Expression and significance of NADPH oxidase DUOX1 in hepatocellular carcinoma after tumor resection

doi:10.3760/cma.j.issn.1674-0793.2010.01.104

Abstract

Abstract:

Objective

To study the prognostic value of dual oxidase 1(DUOX1) gene in hepatocellular carcinoma(HCC).

Methods

Reverse transcription polymerase chain reaction (RT-PCR) analysis were used to detect the expression of DUOX1 mRNA in 7 HCC cell lines, one normal liver cell line, specimen of normal liver tissues in 30 cases and paired specimen of neoplastic with matched adjacent non-neoplastic liver tissues in 103 cases. The correlation of the DUOX1 mRNA expression in neoplastic tissues were analyzed with clinicopathological and prognostic factors.

Results

DUOX1 mRNA was expressed in MHCC-97H, MHCC-97L and BEL7402 cell lines, but not in HepG2, Hep3B, SMMC-7721, Chang liver and LO2 cell line. The expression of DUOX1 mRNA was not found in all 30 normal liver tissues. The positive rates of DUOX1 expression in neoplastic tissues was higher than in adjacent non-neoplastic tissues(53.4% vs 14.5%, P <0.01), respectively. Univariate analysis indicated that factors affecting overall survival were gender, age, tumor size, satellite nodule, tumor thrombus in the portal vein, TNM stage and DUOX1 expression status in neoplastic tissues. Multivariate analysis indicated that independent factors affecting overall survival were tumor size, tumor thrombus in the portal vein and DUOX1 expression status.

Conclusions

DUOX1 expression in HCC neoplastic tissues is an independent factor affecting the prognosis of patients with HCC after tumor resection. DUOX1 may play a role in liver carcinogenesis.

Key words: NADPH oxidase, Hepatocellular Carcinoma, Prognosis, DUOX1

Can-liang LU, Pin-zhu HUANG, Bin-kui LI, Jian HONG, Liang HUANG, Li WANG, Ying ZHANG, Yun-fei YUAN. Expression and significance of NADPH oxidase DUOX1 in hepatocellular carcinoma after tumor resection[J]. Chinese Archives of General Surgery(Electronic Edition), 2010, 04(01): 10-15.

/ / Recommend

Add to citation manager EndNote|Ris|BibTeX

URL: https://zhptwkxwx.cma-cmc.com.cn/EN/10.3760/cma.j.issn.1674-0793.2010.01.104

https://zhptwkxwx.cma-cmc.com.cn/EN/Y2010/V04/I01/10

Figures/Tables 4

References 19

1	De Deken X, Wang D, Many MC, et al. Cloning of two human thyroid cDNAs encoding new members of the NADPH oxidase family. J Biol Chem, 2000, 275(30): 23 227-23 233.
2	Geiszt M, Witta J, Baffi J, et al. Dual oxidases represent novel hydrogen peroxide sources supporting mucosal surface host defense. FASEB J, 2003, 17(11): 1502-1504.
3	Liu LZ, Hu XW, Xia C, et al. Reactive oxygen species regulate epidermal growth factor-induced vascular endothelial growth factor and hypoxia-inducible factor-1alpha expression through activation of AKT and P70S6K1 in human ovarian cancer cells. Free Radic Biol Med, 2006, 41(10): 1521-1533.
4	Nishikawa M. Reactive oxygen species in tumor metastasis. Cancer Lett, 2008, 266(1): 53-59.
5	Xia C, Meng Q, Liu LZ, et al. Reactive oxygen species regulate angiogenesis and tumor growth through vascular endothelial growth factor. Cancer Res, 2007, 67(22): 10 823-10 830.
6	Yamaura M, Mitsushita J, Furuta S, et al. NADPH oxidase 4 contributes to transformation phenotype of melanoma cells by regulating G2-M cell cycle progression. Cancer Res, 2009, 69(6): 2647-2654.
7	Lee J K, Edderkaoui M, Truong P, et al. NADPH oxidase promotes pancreatic cancer cell survival via inhibiting JAK2 dephosphorylation by tyrosine phosphatases. Gastroenterology, 2007, 133(5): 1637-1648.
8	Shono T, Yokoyama N, Uesaka T, et al. Enhanced expression of NADPH oxidase Nox4 in human gliomas and its roles in cell proliferation and survival. Int J Cancer, 2008, 123(4): 787-792.
9	Vaquero EC, Edderkaoui M, Pandol SJ, et al. Reactive oxygen species produced by NAD(P)H oxidase inhibit apoptosis in pancreatic cancer cells. J Biol Chem, 2004, 279(33): 34 643-34 654.
10	Mochizuki T, Furuta S, Mitsushita J, et al. Inhibition of NADPH oxidase 4 activates apoptosis via the AKT/apoptosis signal-regulating kinase 1 pathway in pancreatic cancer PANC-1 cells. Oncogene, 2006, 25(26): 3699-3707.
11	Feig DI, Reid TM, Loeb LA. Reactive oxygen species in tumorigenesis. Cancer Res, 1994, 54(7 Suppl): 1890s-1894s.
12	Fruehauf JP, Meyskens FL, JR. Reactive oxygen species: a breath of life or death?. Clin Cancer Res, 2007, 13(3): 789-794.
13	Irani K, Xia Y, Zweier JL, et al. Mitogenic signaling mediated by oxidants in Ras-transformed fibroblasts. Science, 1997, 275(5306): 1649-1652.
14	Chiarugi P. Reactive oxygen species as mediators of cell adhesion. Ital J Biochem, 2003, 52(1): 28-32.
15	Van Rossen ME, Sluiter W, Bonthuis F, et al. Scavenging of reactive oxygen species leads to diminished peritoneal tumor recurrence. Cancer Res, 2000, 60(20): 5625-5629.
16	Lim SO, Gu JM, Kim MS, et al. Epigenetic changes induced by reactive oxygen species in hepatocellular carcinoma: methylation of the E-cadherin promoter. Gastroenterology, 2008,135(6):2128-2140, 40e1-8.
17	Ushio-Fukai M, Nakamura Y. Reactive oxygen species and angiogenesis: NADPH oxidase as target for cancer therapy. Cancer Lett, 2008, 266(1): 37-52.
18	Luxen S, Belinsky SA, Knaus UG. Silencing of DUOX NADPH oxidases by promoter hypermethylation in lung cancer. Cancer Res, 2008, 68(4): 1037-1045.
19	Clerkin JS, Naughton R, Quiney C, et al. Mechanisms of ROS modulated cell survival during carcinogenesis. Cancer Lett, 2008, 266(1): 30-36.

临床病理指标		DUOX1 mRNA表达状态[n(%)]		P值	例数	总体生存率(%)			P值
临床病理指标		阴性	阳性	P值	例数	1年	3年	5年	P值
性别		?	?	?	?	?	?	?	?
?	男	38(42.2)	52(57.8)	0.019^*	90	66.2	42.0	31.6	0.045^*
?	女	10(76.9)	3(23.2)	?	13	84.6	76.9	57.7	0.045^*
年龄(岁)		?	?	?	?	?	?	?	?
?	<50	18(35.3)	33(64.7)	0.023^*	51	59.9	37.7	25.2	0.042^*
?	≥50	30(57.7)	22(42.3)	?	52	78.8	54.8	38.4	0.042^*
HBsAg		?	?	?	?	?	?	?	?
?	阳性	43(45.3)	52(54.7)	0.468	95	70.2	46.3	29.5	0.744
?	阴性	5(62.5)	3(37.5)	?	8	50.0	50.0	50.0	0.744
肿瘤大小(cm)		?	?	?	?	?	?	?	?
?	<5	16(45.7)	19(54.3)	0.897	35	80.0	67.2	59.8	0.002^*
?	≥5	32(47.1)	36(52.9)	?	68	64.2	36.5	22.2	0.002^*
肿瘤包膜		?	?	?	?	?	?	?	?
?	无	13(40.6)	19(59.4)	0.661	32	75.0	50.0	37.5	0.220
?	不完整	23(51.1)	22(48.9)	?	45	63.4	41.6	26.7
?	完整	12(46.2)	14(53.8)	?	26	73.1	42.0	42.0
卫星结节		?	?	?	?	?	?	?	?
?	无	32(55.2)	26(44.8)	0.048^*	58	80.7	53.4	34.3	0.038^*
?	有	16(35.6)	29(64.4)	?	45	55.6	37.3	28.4	0.038^*
肝硬化		?	?	?	?	?	?	?	?
?	无/轻	25(45.5)	30(54.5)	0.803	55	72.6	50.4	39.6	0.411
?	中/重	23(47.9)	25(52.1)	?	48	66.0	42.5	24.3	0.411
AFP(μg/L)		?	?	?	?	?	?	?	?
?	<20	16(66.7)	8(33.3)	0.042^*	24	75.0	65.3	57.1	0.147
?	20~400	15(48.4)	16(51.6)	?	31	73.3	35.6	14.8
?	>400	17(35.4)	31(64.6)	?	48	60.2	45.1	36.5
癌栓		?	?	?	?	?	?	?	?
?	无	38(46.9)	43(53.1)	0.903	81	78.8	53.1	35.1	0.004^*
?	有	10(45.5)	12(545)	?	22	35.4	23.6	23.6	0.004^*
TNM分期		?	?	?	?	?	?	?	?
?	Ⅰ	20(42.6)	27(57.4)	0.725	47	80.5	60.0	40.9	0.004^*
?	Ⅱ	12(52.2)	11(47.8)	?	23	69.3	47.0	30.2
?	Ⅲ	16(48.5)	17(51.5)	?	33	51.5	27.6	22.1
Child-Pugh		?	?	?	?	?	?	?	?
?	A	40(47.6)	44(52.4)	0.663	84	68.6	47.2	33.0	0.764
?	B	8(42.1)	11(57.9)	?	19	68.4	44.9	44.9	0.764
DUOX1表达		?	?	?	?	?	?	?	?
?	阳性	-	-	-	55	57.5	36.4	32.3	0.026^*
?	阴性	-	-	-	48	83.2	58.0	44.1	0.026^*

临床病理指标		DUOX1 mRNA表达状态[n(%)]		P值	例数	总体生存率(%)			P值
临床病理指标		阴性	阳性	P值	例数	1年	3年	5年	P值
性别		?	?	?	?	?	?	?	?
?	男	38(42.2)	52(57.8)	0.019^*	90	66.2	42.0	31.6	0.045^*
?	女	10(76.9)	3(23.2)	?	13	84.6	76.9	57.7	0.045^*
年龄(岁)		?	?	?	?	?	?	?	?
?	<50	18(35.3)	33(64.7)	0.023^*	51	59.9	37.7	25.2	0.042^*
?	≥50	30(57.7)	22(42.3)	?	52	78.8	54.8	38.4	0.042^*
HBsAg		?	?	?	?	?	?	?	?
?	阳性	43(45.3)	52(54.7)	0.468	95	70.2	46.3	29.5	0.744
?	阴性	5(62.5)	3(37.5)	?	8	50.0	50.0	50.0	0.744
肿瘤大小(cm)		?	?	?	?	?	?	?	?
?	<5	16(45.7)	19(54.3)	0.897	35	80.0	67.2	59.8	0.002^*
?	≥5	32(47.1)	36(52.9)	?	68	64.2	36.5	22.2	0.002^*
肿瘤包膜		?	?	?	?	?	?	?	?
?	无	13(40.6)	19(59.4)	0.661	32	75.0	50.0	37.5	0.220
?	不完整	23(51.1)	22(48.9)	?	45	63.4	41.6	26.7
?	完整	12(46.2)	14(53.8)	?	26	73.1	42.0	42.0
卫星结节		?	?	?	?	?	?	?	?
?	无	32(55.2)	26(44.8)	0.048^*	58	80.7	53.4	34.3	0.038^*
?	有	16(35.6)	29(64.4)	?	45	55.6	37.3	28.4	0.038^*
肝硬化		?	?	?	?	?	?	?	?
?	无/轻	25(45.5)	30(54.5)	0.803	55	72.6	50.4	39.6	0.411
?	中/重	23(47.9)	25(52.1)	?	48	66.0	42.5	24.3	0.411
AFP(μg/L)		?	?	?	?	?	?	?	?
?	<20	16(66.7)	8(33.3)	0.042^*	24	75.0	65.3	57.1	0.147
?	20~400	15(48.4)	16(51.6)	?	31	73.3	35.6	14.8
?	>400	17(35.4)	31(64.6)	?	48	60.2	45.1	36.5
癌栓		?	?	?	?	?	?	?	?
?	无	38(46.9)	43(53.1)	0.903	81	78.8	53.1	35.1	0.004^*
?	有	10(45.5)	12(545)	?	22	35.4	23.6	23.6	0.004^*
TNM分期		?	?	?	?	?	?	?	?
?	Ⅰ	20(42.6)	27(57.4)	0.725	47	80.5	60.0	40.9	0.004^*
?	Ⅱ	12(52.2)	11(47.8)	?	23	69.3	47.0	30.2
?	Ⅲ	16(48.5)	17(51.5)	?	33	51.5	27.6	22.1
Child-Pugh		?	?	?	?	?	?	?	?
?	A	40(47.6)	44(52.4)	0.663	84	68.6	47.2	33.0	0.764
?	B	8(42.1)	11(57.9)	?	19	68.4	44.9	44.9	0.764
DUOX1表达		?	?	?	?	?	?	?	?
?	阳性	-	-	-	55	57.5	36.4	32.3	0.026^*
?	阴性	-	-	-	48	83.2	58.0	44.1	0.026^*

临床病理指标	β	SE	Hazard ratio(95% CI)	P值
性别	-0.579	0.548	0.560(0.191~1.640)	0.290
年龄(岁)	-0.006	0.013	0.994(0.968~1.020)	0.632
肿瘤大小(cm)	0.987	0.380	2.683(1.275~5.645)	0.009^*
卫星结节	-0.229	0.383	0.796(0.375~1.687)	0.551
癌栓	0.791	0.346	2.206(1.119~4.349)	0.022^*
TNM分期	0.204	0.254	1.226(0.744~2.019)	0.424
DUOX1表达状态	0.785	0.307	2.193(1.202~4.001)	0.010^*

临床病理指标	β	SE	Hazard ratio(95% CI)	P值
性别	-0.579	0.548	0.560(0.191~1.640)	0.290
年龄(岁)	-0.006	0.013	0.994(0.968~1.020)	0.632
肿瘤大小(cm)	0.987	0.380	2.683(1.275~5.645)	0.009^*
卫星结节	-0.229	0.383	0.796(0.375~1.687)	0.551
癌栓	0.791	0.346	2.206(1.119~4.349)	0.022^*
TNM分期	0.204	0.254	1.226(0.744~2.019)	0.424
DUOX1表达状态	0.785	0.307	2.193(1.202~4.001)	0.010^*

[1]	Miao Li, Lianhua Zhu, Peng Han, Bo Jiang, Xiang Fei. Evaluation of relationsip between vascular morphology and risk factors for hepatocellular carcinoma by high-frame-rate contrast-enhanced ultrasound [J]. Chinese Journal of Medical Ultrasound (Electronic Edition), 2023, 20(09): 911-915.
[2]	Jianmin Ding, Zhengyi Qin, Xiang Zhang, Yan Zhou, Hongyu Zhou, Yandong Wang, Xiang Jing. Contrast-enhanced ultrasound versus gadoxetic acid-enhanced magnetic resonance imaging for LI-RADS classification of focal liver lesions ≤3 cm in patients at high risk of hepatocellular carcinoma: a prospective study [J]. Chinese Journal of Medical Ultrasound (Electronic Edition), 2023, 20(09): 930-938.
[3]	Yuezhou Li, Kongxi Zhang, Xiaohong Li, Zhonghua Shang. Prognostic significance of PUM in gastric carcinoma based on bioinformatics analysis [J]. Chinese Archives of General Surgery(Electronic Edition), 2023, 17(06): 426-432.
[4]	Jie Dong, Song Yang, Hao Yang, Xiang Chen, Wanli Zhang. Relationship between hypermethylation of ACACB gene and clinicopathological factors and survival of hepatocellular carcinoma [J]. Chinese Archives of General Surgery(Electronic Edition), 2023, 17(06): 433-437.
[5]	Jun Zhang, Zai Luo, Mingyu Duan, Zhengjun Qiu, Chen Huang. Research progress of prognostic prediction models for gastric cancer [J]. Chinese Archives of General Surgery(Electronic Edition), 2023, 17(06): 456-461.
[6]	Qian Yang, Cuifang Li, Wanqiu Zhang. Analysis of short-term and long-term prognosis and influencing factors of primary liver cancer with spontaneous ruptured hemorrhage after emergency TACE surgery [J]. Chinese Journal of Operative Procedures of General Surgery(Electronic Edition), 2024, 18(01): 33-36.
[7]	Yansong Li, Huimin Feng, Mingchao Liu, Zepeng Liu, Qiuxia Jiang. Expression and clinical significance of STIP1 in triple negative breast cancer [J]. Chinese Journal of Operative Procedures of General Surgery(Electronic Edition), 2024, 18(01): 52-56.
[8]	Ming Jiang, Rui Luo, Chengchao Long. Diagnosis and treatment of obturator hernia: An experience of 73 cases over 10 years [J]. Chinese Journal of Hernia and Abdominal Wall Surgery(Electronic Edition), 2023, 17(06): 706-710.
[9]	Guangjun Zhong, Chunhua Liu, Wansen Zhu, Xiaolei Xu, Zhaojun Wang. Application of conventional MRI combined with different scanning sequences in preoperative staging diagnosis, chemotherapy efficacy and prognosis evaluation of gastric cancer [J]. Chinese Journal of Digestion and Medical Imageology(Electronic Edition), 2023, 13(06): 378-382.
[10]	Baoru Hu, Naijian Shang, Di Gao. DCE-MRI and DWI findings of advanced hepatocellular carcinoma and their correlation with prognosis after immunotherapy [J]. Chinese Journal of Digestion and Medical Imageology(Electronic Edition), 2023, 13(06): 399-403.
[11]	Fengyun Wu, Xin Teng, Lianjuan Liu. Diagnostic value of high-frequency ultrasonography and enhanced magnetic resonance for primary hyperdifferentiated hepatocellular carcinoma of different diameters [J]. Chinese Journal of Digestion and Medical Imageology(Electronic Edition), 2023, 13(06): 404-408.
[12]	Ping Lu, Jian Zou. Value of dynamic changes in coagulation and fibrinolytic markers in evaluating the prognosis of patients with acute pancreatitis [J]. Chinese Journal of Digestion and Medical Imageology(Electronic Edition), 2023, 13(06): 427-432.
[13]	Yongsheng Li, Jiahe Sun, Shuwei Guo, Yikang Lu, Hongzhou Liu. Short-term postoperative complications and their influencing factors in elderly patients with colorectal cancer [J]. Chinese Journal of Clinicians(Electronic Edition), 2023, 17(9): 962-967.
[14]	Jun Wang, Kunpeng Liu, Lan Yao, Hua Zhang, Yue Wei, Libin Suo, Jun Chen, chengli Miao, Chenghua Luo. Retrospective analysis of anesthesia management of massive transfusion patients undergoing retroperitoneal tumor resection [J]. Chinese Journal of Clinicians(Electronic Edition), 2023, 17(08): 844-849.
[15]	Libin Suo, Kunpeng Liu, Lan Yao, Hua Zhang, Yue Wei, Jun Wang, Jun Chen, Chengli Miao, Chenghua Luo. Key points of anesthesia management and prognostic factors in patients undergoing primary retroperitoneal paraganglioma resection [J]. Chinese Journal of Clinicians(Electronic Edition), 2023, 17(07): 771-776.

Please choose a citation manager

Content to export