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Clinical significance of aberrant Wnt7a promoter methylation in human non-small cell lung cancer in Koreans.

Kim TH, Moon JY, Kim SH, Paik SS, Yoon HJ, Shin DH, Park SS, Sohn JW - J. Korean Med. Sci. (2015)

Bottom Line: In addition, Wnt7a promoter methylation showed correlation with loss of E-cadherin expression (P < 0.001).However, Wnt7a promoter methylation was not closely related with gender, age, histological type, or smoking habit.Even though Wnt7a methylation could not show significant correlation with the long term survival of the patients with limited follow up data, these findings suggest that loss of the Wnt7a gene induced by promoter methylation might be another prognostic factor for NSCLC and that restoration of Wnt7a may be a promising treatment for NSCLC.

View Article: PubMed Central - PubMed

Affiliation: Department of Internal Medicine, Hanyang University College of Medicine, Seoul, Korea.

ABSTRACT
The Wnt signaling pathway has regulatory roles in cell proliferation, differentiation, and polarity. Aberrant Wnt pathway regulation can lead to abnormal cell proliferation and cancer, and loss of Wnt7a expression has been demonstrated in lung cancer cell lines. E-cadherin keeps intercellular integrity and prevents metastasis. Therefore, E-cadherin has been known as a prognostic factor in cancer. In the present study, we investigated the E-cadherin expression status by immunohistochemical stain and the Wnt7a promoter methylation status in human non-small cell lung carcinoma (NSCLC) by methylation-specific PCR. We also analyzed their correlations with clinicopathological factors. Methylation of the Wnt7a gene promoter was detected in the lung tissues of 32 of 121 (26.4%) patients with NSCLC. Wnt7a promoter methylation was correlated with advanced tumor stage (P = 0.036) and distant metastasis (P = 0.037). In addition, Wnt7a promoter methylation showed correlation with loss of E-cadherin expression (P < 0.001). However, Wnt7a promoter methylation was not closely related with gender, age, histological type, or smoking habit. Even though Wnt7a methylation could not show significant correlation with the long term survival of the patients with limited follow up data, these findings suggest that loss of the Wnt7a gene induced by promoter methylation might be another prognostic factor for NSCLC and that restoration of Wnt7a may be a promising treatment for NSCLC.

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Related in: MedlinePlus

Representative results showing Wnt7a gene promoter methylation in non-small cell lung cancer tissues. Wnt7a gene promoter methylation status and corresponding unmethylated non-tumor tissue samples determined by methylation-specific PCR. Sample No. 1 shows promoter methylation. No. 2 is an unmethylated sample. A water blank was used as a negative control, and in vitro methylated genomic DNA was used as a positive control. M, PCR with Wnt7a primer for methylated DNA; U, PCR with primer for unmethylated DNA.
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Figure 2: Representative results showing Wnt7a gene promoter methylation in non-small cell lung cancer tissues. Wnt7a gene promoter methylation status and corresponding unmethylated non-tumor tissue samples determined by methylation-specific PCR. Sample No. 1 shows promoter methylation. No. 2 is an unmethylated sample. A water blank was used as a negative control, and in vitro methylated genomic DNA was used as a positive control. M, PCR with Wnt7a primer for methylated DNA; U, PCR with primer for unmethylated DNA.

Mentions: A methylation-specific PCR (MSP) assay was performed to determine the methylation status of the Wnt7a gene promoter in 121 NSCLC tissues. Fig. 2 shows representative MSP results. Of the 121 tumor tissue samples collected from patients with primary NSCLC, 32 (26.4%) showed methylation in the Wnt7a gene promoter region. We also performed MSP of Wnt7a in non-tumor lung tissue (50 of 121 samples) obtained from surgically resected specimens of patients with lung cancer. None of the 50 (0%) corresponding non-tumor tissue samples showed methylation in the Wnt7a promoter region.


Clinical significance of aberrant Wnt7a promoter methylation in human non-small cell lung cancer in Koreans.

Kim TH, Moon JY, Kim SH, Paik SS, Yoon HJ, Shin DH, Park SS, Sohn JW - J. Korean Med. Sci. (2015)

Representative results showing Wnt7a gene promoter methylation in non-small cell lung cancer tissues. Wnt7a gene promoter methylation status and corresponding unmethylated non-tumor tissue samples determined by methylation-specific PCR. Sample No. 1 shows promoter methylation. No. 2 is an unmethylated sample. A water blank was used as a negative control, and in vitro methylated genomic DNA was used as a positive control. M, PCR with Wnt7a primer for methylated DNA; U, PCR with primer for unmethylated DNA.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4310941&req=5

Figure 2: Representative results showing Wnt7a gene promoter methylation in non-small cell lung cancer tissues. Wnt7a gene promoter methylation status and corresponding unmethylated non-tumor tissue samples determined by methylation-specific PCR. Sample No. 1 shows promoter methylation. No. 2 is an unmethylated sample. A water blank was used as a negative control, and in vitro methylated genomic DNA was used as a positive control. M, PCR with Wnt7a primer for methylated DNA; U, PCR with primer for unmethylated DNA.
Mentions: A methylation-specific PCR (MSP) assay was performed to determine the methylation status of the Wnt7a gene promoter in 121 NSCLC tissues. Fig. 2 shows representative MSP results. Of the 121 tumor tissue samples collected from patients with primary NSCLC, 32 (26.4%) showed methylation in the Wnt7a gene promoter region. We also performed MSP of Wnt7a in non-tumor lung tissue (50 of 121 samples) obtained from surgically resected specimens of patients with lung cancer. None of the 50 (0%) corresponding non-tumor tissue samples showed methylation in the Wnt7a promoter region.

Bottom Line: In addition, Wnt7a promoter methylation showed correlation with loss of E-cadherin expression (P < 0.001).However, Wnt7a promoter methylation was not closely related with gender, age, histological type, or smoking habit.Even though Wnt7a methylation could not show significant correlation with the long term survival of the patients with limited follow up data, these findings suggest that loss of the Wnt7a gene induced by promoter methylation might be another prognostic factor for NSCLC and that restoration of Wnt7a may be a promising treatment for NSCLC.

View Article: PubMed Central - PubMed

Affiliation: Department of Internal Medicine, Hanyang University College of Medicine, Seoul, Korea.

ABSTRACT
The Wnt signaling pathway has regulatory roles in cell proliferation, differentiation, and polarity. Aberrant Wnt pathway regulation can lead to abnormal cell proliferation and cancer, and loss of Wnt7a expression has been demonstrated in lung cancer cell lines. E-cadherin keeps intercellular integrity and prevents metastasis. Therefore, E-cadherin has been known as a prognostic factor in cancer. In the present study, we investigated the E-cadherin expression status by immunohistochemical stain and the Wnt7a promoter methylation status in human non-small cell lung carcinoma (NSCLC) by methylation-specific PCR. We also analyzed their correlations with clinicopathological factors. Methylation of the Wnt7a gene promoter was detected in the lung tissues of 32 of 121 (26.4%) patients with NSCLC. Wnt7a promoter methylation was correlated with advanced tumor stage (P = 0.036) and distant metastasis (P = 0.037). In addition, Wnt7a promoter methylation showed correlation with loss of E-cadherin expression (P < 0.001). However, Wnt7a promoter methylation was not closely related with gender, age, histological type, or smoking habit. Even though Wnt7a methylation could not show significant correlation with the long term survival of the patients with limited follow up data, these findings suggest that loss of the Wnt7a gene induced by promoter methylation might be another prognostic factor for NSCLC and that restoration of Wnt7a may be a promising treatment for NSCLC.

Show MeSH
Related in: MedlinePlus