Expression of neural precursor cell expressed developmentally downregulated 4-1 in pancreatic cancer tissue and its clinical significance

Tingting BI; Sihui HOU; Yan LIU

doi:10.3969/j.issn.1001-5256.2022.03.024

Volume 38 Issue 3

Mar. 2022

Turn off MathJax

Article Contents

Article Navigation > Journal of Clinical Hepatology > 2022 > 38(3): 617-621

PDF( 3129 KB)

Expression of neural precursor cell expressed developmentally downregulated 4-1 in pancreatic cancer tissue and its clinical significance

DOI: 10.3969/j.issn.1001-5256.2022.03.024

Tingting BI^a,
Sihui HOU^a,
Yan LIU^{b
,
,
,}

a.
Department of Gastroenterology, Xuzhou Central Hospital Affiliated to Southeast University, Xuzhou, Jiangsu 221009, China
b.
Department of General Surgery, Xuzhou Central Hospital Affiliated to Southeast University, Xuzhou, Jiangsu 221009, China

Research funding:

Science and Technology Development Fund of Affiliated Hospital of Xuzhou Medical University (XYFC2020003)

More Information

Corresponding author: LIU Yan, liuyan880717@163.com(ORCID: 0000-0002-4827-3599)
Received Date: 2021-09-03
Accepted Date: 2021-09-28
Published Date: 2022-03-20

Abstract

Abstract

Objective To investigate the expression of the E3 ubiquitin ligase neural precursor cell expressed developmentally downregulated 4-1 (NEDD4-1) in pancreatic cancer tissue and its clinical significance. Methods Clinical data were collected from 58 patients who underwent surgical treatment in Xuzhou Central Hospital from January 2017 to December 2019 and were diagnosed with pancreatic ductal adenocarcinoma based on pathological examination. Immunohistochemistry was used to measure the expression of NEDD4-1 in pancreatic cancer tissue samples, and the association between the expression of NEDD4-1 and the clinicopathological features of pancreatic cancer was analyzed. Western blot was used to measure the protein expression level of NEDD4-1 in normal pancreatic ductal epithelial HPDE6-C7 cells and pancreatic cancer SW1990, BxPC-3, and PANC-1 cells. The t-test was used for comparison of continuous data between two groups, and the chi-square test was used for comparison of categorical data between two groups. The Kaplan-Meier method was used to plot survival curves, and the log-rank test was used for survival analysis. The Cox proportional-hazards regression model was used to investigate the factors associated with prognosis. Results The expression level of NEDD4-1 in pancreatic cancer tissue was significantly higher than that in adjacent tissue (79.31% vs 19.05%, χ²=35.614, P < 0.01), and the protein expression of NEDD4-1 in pancreatic cancer cells was significantly higher than that in normal pancreatic ductal epithelial cells (P < 0.01). In the patients with pancreatic cancer, the expression of NEDD4-1 was associated with distant metastasis (χ²=5.089, P=0.040), tumor differentiation (χ²=9.071, P=0.003), and TNM stage (χ²=8.882, P=0.003). The patients with high NEDD4-1 expression had a significantly shorter mean survival time than those with low expression (13.61±0.95 months vs 22.22±2.20 months, P=0.001). The Cox regression analysis showed that NEDD4-1 expression (hazard ratio [HR]=2.312, 95% confidence interval [CI]: 1.010-5.295, P=0.047), degree of tumor differentiation (HR=2.981, 95% CI: 1.556-5.712, P=0.001), and lymph node metastasis (HR=2.144, 95% CI: 1.155-3.979, P=0.016) were independent risk factors for the prognosis of patients with pancreatic cancer. Conclusion There is a significant increase in the expression of NEDD4-1 in pancreatic cancer tissue and cells, and the high expression of NEDD4-1 is associated with poor prognosis. Therefore, it can be used as a prognostic biomarker and a therapeutic target for pancreatic cancer.
- Pancreatic Neoplasms,
- Ubiquitin-Protein Ligases,
- Pathology, Clinical,
- Prognosis

FullText(HTML)

References(19)

References

[1]	SIEGEL RL, MILLER KD, JEMAL A. Cancer statistics, 2018[J]. CA Cancer J Clin, 2018, 68(1): 7-30. DOI: 10.3322/caac.21442.
[2]	CHEN W, ZHENG R, BAADE PD, et al. Cancer statistics in China, 2015[J]. CA Cancer J Clin, 2016, 66(2): 115-132. DOI: 10.3322/caac.21338.
[3]	SIEGEL RL, MILLER KD, JEMAL A. Cancer statistics, 2020[J]. CA Cancer J Clin, 2020, 70(1): 7-30. DOI: 10.3322/caac.21590.
[4]	SAAD AM, TURK T, AL-HUSSEINI MJ, et al. Trends in pancreatic adenocarcinoma incidence and mortality in the United States in the last four decades; a SEER-based study[J]. BMC Cancer, 2018, 18(1): 688. DOI: 10.1186/s12885-018-4610-4.
[5]	CHEN RF, ZHONG CR, ZHOU QB. Current status and perspectives of minimally invasive surgical treatment of pancreatic head carcinoma[J]. J Chin Hepatol, 2019, 35(5): 953-957. DOI: 10.3969/j.issn.1001-5256.2019.05.004. 陈汝福, 钟诚锐, 周泉波. 胰头癌微创手术治疗的现状及展望[J]. 临床肝胆病杂志, 2019, 35(5): 953-957. DOI: 10.3969/j.issn.1001-5256.2019.05.004.
[6]	GE WY, WANG HX. Immunotherapy for pancreatic ductal adenocarcinoma: Challenges and opportunities[J]. J Clin Hepatol, 2019, 35(5): 958-963. DOI: 10.3969/j.issn.1001-5256.2019.05.005. 葛伟玉, 王红霞. 胰腺导管腺癌的免疫治疗——挑战与机遇并存[J]. 临床肝胆病杂志, 2019, 35(5): 958-963. DOI: 10.3969/j.issn.1001-5256.2019.05.005.
[7]	CHEN Y, van de VIJVER MJ, HIBSHOOSH H, et al. PTEN and NEDD4 in human breast carcinoma[J]. Pathol Oncol Res, 2016, 22(1): 41-47. DOI: 10.1007/s12253-015-9971-2.
[8]	AMODIO N, SCRIMA M, PALAIA L, et al. Oncogenic role of the E3 ubiquitin ligase NEDD4-1, a PTEN negative regulator, in non-small-cell lung carcinomas[J]. Am J Pathol, 2010, 177(5): 2622-2634. DOI: 10.2353/ajpath.2010.091075.
[9]	SUN A, YU G, DOU X, et al. Nedd4-1 is an exceptional prognostic biomarker for gastric cardia adenocarcinoma and functionally associated with metastasis[J]. Mol Cancer, 2014, 13: 248. DOI: 10.1186/1476-4598-13-248.
[10]	YANG YM. Evaluation of American Joint Commission on Cancer (8^th edition) and Japanese Pancreas Society(7^th edition) changes for T and N staging in patients with pancreatic adenocarcinoma[J]. Chin J Surg, 2017, 55(1): 20-23. DOI: 10.3760/cma.j.issn.0529-5815.2017.01.006. 杨尹默. AJCC第八版及日本胰腺学会第七版胰腺癌TNM分期的更新要点及内容评介[J]. 中华外科杂志, 2017, 55(1): 20-23. DOI: 10.3760/cma.j.issn.0529-5815.2017.01.006.
[11]	WANG D, CUI M, YU J. Research advances of precision treatment for pancreatic cancer[J]. Chin J Dig Surg, 2021, 20(4): 385-394. DOI: 10.3760/cma.J.cn115610-20210223-00089. 汪栋, 崔铭, 余俊. 胰腺癌精准治疗的研究进展[J]. 中华消化外科杂志, 2021, 20(4): 385-394. DOI: 10.3760/cma.J.cn115610-20210223-00089.
[12]	WEI W, ZENG H, ZHENG R, et al. Cancer registration in China and its role in cancer prevention and control[J]. Lancet Oncol, 2020, 21(7): e342-342, e349. DOI: 10.1016/S1470-2045(20)30073-5.
[13]	FENG RM, ZONG YN, CAO SM, et al. Current cancer situation in China: Good or bad news from the 2018 Global Cancer Statistics?[J]. Cancer Commun (Lond), 2019, 39(1): 22. DOI: 10.1186/s40880-019-0368-6.
[14]	MAO N, HUANG ZJ, LIN ZT, et al. Current status of the application of translational medicine in the early diagnosis of pancreatic cancer[J]. Chin J Dig Surg, 2021, 20(4): 466-470. DOI: 10.3760/cma.j.cn115610-20210117-00029. 毛宁, 黄子健, 林志涛, 等. 转化医学在胰腺癌早期诊断中的应用现状[J]. 中华消化外科杂志, 2021, 20(4): 466-470. DOI: 10.3760/cma.j.cn115610-20210117-00029.
[15]	MOGK A, SCHMIDT R, BUKAU B. The N-end rule pathway for regulated proteolysis: Prokaryotic and eukaryotic strategies[J]. Trends Cell Biol, 2007, 17(4): 165-172. DOI: 10.1016/j.tcb.2007.02.001.
[16]	BALZAC F, AVOLIO M, DEGANI S, et al. E-cadherin endocytosis regulates the activity of Rap1: A traffic light GTPase at the crossroads between cadherin and integrin function[J]. J Cell Sci, 2005, 118(Pt 20): 4765-4783. DOI: 10.1242/jcs.02584.
[17]	YANG CL, LI QQ, XIA RL, et al. Effects of NEDD4 on proliferation, migration, and invasion of bladder cancer cells[J]. Shandong Med J, 2019, 59(16): 37-40. DOI: 10.3969/j.issn.1002-266X.2019.16.010. 杨传来, 李巧巧, 夏任兰, 等. NEDD4基因沉默对膀胱癌细胞增殖、迁移和侵袭的影响[J]. 山东医药, 2019, 59(16): 37-40. DOI: 10.3969/j.issn.1002-266X.2019.16.010.
[18]	LUHTALA S, STAFF S, KALLIONIEMI A, et al. Clinicopathological and prognostic correlations of HER3 expression and its degradation regulators, NEDD4-1 and NRDP1, in primary breast cancer[J]. BMC Cancer, 2018, 18(1): 1045. DOI: 10.1186/s12885-018-4917-1.
[19]	WENG M, LUO ZL, WU XL, et al. The E3 ubiquitin ligase NEDD4 is translationally upregulated and facilitates pancreatic cancer[J]. Oncotarget, 2017, 8(12): 20288-20296. DOI: 10.18632/oncotarget.15446.

Relative Articles

Supplements(0)

Cited By

Proportional views

Proportional views

通讯作者: 陈斌, bchen63@163.com

1.
沈阳化工大学材料科学与工程学院沈阳 110142

Figures(3) / Tables(2)

Get Citation

PDF

XML

Article Metrics

Article views (568) PDF downloads(38)

Expression of neural precursor cell expressed developmentally downregulated 4-1 in pancreatic cancer tissue and its clinical significance

DOI: 10.3969/j.issn.1001-5256.2022.03.024

Abstract

References

Proportional views

Catalog

通讯作者: 陈斌, bchen63@163.com

Article Metrics

Proportional views

Related

Expression of neural precursor cell expressed developmentally downregulated 4-1 in pancreatic cancer tissue and its clinical significance

DOI: 10.3969/j.issn.1001-5256.2022.03.024

Abstract

References

Proportional views

Catalog

通讯作者: 陈斌, bchen63@163.com

Article Metrics

Proportional views

Related

About Journal

Submission Guideline

Journal Online

Hepatobiliary College

Guidelines

Export File

Citation

Format

Content