Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
BMC Cancer
Published in: BMC Cancer 1/2016

Open Access 01-12-2016 | Research article

Clinicopathological and prognostic significance of GPX2 protein expression in esophageal squamous cell carcinoma

Authors: Zhijin Lei, Dongping Tian, Chong Zhang, Shukun Zhao, Min Su

Published in: BMC Cancer | Issue 1/2016

Login to get access

Abstract

Background

Chaoshan region, a littoral area of Guangdong province in southern China, has a high incidence of esophageal squamous cell carcinoma (ESCC). At present, the prognosis of ESCC is still very poor, therefore, there is urgent need to seek valuable molecular biomarker for prognostic evaluation to guide clinical treatment. GPX2, a selenoprotein, was exclusively expressed in gastrointestinal tract and has an anti-oxidative damage and anti-tumour effect in the progress of tumourigenesis.

Methods

We collected 161 ESCC patients samples, among which 83 patients were followed up. We employed immunochemistry analysis, western blotting and quantitative real-time PCR for measuring the expression of GPX2 within ESCC samples. We analysed the relationship between the expression of GPX2 and clinicopathological parameters of 161 patients with ESCC by Chi-square or Fisher’s exact test. The survival analysis of GPX2 expression within ESCC tissues was evaluated by the Kaplan-Meier method and Cox-regression.

Results

A significant higher expression level of GPX2 was detected in tumour tissues compared to that in non-tumour tissues (P < 0.001). Moreover, GPX2 expression has statistically significant difference in the tumour histological grade of ESCC (P < 0.001), while there was no statistically significant difference in age, sex, tumour size, tumour location, gross morphology and clinical TNM stages (P > 0.05). Meanwhile, the expression of GPX2 protein was obviously down-regulated within poorly differentiated ESCC. Last, survival analysis revealed that tumour histological grade and clinical TNM stages, both of the clinical pathological parameters of ESCC, were associated with the prognosis of patients with ESCC (respectively, P = 0.009, HR (95 % CI) = 1.885 (1.212 ~ 2.932); P = 0.007, HR (95 % CI) = 2.046 (1.318 ~ 3.177)). More importantly, loss expression of GPX2 protein predicted poor prognosis in patients with ESCC (P < 0.001, HR (95 % CI) = 5.700 (2.337 ~ 13.907)).

Conclusions

Collectively, these results suggested that the expression of GPX2 was significantly up-regulated within ESCC tumour tissues. GPX2 might be an important predictor for the prognosis of ESCC and a potential target for intervention and treatment of ESCC.
Appendix
Available only for authorised users
Literature
1.
Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61(2):69–90.CrossRefPubMed
2.
Peppelenbosch MP, Spaander MC, Bruno MJ. Glutathione peroxidase 7 prevents cancer in the oesophagus. Gut. 2014;63(4):537–8.CrossRefPubMed
3.
Toppo S, Vanin S, Bosello V, Tosatto SC. Evolutionary and structural insights into the multifaceted glutathione peroxidase (Gpx) superfamily. Antioxid Redox Signal. 2008;10(9):1501–14.CrossRefPubMed
4.
Brigelius-Flohe R, Maiorino M. Glutathione peroxidases. Biochim Biophys Acta. 2013;1830(5):3289–303.CrossRefPubMed
5.
Chu FF, Doroshow JH, Esworthy RS. Expression, characterization, and tissue distribution of a new cellular selenium-dependent glutathione peroxidase, GSHPx-GI. J Biol Chem. 1993;268(4):2571–6.PubMed
6.
Brigelius-Flohe R. Tissue-specific functions of individual glutathione peroxidases. Free Radic Biol Med. 1999;27(9-10):951–65.CrossRefPubMed
7.
Serewko MM, Popa C, Dahler AL, Smith L, Strutton GM, Coman W, Dicker AJ, Saunders NA. Alterations in gene expression and activity during squamous cell carcinoma development. Cancer Res. 2002;62(13):3759–65.PubMed
8.
Mork H, Scheurlen M, Al-Taie O, Zierer A, Kraus M, Schottker K, Jakob F, Kohrle J. Glutathione peroxidase isoforms as part of the local antioxidative defense system in normal and Barrett's esophagus. Int J Cancer. 2003;105(3):300–4.CrossRefPubMed
9.
Woenckhaus M, Klein-Hitpass L, Grepmeier U, Merk J, Pfeifer M, Wild P, Bettstetter M, Wuensch P, Blaszyk H, Hartmann A, et al. Smoking and cancer-related gene expression in bronchial epithelium and non-small-cell lung cancers. J Pathol. 2006;210(2):192–204.CrossRefPubMed
10.
Naiki-Ito A, Asamoto M, Hokaiwado N, Takahashi S, Yamashita H, Tsuda H, Ogawa K, Shirai T. Gpx2 is an overexpressed gene in rat breast cancers induced by three different chemical carcinogens. Cancer Res. 2007;67(23):11353–8.CrossRefPubMed
11.
Chiu ST, Hsieh FJ, Chen SW, Chen CL, Shu HF, Li H. Clinicopathologic correlation of up-regulated genes identified using cDNA microarray and real-time reverse transcription-PCR in human colorectal cancer. Cancer Epidemiol Biomarkers Prev. 2005;14(2):437–43.CrossRefPubMed
12.
Murawaki Y, Tsuchiya H, Kanbe T, Harada K, Yashima K, Nozaka K, Tanida O, Kohno M, Mukoyama T, Nishimuki E, et al. Aberrant expression of selenoproteins in the progression of colorectal cancer. Cancer Lett. 2008;259(2):218–30.CrossRefPubMed
13.
Suzuki S, Pitchakarn P, Ogawa K, Naiki-Ito A, Chewonarin T, Punfa W, Asamoto M, Shirai T, Takahashi S. Expression of glutathione peroxidase 2 is associated with not only early hepatocarcinogenesis but also late stage metastasis. Toxicology. 2013;311(3):115–23.CrossRefPubMed
14.
Naiki T, Naiki-Ito A, Asamoto M, Kawai N, Tozawa K, Etani T, Sato S, Suzuki S, Shirai T, Kohri K, et al. GPX2 overexpression is involved in cell proliferation and prognosis of castration-resistant prostate cancer. Carcinogenesis. 2014;35(9):1962–7.CrossRefPubMed
15.
Li ZS, Li Q. The latest 2010 WHO classification of tumors of digestive system. Zhonghua Bing Li Xue Za Zhi. 2011;40(5):351–4.PubMed
16.
Rice TW, Blackstone EH, Rusch VW. 7th edition of the AJCC Cancer Staging Manual: esophagus and esophagogastric junction. Ann Surg Oncol. 2010;17(7):1721–4.CrossRefPubMed
17.
Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 2001;25(4):402–8.CrossRefPubMed
18.
19.
Chen W, Zheng R, Zhang S, Zhao P, Zeng H, Zou X. Report of cancer incidence and mortality in China, 2010. Ann Transl Med. 2014;2(7):61.PubMedPubMedCentral
20.
Kamangar F, Dores GM, Anderson WF. Patterns of cancer incidence, mortality, and prevalence across five continents: defining priorities to reduce cancer disparities in different geographic regions of the world. J Clin Oncol. 2006;24(14):2137–50.CrossRefPubMed
21.
Andrici J, Eslick GD. Hot food and beverage consumption and the risk of esophageal cancer: a meta-analysis. Am J Prev Med. 2015;49(6):952–60.CrossRefPubMed
22.
Ursini F, Maiorino M, Brigelius-Flohe R, Aumann KD, Roveri A, Schomburg D, Flohe L. Diversity of glutathione peroxidases. Methods Enzymol. 1995;252:38–53.CrossRefPubMed
23.
Brigelius-Flohe R, Kipp AP. Physiological functions of GPx2 and its role in inflammation-triggered carcinogenesis. Ann N Y Acad Sci. 2012;1259:19–25.CrossRefPubMed
24.
Brigelius-Flohe R, Kipp A. Glutathione peroxidases in different stages of carcinogenesis. Biochim Biophys Acta. 2009;1790(11):1555–68.CrossRefPubMed
25.
Raza Y, Khan A, Farooqui A, Mubarak M, Facista A, Akhtar SS, Khan S, Kazi JI, Bernstein C, Kazmi SU. Oxidative DNA damage as a potential early biomarker of Helicobacter pylori associated carcinogenesis. Pathol Oncol Res. 2014;20(4):839–46.CrossRefPubMed
26.
Farinati F, Cardin R, Degan P, Rugge M, Mario FD, Bonvicini P, Naccarato R. Oxidative DNA damage accumulation in gastric carcinogenesis. Gut. 1998;42(3):351–6.CrossRefPubMedPubMedCentral
27.
Li K, Takezaki T, Lv LW, Yu P, Song FY, Tajima K. Reproducibility of a semi-quantitative food frequency questionnaire in Chaoshan area, China. Asian Pac J Cancer Prev. 2005;6(4):521–6.PubMed
28.
Su M, Liu M, Tian DP, Li XY, Yang HL, Huang HH, et al. Epidemiological investigating of the morbidity rate of malignant tumors and their diet habitats among residents of Nanao island in South China sea. J Environ Occup Med. 2005;22(4):312–6.
29.
Guangqi Y. Studies on human requirement of selenium. Chin J Endemiol. 1989;8(5):298–302.
Metadata
Title
Clinicopathological and prognostic significance of GPX2 protein expression in esophageal squamous cell carcinoma
Authors
Zhijin Lei
Dongping Tian
Chong Zhang
Shukun Zhao
Min Su
Publication date
01-12-2016
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2016
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-016-2462-3

Other articles of this Issue 1/2016

BMC Cancer 1/2016 Go to the issue

Research article

Impact on clinical practice of the implementation of guidelines for the toxicity management of targeted therapies in kidney cancer. The protect-2 study

Research article

Belotecan/cisplatin versus etoposide/cisplatin in previously untreated patients with extensive-stage small cell lung carcinoma: a multi-center randomized phase III trial

Research article

CT guided cryoablation for locally recurrent or metastatic bone and soft tissue tumor: initial experience

Research article

Growth hormone is increased in the lungs and enhances experimental lung metastasis of melanoma in DJ-1 KO mice

Research article

Retrospective and comparative analysis of 99mTc-Sestamibi breast specific gamma imaging versus mammography, ultrasound, and magnetic resonance imaging for the detection of breast cancer in Chinese women

Research article

The impact of breast cancer biological subtyping on tumor size assessment by ultrasound and mammography - a retrospective multicenter cohort study of 6543 primary breast cancer patients
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits