Document Type : Original Article

Authors

1 Department of Medicine, College of Medicine, Misan University, Amarah, Maysan, Iraq

2 Department of Agronomy and Plant Breeding, Faculty of Agriculture and Natural Resources, University of Mohaghegh Ardabili, Ardabil, Iran

3 Department of Chemistry and Biochemistry, College of Medicine, Misan University, Amarah, Maysan, Iraq

Abstract

Gastric cancer is the abnormal growth of stomach cells. The symptoms of this disease include difficulty in swallowing, heartburn, stomach pain, indigestion, nausea, vomiting, and blood in the stool. Gastric cancer is a multifactorial and genetic disease, and many genes and factors are involved in it. DCC and CDH1 are the genes silenced by hypermethylation in gastric cancer and play an influential role in suppressing gastric cancer tumors. The aim of this study was bioinformatics analysis at the genome and proteome level and evaluation and comparison of the expression of DCC and CDH1 genes in different human body tissues. The results of this study showed that the CDH1 gene is more expressed in the thyroid gland and Parathyroid gland and the DCC gene is more expressed in the testis, hippocampal formation, basal ganglia, midbrain, cerebral cortex, and hypothalamus. The expression analysis of these genes showed that both genes generally are more active in glands and have little expression in other body organs. Cellular analysis of DCC and CDH1 genes by antibodies that bind to the proteins of the target genes showed that both genes are active in the Golgi apparatus, with the difference that the DCC gene is more present in the nucleus and the CDH1 gene is more present in the plasma membrane. The expression level of the CDH1 gene is relatively higher than that of the DCC gene. Also, phenotypic studies of the DCC gene showed that this gene is related to colorectal cancer, and it was found that the CDH1 gene is effective in Blepharocheilodontic syndrome 1. Finally, considering the role of CDH1 and DCC genes as tumor suppressor genes, these items can be used for targeted treatments in gastric cancer.

Graphical Abstract

Molecular and clinical analysis of genes involved in gastric cancer

Keywords

Main Subjects

Selected author of this article by journal

Dr. Redha Alwan Hasan
Misan University
Google Scholar

Open Access

This article is licensed under a CC BY License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit: http://creativecommons.org/licenses/by/4.0/

 

Publisher’s Note

CMBR journal remains neutral with regard to jurisdictional claims in published maps and institutional afflictions.

 

Letters to Editor

Given that CMBR Journal's policy in accepting articles will be strict and will do its best to ensure that in addition to having the highest quality published articles, the published articles should have the least similarity (maximum 15%). Also, all the figures and tables in the article must be original and the copyright permission of images must be prepared by authors. However, some articles may have flaws and have passed the journal filter, which dear authors may find fault with. Therefore, the editor of the journal asks the authors, if they see an error in the published articles of the journal, to email the article information along with the documents to the journal office.

CMBR Journal welcomes letters to the editor ([email protected], [email protected]) for the post-publication discussions and corrections which allows debate post publication on its site, through the Letters to Editor. Critical letters can be sent to the journal editor as soon as the article is online. Following points are to be considering before sending the letters (comments) to the editor.

[1] Letters that include statements of statistics, facts, research, or theories should include appropriate references, although more than three are discouraged.

[2] Letters that are personal attacks on an author rather than thoughtful criticism of the author’s ideas will not be considered for publication.

[3] There is no limit to the number of words in a letter.

[4] Letter writers should include a statement at the beginning of the letter stating that it is being submitted either for publication or not.

[5] Anonymous letters will not be considered.

[6] Letter writers must include Name, Email Address, Affiliation, mobile phone number, and Comments.

[7] Letters will be answered as soon as possible.

  1. Arnold M, Abnet CC, Neale RE, Vignat J, Giovannucci EL, McGlynn KA, Bray F (2020) Global burden of 5 major types of gastrointestinal cancer. Gastroenterology 159(1):335-349. e315. doi:https://doi.org/10.1053/j.gastro.2020.02.068
  2. Rezaei-Nasab M, Komeili G, Fazeli-Nasab B (2017) Gastroprotective effects of aqueous and hydroalcholic extract of Scrophularia striata on ethanol-induced gastric ulcers in rats. Der Pharmacia Lettre 9(5):84-93
  3. Shore R, Yu J, Ye W, Lagergren J, Rutegård M, Akre O, Stattin P, Lindblad M (2021) Risk of esophageal and gastric adenocarcinoma in men receiving androgen deprivation therapy for prostate cancer. Scientific reports 11(1):13486. doi:https://doi.org/10.1038/s41598-021-92347-0
  4. Maselli DB, Camilleri M (2021) Pharmacology, clinical effects, and therapeutic potential of cannabinoids for gastrointestinal and liver diseases. Clinical Gastroenterology and Hepatology 19(9):1748-1758. e1742. doi:https://doi.org/10.1016/j.cgh.2020.04.020
  5. Fuchs CS, Mayer RJ (1995) Gastric carcinoma. New England Journal of Medicine 333(1):32-41. doi:https://doi.org/10.1056/NEJM199507063330107
  6. Brisset M, Grandin Ml, Bernet A, Mehlen P, Hollande Fdr (2021) Dependence receptors: new targets for cancer therapy. EMBO Molecular Medicine 13(11):e14495. doi:https://doi.org/10.15252/emmm.202114495
  7. Schneider BG, Peng DF, Camargo MC, Piazuelo MB, Sicinschi LA, Mera R, Romero‐Gallo J, Delgado AG, Bravo LE, Wilson KT (2010) Promoter DNA hypermethylation in gastric biopsies from subjects at high and low risk for gastric cancer. International journal of cancer 127(11):2588-2597. doi:https://doi.org/10.1002/ijc.25274
  8. Sisto M, Ribatti D, Lisi S (2022) E-Cadherin Signaling in Salivary Gland Development and Autoimmunity. Journal of clinical medicine 11(8):2241. doi:https://doi.org/10.3390/jcm11082241
  9. Gerber TS, Ridder DA, Schindeldecker M, Weinmann A, Duret D, Breuhahn K, Galle PR, Schirmacher P, Roth W, Lang H (2022) Constitutive Occurrence of E: N-cadherin Heterodimers in Adherens Junctions of Hepatocytes and Derived Tumors. Cells 11(16):2507. doi:https://doi.org/10.3390/cells11162507
  10. Beavon I (2000) The E-cadherin–catenin complex in tumour metastasis: structure, function and regulation. European journal of cancer 36(13):1607-1620. doi:https://doi.org/10.1016/S0959-8049(00)00158-1
  11. Weigelt B, Reis-Filho JS (2009) Histological and molecular types of breast cancer: is there a unifying taxonomy? Nature reviews Clinical oncology 6(12):718-730. doi:https://doi.org/10.1038/nrclinonc.2009.166
  12. Sahar DE, Behr B, Fong KD, Longaker MT, Quarto N (2010) Unique modulation of cadherin expression pattern during posterior frontal cranial suture development and closure. Cells Tissues Organs 191(5):401-413. doi:https://doi.org/10.1159/000272318
  13. Dhondrup R, Zhang X, Feng X, Lobsang D, Hua Q, Liu J, Cuo Y, Zhuoma S, Duojie G, Duojie Caidan S (2022) Proteomic Analysis Reveals Molecular Differences in the Development of Gastric Cancer. Evidence-Based Complementary and Alternative Medicine 2022:Article ID: 8266544. doi:https://doi.org/10.1155/2022/8266544
  14. Mason EF, Rathmell JC (2011) Cell metabolism: an essential link between cell growth and apoptosis. Biochimica et Biophysica Acta (BBA)-Molecular Cell Research 1813(4):645-654. doi:https://doi.org/10.1016/j.bbamcr.2010.08.011
  15. Jönsson LJ, Alriksson B, Nilvebrant N-O (2013) Bioconversion of lignocellulose: inhibitors and detoxification. Biotechnology for biofuels 6(1):1-10. doi:https://doi.org/10.1186/1754-6834-6-16
  16. Thomas S, Popov VL, Walker DH (2010) Exit mechanisms of the intracellular bacterium Ehrlichia. PloS one 5(12):e15775. doi:https://doi.org/10.1371/journal.pone.0015775
  17. Mirzaei AR, Fazeli F (2022) Bioinformatics analysis of microtubule-associated protein-1 light chain 3 (MAP1LC3A) and (BECN1) genes in autophagy. Cellular, Molecular and Biomedical Reports 2(3):129-137. doi:10.55705/cmbr.2022.345001.1046
  18. Patthey C, Tong YG, Tait CM, Wilson SI (2017) Evolution of the functionally conserved DCC gene in birds. Scientific reports 7(1):1-18. doi:https://doi.org/10.1038/srep42029
  19. Sannigrahi MK, Srinivas CS, Deokate N, Rakshit S (2019) The strong propensity of Cadherin‐23 for aggregation inhibits cell migration. Molecular oncology 13(5):1092-1109. doi:https://doi.org/10.1002/1878-0261.12469
  20. Goto-Silva L, Ayad NM, Herzog IL, Silva NP, Lamien B, Orlande HR, da Costa Souza A, Ribeiro S, Martins M, Domont GB (2019) Computational fluid dynamic analysis of physical forces playing a role in brain organoid cultures in two different multiplex platforms. BMC developmental biology 19(1):1-10. doi:https://doi.org/10.1186/s12861-019-0183-y
  21. Zaka A, Shahzad S, Rao HZ, Hashim Y, Basit S (2021) A novel homozygous frameshift mutation in the DCC gene in a Pakistani family with autosomal recessive horizontal gaze palsy with progressive scoliosis-2 with impaired intellectual development. American Journal of Medical Genetics Part A 185(2):355-361. doi:https://doi.org/10.1002/ajmg.a.61952
  22. Geng YH, Wang ZF, Jia YM, Zheng LY, Chen L, Liu DG, Li XH, Tian XX, Fang WG (2018) Genetic polymorphisms in CDH1 are associated with endometrial carcinoma susceptibility among Chinese Han women. Oncology letters 16(5):6868-6878. doi:https://doi.org/10.3892/ol.2018.9469
  23. Lu X-Q, Zhang J-Q, Zhang S-X, Qiao J, Qiu M-T, Liu X-R, Chen X-X, Gao C, Zhang H-H (2021) Identification of novel hub genes associated with gastric cancer using integrated bioinformatics analysis. BMC cancer 21(1):1-17. doi:https://doi.org/10.1186/s12885-021-08358-7
  24. Machado J, Oliveira C, Carvalho R, Soares P, Berx G, Caldas C, Seruca R, Carneiro F, Sobrinho-Simöes M (2001) E-cadherin gene (CDH1) promoter methylation as the second hit in sporadic diffuse gastric carcinoma. Oncogene 20(12):1525-1528. doi:https://doi.org/10.1038/sj.onc.1204234
  25. Fahed D, Chettab A, Mathe D, Denis M, Traverse-Glehen A, Karlin L, Perrial E, Dumontet C (2022) Netrin-1 expression and targeting in multiple myeloma. Leukemia & Lymphoma 63(2):395-403. doi:https://doi.org/10.1080/10428194.2021.1984459
  26. Ma G, Liu H, Hua Q, Wang M, Du M, Lin Y, Ge Y, Gong W, Zhao Q, Qiang F (2017) KCNMA1 cooperating with PTK2 is a novel tumor suppressor in gastric cancer and is associated with disease outcome. Molecular cancer 16(1):1-10. doi:https://doi.org/10.1186/s12943-017-0613-z
  27. Benusiglio PR, Colas C, Guillerm E, Canard A, Delhomelle H, Warcoin M, Bellanger J, Eyries M, Zizi M, Netter J (2019) Clinical implications of CTNNA1 germline mutations in asymptomatic carriers. Gastric Cancer 22(4):899-903. doi:https://doi.org/10.1007/s10120-018-00907-7