Expression of AMP-activated protein kinase/ten-eleven translocation 2 and their clinical relevance in colorectal cancer

被引:7
作者
Kang, Dong Hyun [1 ]
Jeong, Dong Jun [2 ,3 ]
Ahn, Tae Sung [1 ]
Lee, Hyun Yong [1 ]
Kim, Han Jo [4 ]
Bae, Sang Byung [4 ]
Kim, Hyeong Joo [2 ]
Lee, Moon Soo [6 ]
Kwon, Hyog Young [5 ]
Baek, Moo-Jun [1 ]
机构
[1] Soonchunhyang Univ, Div Colon & Rectal Surg, Dept Surg, Cheonan Hosp,Coll Med, 31 Suncheonhyang 6 Gil, Cheonan 31151, Chungcheongnam, South Korea
[2] Soonchunhyang Univ, Soonchunhyang Med Sci Res Inst, Cheonan Hosp, Coll Med, Cheonan 31151, Chungcheongnam, South Korea
[3] Soonchunhyang Univ, Dept Pathol, Cheonan Hosp, Coll Med, Cheonan 31151, Chungcheongnam, South Korea
[4] Soonchunhyang Univ, Dept Oncol, Cheonan Hosp, Coll Med, Cheonan 31151, Chungcheongnam, South Korea
[5] Soonchunhyang Univ, Soonchunhyang Inst Medi Bio Sci SIMS, Cheonan 31151, Chungcheongnam, South Korea
[6] Soonchunhyang Univ, Div Gastrointestinal Surg, Dept Surg, Coll Med, Cheonan 31151, Chungcheongnam, South Korea
关键词
AMP-activated protein kinase; ten-eleven translocation 2; colorectal cancer; biomarker; diabetes mellitus; DNA METHYLATION; KINASE EXPRESSION; PROSTATE-CANCER; 5-HYDROXYMETHYLCYTOSINE; IDH1;
D O I
10.3892/ol.2021.12425
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Inactivation of the ten-eleven translocation (TET) family members and catalyzation of 5-methylcytosine (5-mC) into 5-hydroxymethylcytosine (5-hmC) is associated with cancer initiation and progression. AMP-activated protein kinase (AMPK) is an enzyme that stabilizes TET2; however, the clinical relevance of AMPK and TET2 expression levels is currently unclear. Therefore, the present study aimed to investigate the clinical implications of AMPK/TET2 expression levels in colorectal cancer (CRC). Immunohistochemistry was used to retrospectively examine the expression levels of AMPK and TET2 in paraffin-embedded specimens obtained from 343 patients with CRC. The results demonstrated that AMPK and TET2 were highly expressed in CRC samples. No significant association was observed between the expression levels of TET2 and patient clinicopathological characteristics (age, tumor location, lymphatic, vascular and perineural invasion, Tumor-Node-Metastasis stages and differentiation); however, patients with low expression levels of TET2 more frequently presented with distant metastasis. By contrast, the expression levels of AMPK were significantly associated with lymph node and distant metastases. The survival analysis results revealed that high expression levels of TET2 were an independent predictor of favorable prognosis compared with low TET2 levels. However, no significant differences in overall survival were observed between patients with high and low expression levels of AMPK. These results described the clinical significance of AMPK/TET2 in CRC. The results of the multivariate analysis demonstrated that high expression levels of TET2 were a predictor of a favorable prognosis, whereas AMPK was not a significant factor for determining patient prognosis; therefore, further functional analysis of AMPK/TET2 expression in CRC is needed.
引用
收藏
页数:9
相关论文
共 39 条
[1]   Prognostic significance of AMP-activated protein kinase expression and modifying effect of MAPK3/1 in colorectal cancer [J].
Baba, Y. ;
Nosho, K. ;
Shima, K. ;
Meyerhardt, J. A. ;
Chan, A. T. ;
Engelman, J. A. ;
Cantley, L. C. ;
Loda, M. ;
Giovannucci, E. ;
Fuchs, C. S. ;
Ogino, S. .
BRITISH JOURNAL OF CANCER, 2010, 103 (07) :1025-1033
[2]   FBXL10 protects Polycomb-bound genes from hypermethylation [J].
Boulard, Mathieu ;
Edwards, John R. ;
Bestor, Timothy H. .
NATURE GENETICS, 2015, 47 (05) :479-U73
[3]  
Bray F, 2018, CA-CANCER J CLIN, V68, P394, DOI [10.3322/caac.21492, 10.3322/caac.21609]
[4]   Prognostic impact of AMP-activated protein kinase expression in ovarian carcinoma: Correlation of protein expression and GC/TOF-MS-based metabolomics [J].
Buckendahl, Ann-Christin ;
Budczies, Jan ;
Fiehn, Oliver ;
Darb-Esfahani, Silvia ;
Kind, Tobias ;
Noske, Aurelia ;
Weichert, Wilko ;
Sehouli, Jalid ;
Braicu, Elena ;
Dietel, Manfred ;
Denkert, Carsten .
ONCOLOGY REPORTS, 2011, 25 (04) :1005-1012
[5]   High NUAK1 expression correlates with poor prognosis and involved in NSCLC cells migration and invasion [J].
Chen, Peng ;
Li, Kai ;
Liang, Yan ;
Li, Liqing ;
Zhu, Xiaolin .
EXPERIMENTAL LUNG RESEARCH, 2013, 39 (01) :9-17
[6]   Methyltransferase recruitment and DNA hypermethylation of target promoters by an oncogenic transcription factor [J].
Di Croce, L ;
Raker, VA ;
Corsaro, M ;
Fazi, F ;
Fanelli, M ;
Faretta, M ;
Fuks, F ;
Lo Coco, F ;
Kouzarides, T ;
Nervi, C ;
Minucci, S ;
Pelicci, PG .
SCIENCE, 2002, 295 (5557) :1079-1082
[7]   The American Joint Committee on Cancer: the 7th Edition of the AJCC Cancer Staging Manual and the Future of TNM [J].
Edge, Stephen B. ;
Compton, Carolyn C. .
ANNALS OF SURGICAL ONCOLOGY, 2010, 17 (06) :1471-1474
[8]   Structural insight into autoinhibition and histone H3-induced activation of DNMT3A [J].
Guo, Xue ;
Wang, Ling ;
Li, Jie ;
Ding, Zhanyu ;
Xiao, Jianxiong ;
Yin, Xiaotong ;
He, Shuang ;
Shi, Pan ;
Dong, Liping ;
Li, Guohong ;
Tian, Changlin ;
Wang, Jiawei ;
Cong, Yao ;
Xu, Yanhui .
NATURE, 2015, 517 (7536) :640-U281
[9]   Histological evaluation of AMPK signalling in primary breast cancer [J].
Hadad, Sirwan M. ;
Baker, Lee ;
Quinlan, Philip R. ;
Robertson, Katherine E. ;
Bray, Susan E. ;
Thomson, George ;
Kellock, David ;
Jordan, Lee B. ;
Purdie, Colin A. ;
Hardie, David G. ;
Fleming, Stewart ;
Thompson, Alastair M. .
BMC CANCER, 2009, 9 :307
[10]  
Haffner MC, 2011, ONCOTARGET, V2, P627