The intracellular localization and clinical significance of HNF4α in tissues of colorectal cancer

doi:10.3969/j.issn.1673-8640.2013.03.012

Abstract

Abstract: Objective　To detect the intracellular localization and expression of hepatocyte nuclear factor-4 alpha (HNF4α) in tissues of colorectal cancer，and to investigate its relationship with clinical pathological parameters in patients with colorectal cancer. Methods　Immunohistochemistry was used to detect the intracellular localization and expression of HNF4α in 132 specimens of colorectal cancer tissues and adjacent normal intestinal mucosa. Results　The intracellular localization of HNF4α in colorectal cancer tissues was located in the cell plasma or in the cell nuclear. The positive rate of HNF4α expression in the cell plasma was significantly higher in colorectal cancer tissues than that in adjacent normal intestinal mucosa (76.5% and 3.8%，P＜0.05). The positive rate of HNF4α expression in the cell nuclear was significantly lower in colorectal cancer tissues than that in adjacent normal intestinal mucosa (12.9% and 64.4%，P＜0.05). The expression of HNF4α in the cell plasma of colorectal cancer tissues was related to tissue differentiation degree and Dukes staging(P＝0.02，P＝0.03)，but not to sex，age，tumor location，or lymph node metastasis(P＞0.05). Conclusions　The high expression of HNF4α in the cell plasma or low expression in the cell nuclear of colorectal cancer tissues is related with the development of colorectal cancer. The abnormal localization of HNF4α in colorectal cancer can serve as an objective index for the diagnosis and prognosis of colorectal cancer.

Key words: Hepatocyte nuclear factor-4 alpha, Intracellular localization, Immunohistochemistry, Colorectal cancer

ZHANG Liang 1，YUAN Huixiong 1，HUANG Yongzhi 2. The intracellular localization and clinical significance of HNF4α in tissues of colorectal cancer[J]. , 2013, 28(3): 215-217.

References

[1]Weltmeier F，Borlak J. A high resolution genome-wide scan of HNF4α recognition sites infers a regulatory gene network in colon cancer[J]. PLoS One，2011，6(7):e21667.
[2]龙云，唐红，刘聪，等.肝细胞核因子4α和3β在人主要器官中的表达[J].世界华人消化杂志，2006，14 (25) : 2504-2509.
[3]赵楚雄，魏宜胜，林秀娟.HNF-4α在结直肠癌组织中的表达及临床意义[J].广东医学，2011，32(9):1125-1127.
[4]Darsigny M，Babeu JP，Seidman EG，et al. Hepatocyte nuclear factor-4alpha promotes gut neoplasia in mice and protects against the production of reactive oxygen species[J].Cancer Res，2010，70(22):9423-9433.
[5]Chellappa K，Jankova L，Schnabl JM，et al. Src tyrosine kinase phosphorylation of nuclear receptor HNF4α correlates with isoform-specific loss of HNF4α in human colon cancer[J].Proc Natl Acad Sci USA，2012，109(7):2302-2307.
[6]Garrison WD，Battle MA，Yang C，et al. Hepatocyte nuclear factor 4alpha is essential for embryonic development of the mouse colon[J].Gastroenterology，2006，130(4):1207-1220. 
[7]陈金旭，韩英. 利用原子力显微镜观察大肠癌细胞与癌旁正常组织细胞[J]. 中国医疗前沿，2012，7(1):17-18.
[8]Schwartz B，Algamas-Dimantov A，Hertz R，et al．Inhibition of colorectal cancer by targeting hepatocyte nuclear factor- 4alpha[J].Int J Cancer，2009，124(5):1081-1089.
[9]宁北芳.肝细胞核因子4α预防大鼠肝癌及其分子机制研究[D].上海:第二军医大学，2009.
[10]Osanai M，Chiba H，Kojima T，Hepatocyte nuclear factor(HNF)-4alpha induces expression of endothelial Fas ligand (FasL) to prevent cancer cell transmigration: a novel defense mechanism of endothelium against cancer metastasis[J].Jpn J Cancer Res，2002，93(5):532-541.

[1]	HUANG Ren, SHI Weizhong, LU Renquan, GUO Lin, WANG Yanchun. Combined determination of Septin9 gene methylation and SDC2 gene methylation in auxiliary diagnosis of colorectal cancer [J]. Laboratory Medicine, 2025, 40(6): 519-524.
[2]	WU Yazhou, LI Hanhua, MENG Leijun, CHEN Xuefei, SUN Yuhan, WENG Wenhao, ZHENG Bing. Fusobacterium nucleatum promoting chemoresistance of colorectal cancer cells via lncRNA XIST [J]. Laboratory Medicine, 2025, 40(5): 428-436.
[3]	YU Jiajie, ZHANG Zhizhi, LUO Qingqiong, KE Xing. Predicting early colorectal tumor risk using a deep learning model based on multiple serum tumor markers [J]. Laboratory Medicine, 2025, 40(3): 253-258.
[4]	ZHENG Hui, CHEN Yingxiu, YE Lüyin, LU Renquan, GUO Lin. Relationship between peripheral blood T lymphocyte subsets and tumor progression in patients with colorectal cancer [J]. Laboratory Medicine, 2024, 39(4): 330-335.
[5]	XU Yunchuan, HUANGFU Yuchan, MA Yanhui. Effect of highly expressed IL-35 on Th1 and Th17 plasticity in colorectal cancer [J]. Laboratory Medicine, 2024, 39(4): 343-350.
[6]	ZOU Chen, XU Runhao, DING Yi, ZHANG Jie, WENG Wenhao, WANG Zhenhua, CAO Yun. Colorectal cancer screening model based on ProteomeXchange database [J]. Laboratory Medicine, 2024, 39(12): 1181-1189.
[7]	LAN Jun, LU Shuting, YANG Jianrui. Roles of serum IL-26 and IL-27 levels in patients with colorectal cancer [J]. Laboratory Medicine, 2024, 39(1): 7-12.
[8]	LI Liangshan, ZHAO Hu, WANG Shiwen. Screening potential prognostic biomarkers of colorectal cancer based on weighted gene co-expression network analysis [J]. Laboratory Medicine, 2023, 38(9): 825-832.
[9]	ZHU Rixiang, YIN Jie. Relationship between soluble growth stimulating gene 2 protein and clinicopathological features and prognosis in patients with colorectal cancer [J]. Laboratory Medicine, 2023, 38(7): 629-633.
[10]	JIANG Mengying, LIU Yiwen, HE Yiqing, XU Jing, YANG Cuixia, GAO Feng, DU Yan. Clinical role of serum S1P in the early diagnosis of colorectal cancer [J]. Laboratory Medicine, 2023, 38(4): 307-312.
[11]	ZHANG Guoliang, LIU Yiwen, HE Yiqing, XU Jing, YANG Cuixia, GAO Feng, LIU Hua. Roles of serum HYAL1 and HA in the auxiliary diagnosis and therapeutic monitoring of colorectal cancer [J]. Laboratory Medicine, 2023, 38(4): 313-319.
[12]	YANG Jielin, WANG Xiaoyuan, LI Haixia. Expression and interaction of TRX and TXNIP in colorectal cancer [J]. Laboratory Medicine, 2023, 38(4): 330-336.
[13]	ZHOU Furong, LI Yanzhu, LIU Yonggan. Application of lncRNA SNP in colorectal cancer susceptibility prediction and prognosis assessment [J]. Laboratory Medicine, 2023, 38(12): 1206-1210.
[14]	ZHU Yunjie, MA Zhengyao, SHEN Minna, ZHOU Yan, HUANG Fei, CHEN Xinning, ZHANG Chunyan, WANG Beili, GUO Wei. Establishment and clinical application evaluation of plasma cfDNA determination in colorectal cancer patients [J]. Laboratory Medicine, 2022, 37(6): 561-567.
[15]	GONG Zhiyun, JIANG Minglei, SHI Weizhong, LU Renquan, GUO Lin. Application value of fecal SDC2 gene methylation determination in the auxiliary diagnosis of colorectal cancer [J]. Laboratory Medicine, 2022, 37(4): 325-329.