Promoter hypermethylation of LGALS4 correlates with poor prognosis in patients with urothelial carcinoma

Meei Maan Wu, Ching Fei Li, Li Fang Lin, Alexander Sheng Shin Wang, Yeong Shiau Pu, Hsiu Hua Wang, Ai Chung Mar, Chien Jen Chen, Te Chang Lee

研究成果: 雜誌貢獻文章

4 引文 (Scopus)

摘要

Galectine-4 (gal-4), encoded by the LGALS4 gene, was recently shown to exhibit a tumor suppressive effect in colorectal carcinoma and pancreatic adenocarcinoma, although how the expression of this gene is regulated remains unknown. No reports describe the significance of gal-4 in the malignant potential of urothelial tumors. Thus, we analyzed LGALS4 methylation and gene expression and their clinical relevance and biological function in urothelial carcinoma (UC). LGALS4 methylation was initially identified as a progression biomarker for UC patients through genomewide DNA methylation profiling of 16 tumor samples. Bisulfite sequencing PCR and immunohistochemistry were performed to validate the promoter methylation and expression of LGALS4. We used quantitative methylation-specific PCR to determine the methylation levels of LGALS4 normalized to ACTB in the tumor samples of 79 UC patients and compared the levels between patients with different clinicopathological characteristics. The association with survival probability was analyzed with the Kaplan-Meier method and Cox regression analysis. The ectopic expression of gal-4 in cancer cell lines was used to address its biological function in UC in vitro. The promoter hypermethylation of LGALS4 (>2.51, log10 scale) revealed a positive correlation with high levels of both histological grade and tumor T category and with lymph node metastasis (all P=0.001). In addition, LGALS4 hypermethylation was an independent predictor of inferior survival in UC patients (P < 0.05). The ectopic expression studies demonstrated that gal-4 suppressed urothelial cancer cell growth, migration, and invasion. Thus, LGALS4 may function as a tumor suppressor gene in UC progression. Our findings provide evidence that methylation-mediated LGALS4 gene repression may be involved in urothelial tumor progression.
原文英語
頁(從 - 到)23787-23802
頁數16
期刊Oncotarget
8
發行號14
DOIs
出版狀態已發佈 - 一月 1 2017

指紋

Galectin 4
Carcinoma
Methylation
Neoplasms
Gene Expression
Polymerase Chain Reaction
Survival
DNA Fingerprinting
DNA Methylation
Tumor Suppressor Genes
Genes
Cell Movement
Colorectal Neoplasms
Adenocarcinoma

引用此文

Wu, M. M., Li, C. F., Lin, L. F., Wang, A. S. S., Pu, Y. S., Wang, H. H., ... Lee, T. C. (2017). Promoter hypermethylation of LGALS4 correlates with poor prognosis in patients with urothelial carcinoma. Oncotarget, 8(14), 23787-23802. https://doi.org/10.18632/oncotarget.15865

Promoter hypermethylation of LGALS4 correlates with poor prognosis in patients with urothelial carcinoma. / Wu, Meei Maan; Li, Ching Fei; Lin, Li Fang; Wang, Alexander Sheng Shin; Pu, Yeong Shiau; Wang, Hsiu Hua; Mar, Ai Chung; Chen, Chien Jen; Lee, Te Chang.

於: Oncotarget, 卷 8, 編號 14, 01.01.2017, p. 23787-23802.

研究成果: 雜誌貢獻文章

Wu, MM, Li, CF, Lin, LF, Wang, ASS, Pu, YS, Wang, HH, Mar, AC, Chen, CJ & Lee, TC 2017, 'Promoter hypermethylation of LGALS4 correlates with poor prognosis in patients with urothelial carcinoma', Oncotarget, 卷 8, 編號 14, 頁 23787-23802. https://doi.org/10.18632/oncotarget.15865
Wu, Meei Maan ; Li, Ching Fei ; Lin, Li Fang ; Wang, Alexander Sheng Shin ; Pu, Yeong Shiau ; Wang, Hsiu Hua ; Mar, Ai Chung ; Chen, Chien Jen ; Lee, Te Chang. / Promoter hypermethylation of LGALS4 correlates with poor prognosis in patients with urothelial carcinoma. 於: Oncotarget. 2017 ; 卷 8, 編號 14. 頁 23787-23802.
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abstract = "Galectine-4 (gal-4), encoded by the LGALS4 gene, was recently shown to exhibit a tumor suppressive effect in colorectal carcinoma and pancreatic adenocarcinoma, although how the expression of this gene is regulated remains unknown. No reports describe the significance of gal-4 in the malignant potential of urothelial tumors. Thus, we analyzed LGALS4 methylation and gene expression and their clinical relevance and biological function in urothelial carcinoma (UC). LGALS4 methylation was initially identified as a progression biomarker for UC patients through genomewide DNA methylation profiling of 16 tumor samples. Bisulfite sequencing PCR and immunohistochemistry were performed to validate the promoter methylation and expression of LGALS4. We used quantitative methylation-specific PCR to determine the methylation levels of LGALS4 normalized to ACTB in the tumor samples of 79 UC patients and compared the levels between patients with different clinicopathological characteristics. The association with survival probability was analyzed with the Kaplan-Meier method and Cox regression analysis. The ectopic expression of gal-4 in cancer cell lines was used to address its biological function in UC in vitro. The promoter hypermethylation of LGALS4 (>2.51, log10 scale) revealed a positive correlation with high levels of both histological grade and tumor T category and with lymph node metastasis (all P=0.001). In addition, LGALS4 hypermethylation was an independent predictor of inferior survival in UC patients (P < 0.05). The ectopic expression studies demonstrated that gal-4 suppressed urothelial cancer cell growth, migration, and invasion. Thus, LGALS4 may function as a tumor suppressor gene in UC progression. Our findings provide evidence that methylation-mediated LGALS4 gene repression may be involved in urothelial tumor progression.",
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AU - Wu, Meei Maan

AU - Li, Ching Fei

AU - Lin, Li Fang

AU - Wang, Alexander Sheng Shin

AU - Pu, Yeong Shiau

AU - Wang, Hsiu Hua

AU - Mar, Ai Chung

AU - Chen, Chien Jen

AU - Lee, Te Chang

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N2 - Galectine-4 (gal-4), encoded by the LGALS4 gene, was recently shown to exhibit a tumor suppressive effect in colorectal carcinoma and pancreatic adenocarcinoma, although how the expression of this gene is regulated remains unknown. No reports describe the significance of gal-4 in the malignant potential of urothelial tumors. Thus, we analyzed LGALS4 methylation and gene expression and their clinical relevance and biological function in urothelial carcinoma (UC). LGALS4 methylation was initially identified as a progression biomarker for UC patients through genomewide DNA methylation profiling of 16 tumor samples. Bisulfite sequencing PCR and immunohistochemistry were performed to validate the promoter methylation and expression of LGALS4. We used quantitative methylation-specific PCR to determine the methylation levels of LGALS4 normalized to ACTB in the tumor samples of 79 UC patients and compared the levels between patients with different clinicopathological characteristics. The association with survival probability was analyzed with the Kaplan-Meier method and Cox regression analysis. The ectopic expression of gal-4 in cancer cell lines was used to address its biological function in UC in vitro. The promoter hypermethylation of LGALS4 (>2.51, log10 scale) revealed a positive correlation with high levels of both histological grade and tumor T category and with lymph node metastasis (all P=0.001). In addition, LGALS4 hypermethylation was an independent predictor of inferior survival in UC patients (P < 0.05). The ectopic expression studies demonstrated that gal-4 suppressed urothelial cancer cell growth, migration, and invasion. Thus, LGALS4 may function as a tumor suppressor gene in UC progression. Our findings provide evidence that methylation-mediated LGALS4 gene repression may be involved in urothelial tumor progression.

AB - Galectine-4 (gal-4), encoded by the LGALS4 gene, was recently shown to exhibit a tumor suppressive effect in colorectal carcinoma and pancreatic adenocarcinoma, although how the expression of this gene is regulated remains unknown. No reports describe the significance of gal-4 in the malignant potential of urothelial tumors. Thus, we analyzed LGALS4 methylation and gene expression and their clinical relevance and biological function in urothelial carcinoma (UC). LGALS4 methylation was initially identified as a progression biomarker for UC patients through genomewide DNA methylation profiling of 16 tumor samples. Bisulfite sequencing PCR and immunohistochemistry were performed to validate the promoter methylation and expression of LGALS4. We used quantitative methylation-specific PCR to determine the methylation levels of LGALS4 normalized to ACTB in the tumor samples of 79 UC patients and compared the levels between patients with different clinicopathological characteristics. The association with survival probability was analyzed with the Kaplan-Meier method and Cox regression analysis. The ectopic expression of gal-4 in cancer cell lines was used to address its biological function in UC in vitro. The promoter hypermethylation of LGALS4 (>2.51, log10 scale) revealed a positive correlation with high levels of both histological grade and tumor T category and with lymph node metastasis (all P=0.001). In addition, LGALS4 hypermethylation was an independent predictor of inferior survival in UC patients (P < 0.05). The ectopic expression studies demonstrated that gal-4 suppressed urothelial cancer cell growth, migration, and invasion. Thus, LGALS4 may function as a tumor suppressor gene in UC progression. Our findings provide evidence that methylation-mediated LGALS4 gene repression may be involved in urothelial tumor progression.

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