methylation-specific PCR. Relative expression analysis of FHIT was performed in real-time PCR (qPCR) and protein immunoexpression by ELISA assay. Significant differences in FHIT expression between NSCLC histopathological groups (SCC, AC, LCC) were observed (p=0.000009), with the lowest level in SCC. FHIT expression was significantly higher (p=0.034) in men vs. women. Methylated FHIT alleles were present both in NSCLC and control specimens. Mean MI value was higher in control tissue vs. neoplasm, and in men vs. women and it increased with patient age. Significant increase in MI level was observed in N0 group vs. N1 and N2, according to the TNM staging (p=0.0073). Differences in FHIT expression levels between AC, LCC and SCC indicated the usefulness of this gene as a diagnostic marker for NSCLC subtype differentiation. FHIT promoter hypermethylation both in cancer and control tissue indicated the presence of epigenetic alterations in early stage of NSCLC development.Differences in gene promoter methylation between cancer patients with and without node infiltration might be considered as a prognostic marker. Significantly lower FHIT protein immunoexpression was revealed in the group with long and intense history of smoking assessed as PYs (PY<40 vs. PY≥40, p=0.01). These results suggest the need of further study on FHIT as a potential biomarker.

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Section: Introductionmentioning

confidence: 99%

FHIT promoter methylation status, low protein and high mRNA levels in patients with non-small cell lung cancer

Czarnecka

Migdalska-Sęk

Domańska

et al. 2016

International Journal of Oncology

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“…FHIT loss was observed in 64% of non-small-cell lung cancer patients and was significantly associated with squamous cell carcinoma and poor tumor grade [10]. In addition, aberrant transcripts of FHIT have been found in other kinds of tumors, such as gastric [11], esophageal [12], and colon carcinomas [13]. FHIT has been recently seen as a genome caretaker which is of great importance for genome stability.…”

Section: Introductionmentioning

confidence: 99%

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

Geng

Tan

et al. 2016

Oncotarget

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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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“…In this group of large CFS genes, FHIT and PARK2 have been demonstrated to function as important tumor suppressors involved in the development of many different cancers [18] , [19] . Decreased FHIT expression has been shown to be associated with tumor progression in sporadic colon adenocarcinoma and poor prognosis in gastric cancer and oral squamous carcinoma [20] , [21] , [22] . PARK2 is commonly downregulated in clear-cell renal carcinoma and is associated with aggressive disease and a poor clinical outcome [23] .…”

Section: Discussionmentioning

confidence: 99%

Prognostic Significance of Decreased Expression of Six Large Common Fragile Site Genes in Oropharyngeal Squamous Cell Carcinomas

Gao¹,

Kasperbauer²,

Tombers³

et al. 2014

Translational Oncology

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Common fragile sites (CFSs) are large regions with profound genomic instability that often span extremely large genes a number of which have been found to be important tumor suppressors. RNA sequencing previously revealed that there was a group of six large CFS genes which frequently had decreased expression in oropharyngeal squamous cell carcinomas (OPSCCs) and real-time reverse transcriptase polymerase chain reaction experiments validated that these six large CFS genes (PARK2, DLG2, NBEA, CTNNA3, DMD, and FHIT) had decreased expression in most of the tumor samples. In this study, we investigated whether the decreased expression of these genes has any clinical significance in OPSCCs. We analyzed the six CFS large genes in 45 OPSCC patients and found that 27 (60%) of the OPSCC tumors had decreased expression of these six genes. When we correlated the expression of these six genes to each patient’s clinical records, for 11 patients who had tumor recurrence, 10 of them had decreased expression of almost all 6 genes. When we divided the patients into two groups, one group with decreased expression of the six genes and the other group with either slight changes or increased expression of the six genes, we found that there is significant difference in the incidence of tumor recurrence between these two groups by Kaplan-Meier plot analysis (P < .05). Our results demonstrated that those OPSCC tumors with decreased expression of this select group of six large CFS genes were much more likely to be associated with tumor recurrence and these genes are potential prognostic markers for predicting tumor recurrence in OPSCC.

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Abnormal FHIT protein expression may be correlated with poor prognosis in gastric cancer: a meta-analysis

Cited by 10 publications

References 26 publications

FHIT promoter methylation status, low protein and high mRNA levels in patients with non-small cell lung cancer

FHIT promoter methylation status, low protein and high mRNA levels in patients with non-small cell lung cancer

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

Prognostic Significance of Decreased Expression of Six Large Common Fragile Site Genes in Oropharyngeal Squamous Cell Carcinomas

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