ZAK Gene Expression in Patients with Helicobacter pylori Infection.
Adenocarcinoma
/ genetics
Aged
Aged, 80 and over
Case-Control Studies
DNA, Complementary
/ metabolism
Gastric Mucosa
/ pathology
Gastritis
/ genetics
Gene Expression
Genotype
Helicobacter Infections
/ complications
Helicobacter pylori
Humans
MAP Kinase Kinase Kinases
/ genetics
Middle Aged
Stomach Neoplasms
/ genetics
Gastric antral epithelial cells
Gastric cancer
Gastritis
Gene expression
Helicobacter pylori
ZAK
Journal
Journal of gastrointestinal cancer
ISSN: 1941-6636
Titre abrégé: J Gastrointest Cancer
Pays: United States
ID NLM: 101479627
Informations de publication
Date de publication:
Jun 2022
Jun 2022
Historique:
accepted:
11
02
2021
pubmed:
24
2
2021
medline:
10
6
2022
entrez:
23
2
2021
Statut:
ppublish
Résumé
ZAK protein is a member of the MLK family proteins defined as mediators in the cell cycle. A survey of ZAK gene expression in gastric antral epithelial cells (GAECs) of gastritis and gastric adenocarcinoma patients with Helicobacter pylori genotypes infection can elucidate carcinogenesis of H. pylori genotypes. In a case-control study, ZAK gene expression was evaluated in GAECs biopsy samples of gastritis and gastric adenocarcinoma patients with (n 23, 21) and without H. pylori infection (n 27, 32), respectively. Total RNA was extracted from each gastric antral biopsy samples and cDNA synthesized by using Takara kits. H. pylori virulence genes֝ cDNA were detected by traditional PCR and specific primers. The ZAK gene expression was measured using the relative Real-Time RT PCR. The prevalence of gastric adenocarcinoma was the highest in man and 61-85 aged groups (p < .05). There was no significant correlation between the prevalence of H. pylori infection and patients' demographic groups. This study showed that ZAK gene overexpression gradually increases with increasing age and tumor grade among gastric adenocarcinoma patients. The gastric antral biopsy samples with H. pylori vacA s1m2 genotype infection showed a weak correlation with ZAK gene overexpression (p < .1). ZAK gene expression was higher in GAECs of gastritis cancer than in gastric adenocarcinoma, indicating the protective effect of ZAK against gastric cancer (p < .005). Reducing ZAK gene expression shows the negative correlations with H. pylori infection and gastric adenocarcinoma.
Sections du résumé
BACKGROUND
BACKGROUND
ZAK protein is a member of the MLK family proteins defined as mediators in the cell cycle. A survey of ZAK gene expression in gastric antral epithelial cells (GAECs) of gastritis and gastric adenocarcinoma patients with Helicobacter pylori genotypes infection can elucidate carcinogenesis of H. pylori genotypes.
METHODS
METHODS
In a case-control study, ZAK gene expression was evaluated in GAECs biopsy samples of gastritis and gastric adenocarcinoma patients with (n 23, 21) and without H. pylori infection (n 27, 32), respectively. Total RNA was extracted from each gastric antral biopsy samples and cDNA synthesized by using Takara kits. H. pylori virulence genes֝ cDNA were detected by traditional PCR and specific primers. The ZAK gene expression was measured using the relative Real-Time RT PCR.
RESULTS
RESULTS
The prevalence of gastric adenocarcinoma was the highest in man and 61-85 aged groups (p < .05). There was no significant correlation between the prevalence of H. pylori infection and patients' demographic groups. This study showed that ZAK gene overexpression gradually increases with increasing age and tumor grade among gastric adenocarcinoma patients. The gastric antral biopsy samples with H. pylori vacA s1m2 genotype infection showed a weak correlation with ZAK gene overexpression (p < .1).
CONCLUSION
CONCLUSIONS
ZAK gene expression was higher in GAECs of gastritis cancer than in gastric adenocarcinoma, indicating the protective effect of ZAK against gastric cancer (p < .005). Reducing ZAK gene expression shows the negative correlations with H. pylori infection and gastric adenocarcinoma.
Identifiants
pubmed: 33620708
doi: 10.1007/s12029-021-00611-3
pii: 10.1007/s12029-021-00611-3
doi:
Substances chimiques
DNA, Complementary
0
MAP Kinase Kinase Kinases
EC 2.7.11.25
MAP3K20 protein, human
EC 2.7.11.25
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
326-332Informations de copyright
© 2021. Springer Science+Business Media, LLC, part of Springer Nature.
Références
Hooi JKY, Lai WY, Ng WK, Suen MMY, Underwood FE, Tanyingoh D, Malfertheiner P, Graham DY, Wong VWS, Wu JCY, Chan FKL, Sung JJY, Kaplan GG, Ng SC. Global prevalence of Helicobacter pylori infection: systematic review and meta-analysis. Gastroenterology. 2017;153(2):420–9. https://doi.org/10.1053/j.gastro.2017.04.022 . (Epub 27 Apr 2017 PMID: 28456631).
doi: 10.1053/j.gastro.2017.04.022
pubmed: 28456631
Tran CT, Garcia M, Garnier M, Burucoa C, Bodet C. Inflammatory signaling pathways induced by Helicobacter pylori in primary human gastric epithelial cells. Innate Immun. 2017;23(2):165–74. https://doi.org/10.1177/1753425916681077 . (Epub 5 Dec 2016 PMID: 27913793).
doi: 10.1177/1753425916681077
pubmed: 27913793
Kao CY, Sheu BS, Wu JJ. Helicobacter pylori infection: An overview of bacterial virulence factors and pathogenesis. Biomed J. 2016;39(1):14–23. https://doi.org/10.1016/j.bj.2015.06 . Epub 1 Apr 2016 PMID: 27105595; PMCID: PMC6138426.
Jones KR, Whitmire JM, Merrell DS. A Tale of Two Toxins: Helicobacter Pylori CagA and VacA Modulate Host Pathways that Impact Disease. Front Microbiol. 2010;1:115.
Sue S, Shibata W, Maeda S. Helicobacter pylori-induced Signaling Pathways Contribute to Intestinal Metaplasia and Gastric Carcinogenesis. Biomed Res Int. 2015;2015:737621.
Krachler AM, Woolery AR, Orth K. Manipulation of kinase signaling by bacterial pathogens. J Cell Biol. 2011;195(7):1083–92. https://doi.org/10.1083/JCB.201107132 . Epub 28 Nov 2011 PMID: 22123833; PMCID: PMC3246894.
Yang JJ, Lee YJ, Hung HH, Tseng WP, Tu CC, Lee H, Wu WJ. ZAK inhibits human lung adenocarcinoma cell growth via ERK and JNK activation in an AP-1-dependent manner. Adenocarcinoma Sci. 2010;101(6):1374–81. https://doi.org/10.1111/j.1349-7006.2010.01537.x . (Epub 18 Feb 2010 PMID: 20331627).
doi: 10.1111/j.1349-7006.2010.01537.x
Braicu C, Buse M, Busuioc C, et al. A Comprehensive Review on MAPK: A Promising Therapeutic Target in Cancer. Cancers (Basel). 2019;11(10):1618. Published 22 Oct 2019. https://doi.org/10.3390/cancers11101618 .
Chmiela M, Karwowska Z, Gonciarz W, Allushi B, Stączek P. Host-pathogen interactions in Helicobacter pylori-related gastric cancer. World J Gastroenterol. 2017;23(9):1521–40. https://doi.org/10.3748/wjg.v23.i9.1521.PMID:28321154;PMCID:PMC5340805 .
doi: 10.3748/wjg.v23.i9.1521.PMID:28321154;PMCID:PMC5340805
pubmed: 28321154
pmcid: 5340805
Craige SM, Reif MM, Kant S. Mixed-lineage protein kinases (MLKs) in inflammation, metabolism, and other disease states. Biochim Biophys Acta. 2016;1862(9):1581–6. https://doi.org/10.1016/j.bbadis.2016.05.022 . (Epub 31 May 2016 PMID: 27259981).
doi: 10.1016/j.bbadis.2016.05.022
pubmed: 27259981
Jandhyala DM, Wong J, Mantis NJ, Magun BE, Leong JM, Thorpe CM. A novel zak knockout mouse with a defective ribotoxic stress response. Toxins (Basel). 2016;8(9):259. https://doi.org/10.3390/toxins8090259.PMID:27598200;PMCID:PMC5037485 .
doi: 10.3390/toxins8090259.PMID:27598200;PMCID:PMC5037485
Wong J, Smith LB, Magun EA, et al. Small molecule kinase inhibitors block the ZAK-dependent inflammatory effects of doxorubicin. Cancer Biol Ther. 2013;14(1):56–63. https://doi.org/10.4161/cbt.22628 .
doi: 10.4161/cbt.22628
pubmed: 23114643
pmcid: 3566053
Li L, Su N, Zhou T, et al. Mixed lineage kinase ZAK promotes epithelial-mesenchymal transition in cancer progression. Cell Death Dis. 2018;9(2):143. Published 2 Feb 2018. https://doi.org/10.1038/s41419-017-0161-x .
Zhan T, Rindtorff N, Boutros M. Wnt signaling in cancer. Oncogene. 2017;36(11):1461–73. https://doi.org/10.1038/onc.2016.304 .
doi: 10.1038/onc.2016.304
pubmed: 27617575
Polakis P. Wnt signaling in cancer. Cold Spring Harb Perspect Biol. 2012;4(5):a008052. Published 1 May 2012. https://doi.org/10.1101/cshperspect.a008052 .
Cui J, Yin Y, Ma Q, Wang G, Olman V, Zhang Y, Chou WC, Hong CS, Zhang C, Cao S, Mao X, Li Y, Qin S, Zhao S, Jiang J, Hastings P, Li F, Xu Y. Comprehensive characterization of the genomic alterations in human gastric cancer. Int J Cancer. 2015;137(1):86–95. https://doi.org/10.1002/ijc.29352 . Epub 3 Dec 2014 PMID: 25422082; PMCID: PMC4776643.
Rattanasinchai C, Gallo KA. MLK3 Signaling in Cancer Invasion. Cancers (Basel). 2016;8(5):51. Published 19 May 2016. https://doi.org/10.3390/cancers8050051 .
Rey C, Faustin B, Mahouche I, Ruggieri R, Brulard C, Ichas F, Soubeyran I, Lartigue L, De Giorgi F. The MAP3K ZAK, a novel modulator of ERK-dependent migration, is upregulated in colorectal cancer. Oncogene. 2016;35(24):3190–200. https://doi.org/10.1038/onc.2015.379 . Epub 2 Nov 2015 PMID: 26522728.
doi: 10.1038/onc.2015.379
pubmed: 26522728
M Ahmadi Hedayati, D Khani. Relationship of social risk factors and Helicobacter pylori infection with pathological characteristics of Gastric carcinoma. Iran J Med Microbiol. 20;14 (1):43–30.
Charan J, Biswas T. How to calculate sample size for different study designs in medical research? Indian J Psychol Med. 2013;35(2):121–6. https://doi.org/10.4103/0253-7176.116232 .
doi: 10.4103/0253-7176.116232
pubmed: 24049221
pmcid: 3775042
Nayak BK, Hazra A. How to choose the right statistical test? Indian J Ophthalmol. 2011;59(2):85–6. https://doi.org/10.4103/0301-4738.77005 .
doi: 10.4103/0301-4738.77005
pubmed: 21350275
pmcid: 3116565
Atherton JC, Cao P, Peek RM Jr, Tummuru MK, Blaser MJ, Cover TL. Cover Mosaicism in vacuolating cytotoxin alleles of Helicobacter pylori. Association of specific vacA types with cytotoxin production and peptic ulceration. J Biol Chem. 1995; 270:17771–17777.
van Doorn LJ1, Figueiredo C, Sanna R, Plaisier A, Schneeberger P, de Boer W, et al. Clinical relevance of the cagA, vacA, and iceA status of Helicobacter pylori. Gastroenterology. 1998; 115(1):58–66.
Sicinschi LA, Correa P, Bravo LE, et al. Non-invasive genotyping of Helicobacter pylori cagA, vacA, and hopQ from asymptomatic children. Helicobacter. 2012;17(2):96–106.
doi: 10.1111/j.1523-5378.2011.00919.x
Kralik P, Ricchi M. A Basic Guide to Real Time PCR in Microbial Diagnostics: Definitions, Parameters, and Everything. Front Microbiol. 2017;8:108. Published 2 Feb 2017. https://doi.org/10.3389/fmicb.2017.00108 .
Zhang XY, Zhang PY, Aboul-Soud MA. From inflammation to gastric cancer: role of Helicobacter pylori. Oncol Lett. 2017;13(2):543–8. https://doi.org/10.3892/ol.2016.5506 .
doi: 10.3892/ol.2016.5506
pubmed: 28356927
Kalali B, Mejias-Luque R, Javaheri A, Gerhard M. H. pylori virulence factors: influence on immune system and pathology. Mediators Inflamm. 2014;2014:426309.
Chmiela M, Kupcinskas J. Review: Pathogenesis of Helicobacter pylori infection. Helicobacter. 2019;24 Suppl 1(Suppl Suppl 1):e12638. https://doi.org/10.1111/hel.12638 .
Chiariotti L, Angrisano T, Keller S, Florio E, Affinito O, Pallante P, Perrino C, Pero R, Lembo F. Epigenetic modifications induced by Helicobacter pylori infection through a direct microbe-gastric epithelial cells cross-talk. Med Microbiol Immunol. 2013;202(5):327–37. https://doi.org/10.1007/s00430-013-0301-6 . (Epub 29 May 2013 PMID: 23715627).
doi: 10.1007/s00430-013-0301-6
pubmed: 23715627
Alzahrani S, Lina TT, Gonzalez J, Pinchuk IV, Beswick EJ, Reyes VE. Effect of Helicobacter pylori on gastric epithelial cells. World J Gastroenterol. 2014;20(36):12767–80. https://doi.org/10.3748/wjg.v20.i36.12767 .
doi: 10.3748/wjg.v20.i36.12767
pubmed: 25278677
pmcid: 4177462