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
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
BMC Medical Genetics
Published in: BMC Medical Genetics 1/2020

Open Access 01-12-2020 | Research article

Clinical significance and biological mechanisms of glutathione S-transferase mu gene family in colon adenocarcinoma

Authors: Erna Guo, Haotang Wei, Xiwen Liao, Liuyu Wu, Xiaoyun Zeng

Published in: BMC Medical Genetics | Issue 1/2020

Login to get access

Abstract

Background

Colon adenocarcinoma (COAD) is the most common form of colon cancer. The glutathione S-transferase Mu (GSTM) gene belongs to the GST gene family, which functions in cell metabolism and detoxification. The relationship between GSTM and COAD and the underlying mechanism remain unknown.

Methods

Data extracted from The Cancer Genome Atlas included mRNA expression and clinical information such as gender, age, and tumor stage. Prognostic values of GSTM genes were identified by survival analysis. Function and mechanism of prognostic GSTM genes were identified by gene set enrichment analysis. A nomogram was used to predict the contribution of risk factors to the outcome of COAD patients.

Results

Low expression of GSTM1 and GSTM2 was related to favorable OS (adjusted P = 0.006, adjusted HR = 0.559, 95% CI = 0.367–0.849 and adjusted P = 0.002, adjusted HR = 0.519, 95% CI = 0.342–0.790, respectively) after adjusting for tumor stage. Enrichment analysis also showed that genes involved were related to cell cycle, metabolism, and detoxification processes, as well as the Wnt signaling and NF-κB pathways.

Conclusions

In conclusion, low expression of GSTM1 and GSTM2 were significantly associated with favorable prognosis in COAD. These two genes may serve as potential biomarkers of COAD prognosis.
Appendix
Available only for authorised users
Literature
1.
2.
3.
4.
Cunningham D, Atkin W, Lenz HJ, Lynch HT, Minsky B, Nordlinger B, et al. Colorectal cancer. Lancet. 2010;375(9719):1030–47.PubMedCrossRef
5.
Dasari S, Ganjayi MS, Yellanurkonda P, Basha S, Meriga B. Role of glutathione S-transferases in detoxification of a polycyclic aromatic hydrocarbon, methylcholanthrene. Chem Biol Interact. 2018;294:81–90.PubMedCrossRef
6.
Hayes JD, Flanagan JU, Jowsey IR. Glutathione transferases. Annu Rev Pharmacol Toxicol. 2005;45:51–88.PubMedCrossRef
7.
8.
Pearson WR, Vorachek WR, Xu SJ, Berger R, Hart I, Vannais D, et al. Identification of class-mu glutathione transferase genes GSTM1-GSTM5 on human chromosome 1p13. Am J Hum Genet. 1993;53(1):220–33.PubMedPubMedCentral
9.
DeJong JL, Mohandas T, Tu CP. The human Hb (mu) class glutathione S-transferases are encoded by a dispersed gene family. Biochem Biophys Res Commun. 1991;180(1):15–22.PubMedCrossRef
10.
Mannervik B, Awasthi YC, Board PG, Hayes JD, Di Ilio C, Ketterer B, et al. Nomenclature for human glutathione transferases. Biochem J. 1992;282(Pt 1):305–6.PubMedPubMedCentralCrossRef
11.
Mannervik B, Board PG, Hayes JD, Listowsky I, Pearson WR. Nomenclature for mammalian soluble glutathione transferases. Methods Enzymol. 2005;401:1–8.PubMedCrossRef
12.
Tang Z, Li C, Kang B, Gao G, Li C, Zhang Z. GEPIA: a web server for cancer and normal gene expression profiling and interactive analyses. Nucleic Acids Res. 2017;45(W1):W98–W102.PubMedPubMedCentralCrossRef
13.
Huang da W, Sherman BT, Lempicki RA. Bioinformatics enrichment tools: paths toward the comprehensive functional analysis of large gene lists. Nucleic Acids Res 2009;37(1):1–13.
14.
Huang da W, Sherman BT, Lempicki RA. Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc 2009;4(1):44–57.
15.
Maere S, Heymans K, Kuiper M. BiNGO: a Cytoscape plugin to assess overrepresentation of gene ontology categories in biological networks. Bioinformatics. 2005;21(16):3448–9.PubMedCrossRef
16.
Warde-Farley D, Donaldson SL, Comes O, Zuberi K, Badrawi R, Chao P, et al. The GeneMANIA prediction server: biological network integration for gene prioritization and predicting gene function. Nucleic acids research. 2010;38(Web Server issue):W214–20.
17.
Szklarczyk D, Franceschini A, Wyder S, Forslund K, Heller D, Huerta-Cepas J, et al. STRING v10: protein-protein interaction networks, integrated over the tree of life. Nucleic Acids Res. 2015;43(Database issue):D447–52.PubMedCrossRef
18.
19.
Subramanian A, Tamayo P, Mootha VK, Mukherjee S, Ebert BL, Gillette MA, et al. Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci U S A. 2005;102(43):15545–50.PubMedPubMedCentralCrossRef
20.
Shannon P, Markiel A, Ozier O, Baliga NS, Wang JT, Ramage D, et al. Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res. 2003;13(11):2498–504.PubMedPubMedCentralCrossRef
21.
Laborde E. Glutathione transferases as mediators of signaling pathways involved in cell proliferation and cell death. Cell Death Differ. 2010;17(9):1373–80.PubMedCrossRef
22.
Hosono N, Kishi S, Iho S, Urasaki Y, Yoshida A, Kurooka H, et al. Glutathione S-transferase M1 inhibits dexamethasone-induced apoptosis in association with the suppression of Bim through dual mechanisms in a lymphoblastic leukemia cell line. Cancer Sci. 2010;101(3):767–73.PubMedCrossRef
23.
Csejtei A, Tibold A, Varga Z, Koltai K, Ember A, Orsos Z, et al. GSTM, GSTT and p53 polymorphisms as modifiers of clinical outcome in colorectal cancer. Anticancer Res. 2008;28(3B):1917–22.PubMed
24.
Medeiros R, Pereira D, Afonso N, Palmeira C, Faleiro C, Afonso-Lopes C, et al. Platinum/paclitaxel-based chemotherapy in advanced ovarian carcinoma: glutathione S-transferase genetic polymorphisms as predictive biomarkers of disease outcome. Int J Clin Oncol. 2003;8(3):156–61.PubMedCrossRef
25.
Howells RE, Holland T, Dhar KK, Redman CW, Hand P, Hoban PR, et al. Glutathione S-transferase GSTM1 and GSTT1 genotypes in ovarian cancer: association with p53 expression and survival. Int J Gynecol Cancer. 2001;11(2):107–12.PubMedCrossRef
26.
Fu XT, Song K, Zhou J, Shi YH, Liu WR, Tian MX, et al. Autophagy activation contributes to glutathione transferase mu 1-mediated chemoresistance in hepatocellular carcinoma. Oncol Lett. 2018;16(1):346–52.PubMedPubMedCentral
27.
Song K, Yi J, Shen X, Cai Y. Genetic polymorphisms of glutathione S-transferase genes GSTM1, GSTT1 and risk of hepatocellular carcinoma. PLoS One. 2012;7(11):e48924.PubMedPubMedCentralCrossRef
28.
Hall AG, Autzen P, Cattan AR, Malcolm AJ, Cole M, Kernahan J, et al. Expression of mu class glutathione S-transferase correlates with event-free survival in childhood acute lymphoblastic leukemia. Cancer Res. 1994;54(20):5251–4.PubMed
29.
Shen YH, Chen S, Peng YF, Shi YH, Huang XW, Yang GH, et al. Quantitative assessment of the effect of glutathione S-transferase genes GSTM1 and GSTT1 on hepatocellular carcinoma risk. Tumour Biol. 2014;35(5):4007–15.PubMedCrossRef
30.
Wang X, Huang ZH. Predictive potential role of glutathione S-transferase polymorphisms in the prognosis of breast cancer. Genet Mol Res. 2015;14(3):10236–41.PubMedCrossRef
31.
Ott K, Lordick F, Becker K, Ulm K, Siewert J, Hofler H, et al. Glutathione-S-transferase P1, T1 and M1 genetic polymorphisms in neoadjuvant-treated locally advanced gastric cancer: GSTM1-present genotype is associated with better prognosis in completely resected patients. Int J Color Dis. 2008;23(8):773–82.CrossRef
32.
Acevedo CA, Quinones LA, Catalan J, Caceres DD, Fulla JA, Roco AM. Impact of CYP1A1, GSTM1, and GSTT1 polymorphisms in overall and specific prostate cancer survival. Urol Oncol. 2014;32(3):280–90.PubMedCrossRef
33.
Anttila S, Hirvonen A, Vainio H, Husgafvel-Pursiainen K, Hayes JD, Ketterer B. Immunohistochemical localization of glutathione S-transferases in human lung. Cancer Res. 1993;53(23):5643–8.PubMed
34.
Giera S, Braeuning A, Kohle C, Bursch W, Metzger U, Buchmann A, et al. Wnt/beta-catenin signaling activates and determines hepatic zonal expression of glutathione S-transferases in mouse liver. Toxicol Sci. 2010;115(1):22–33.PubMedCrossRef
35.
Davalieva K, Kostovska IM, Kiprijanovska S, Markoska K, Kubelka-Sabit K, Filipovski V, et al. Proteomics analysis of malignant and benign prostate tissue by 2D DIGE/MS reveals new insights into proteins involved in prostate cancer. Prostate. 2015;75(14):1586–600.PubMedCrossRef
36.
Nishimura J, Dewa Y, Okamura T, Muguruma M, Jin M, Saegusa Y, et al. Possible involvement of oxidative stress in fenofibrate-induced hepatocarcinogenesis in rats. Arch Toxicol. 2008;82(9):641–54.PubMedCrossRef
37.
Tang SC, Wu MF, Wong RH, Liu YF, Tang LC, Lai CH, et al. Epigenetic mechanisms for silencing glutathione S-transferase m2 expression by hypermethylated specificity protein 1 binding in lung cancer. Cancer. 2011;117(14):3209–21.PubMedCrossRef
38.
Schnakenberg E, Breuer R, Werdin R, Dreikorn K, Schloot W. Susceptibility genes: GSTM1 and GSTM3 as genetic risk factors in bladder cancer. Cytogenet Cell Genet. 2000;91(1–4):234–8.PubMedCrossRef
39.
Liloglou T, Walters M, Maloney P, Youngson J, Field JK. A T2517C polymorphism in the GSTM4 gene is associated with risk of developing lung cancer. Lung Cancer. 2002;37(2):143–6.PubMedCrossRef
40.
Moyer AM, Sun Z, Batzler AJ, Li L, Schaid DJ, Yang P, et al. Glutathione pathway genetic polymorphisms and lung cancer survival after platinum-based chemotherapy. Cancer Epidemiol Biomark Prev. 2010;19(3):811–21.CrossRef
41.
Ionov Y, Peinado MA, Malkhosyan S, Shibata D, Perucho M. Ubiquitous somatic mutations in simple repeated sequences reveal a new mechanism for colonic carcinogenesis. Nature. 1993;363(6429):558–61.PubMedCrossRef
42.
Abdul Khalek FJ, Gallicano GI, Mishra L. Colon cancer stem cells. Gastrointest Cancer Res. 2010(Suppl 1):S16–23.
Metadata
Title
Clinical significance and biological mechanisms of glutathione S-transferase mu gene family in colon adenocarcinoma
Authors
Erna Guo
Haotang Wei
Xiwen Liao
Liuyu Wu
Xiaoyun Zeng
Publication date
01-12-2020
Publisher
BioMed Central
Published in
BMC Medical Genetics / Issue 1/2020
Electronic ISSN: 1471-2350
DOI
https://doi.org/10.1186/s12881-020-01066-2

Other articles of this Issue 1/2020

BMC Medical Genetics 1/2020 Go to the issue

Research article

A novel variant of IHH in a Chinese family with brachydactyly type 1

Research article

Effect of DNMT3A polymorphisms on CpG island hypermethylation in gastric mucosa

Case report

DGAT1 mutations leading to delayed chronic diarrhoea: a case report

Research article

ADIPOQ single nucleotide polymorphisms and breast cancer in northeastern Mexican women

Case report

Whole exome sequencing revealed a novel homozygous variant in the DGKE catalytic domain: a case report of familial hemolytic uremic syndrome

Case report

Identification of a novel WAS mutation in a South African patient presenting with atypical Wiskott-Aldrich syndrome: a case report