Clinicopathological significance of WIF1 hypermethylation in NSCLC, a meta-analysis and literature review

Abstract

Methylation of the WIF-1 gene can lead to the loss of WIF-1 expression which has been observed in numerous types of cancer including NSCLC. However, the association and clinicopathological significance between WIF-1 promoter hypermethylation and NSCLC remains unclear. In the present study, we performed a meta-analysis to evaluate the clinicopathological significance of WIF-1 hypermethylation in NSCLC. A systematic literature search was carried out using Pubmed, EMBASE, Web of Science and CNKI. The Cochrane software Review manager 5.2 was used. The frequency of WIF-1 hypermethylation was significantly increased in NSCLC compared with normal lung tissue; the pooled OR was 8.67 with 95% CI 1.64-45.88, p = 0.01. The rate of WIF-1 hypermethylation was higher in SCC than in AC, OR was 1.74 with 95% CI 0.97-3.11, p = 0.06. In addition, WIF-1 loss was correlated with low 5-year survival rate. In summary, WIF-1 hypermethylation is a potential biomarker for diagnosis of NSCLC. WIF-1 hypermethylation is predominant in squamous cell carcinoma (SCC), suggesting that WIF-1 methylation contributes to the development of NSCLC, especially SCC.

Clinicopathological significance of CHFR methylation in non-small cell lung cancer: a systematic review and meta-analysis

“…Interestingly, present data showed that CHFR promoter methylation was associated with smoking behavior which is a risk factor for the development of SSC [ 38 ]. Similarly, previous reports indicated that alterations of Wif1, PTEN and TP53 gene were associated with smoking behavior [ 32 – 35 ], suggesting that smoking behavior may lead to the squamous cell carcinogenesis by inducing the inactivation of those suppressor genes including CHFR gene.…”

“…The molecular mechanism of pathogenesis is probably different between SCC and ADC. In addition, prior studies demonstrated that the loss of several suppressor genes such as Wnt inhibitory factor-1 ( Wif1 ) [ 32 ], Phosphatase and tensin homolog deleted on chromosome 10 ( PTEN ) [ 33 ] and TP53 [ 34 – 36 ] occurred more frequently in SSC than in ADC. P53 mutations were the most common one in SCC, occurring at 50% of cases, however there was no relationship between CHFR expression and p53 mutation [ 37 ], indicating CHFR may contribute the carcinogenesis of SCC independently.…”

Clinicopathological Significance and Diagnostic Value of <i>DLEC1</i> Hypermethylation in Lung Cancer: A Meta-analysis

“…In the meta-analysis, the results revealed that DLEC1 Previous studies demonstrated that the rate of WIF1 27 and CHFR 28 hypermethylation was higher in SCC than in AC. Our subgroup analysis revealed that the frequency of DLEC1 methylation was also significantly higher in SCC than AC, suggesting the usefulness of DLEC1 methylation as a biomarker in differentiating SCC and AC.…”

Mutation profiling in eight cases of vagal paragangliomas

“…For example, the CHST4 gene, which is associated with colon mucinous adenocarcinoma (MalaCards database); CLCA4 , a tumor suppressor gene encoding for the calcium-activated chloride channel A4 that can inhibit tumor cell proliferation, migration, and invasion [ 55 , 56 ]; ESR1 , characterized by mutations responsible for the resistance to endocrine therapy in breast cancer [ 57 ]; P2RY1 , involved in the regulation of multidrug chemoresistance of bladder cancer cells [ 58 ]; and PATZ1 , which acts as a tumor suppressor gene in thyroid cancer and is associated with the development of testicular tumors, sarcoma, and lung cancer [ 59 – 62 ]. Furthermore, we found alterations in the PRKCI gene related to many tumors [ 63 – 65 ] and WIF1 hypermethylation, frequently observed in cancer cells [ 66 – 69 ].…”