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
Indian Journal of Surgical Oncology
Published in: Indian Journal of Surgical Oncology 1/2021

01-04-2021 | Gastric Cancer | Original Article

mRNA Expression Analysis of E-Cadherin, VEGF, and MMPs in Gastric Cancer: a Pilot Study

Authors: Puneet Kumar, Arun Sebastian, Khushi Verma, Ruhi Dixit, Soni Kumari, Juhi Singh, Satyendra Kumar Tiwary, Gopeshwar Narayan

Published in: Indian Journal of Surgical Oncology | Special Issue 1/2021

Login to get access

Abstract

Gastric cancer (GC) is a serious fatal cancer on a global scale because of its presentation at advanced stage. The expressions of vascular endothelial growth factor (VEGF), E-cadherin, and matrix metalloproteinases (MMPs) in other cancers have been reported. However, its expression and underlying mechanisms are little known in gastric cancer in Indian context. In this study, we detected mRNA expression of VEGF, E-cadherin, and MMPs (MMP-1, MMP-2, and MMP-9) in 73 gastric cancer tissues and 27 normal controls by reverse-transcriptase polymerase chain reaction (RT-PCR). Receiver operator characteristics analysis was done for determining the diagnostic utility of VEGF, MMPs and E-cadherin with respect to the sensitivity and specificity. The association of VEGF, MMPs, and E-cadherin expression with the clinicopathological characteristics and the prognosis was subsequently analyzed. The mRNA expression results showed that E-cadherin was significantly downregulated in 47.9% of GC in comparison to control. There was no change in VEGF expression observed in 90.4% GC cases. MMP-1, MMP-2, and MMP-9 were overexpressed in 13.7%, 28.8%, and 11% of GC, respectively, with significant change in MMP-2 (p ≤ 0.0001) and MMP-9 (p = 0.027) in comparison to control. Our results strengthen the necessity of more studies to elucidate the prophetic role of these genes in the development of gastric cancer.
Literature
1.
2.
Karimi P, Islami F, Anandasabapathy S, Freedman ND, Kamangar F (2014) Gastric cancer: descriptive epidemiology, Risk Factors, Screening, and Prevention. Cancer Epidemiol Biomarkers Prev 23(5):700–713CrossRef
3.
Murugesan CS, Manickavasagam K, Chandramohan A, Jebaraj A, Jameel ARA, Jain MS, Venkataraman J (2018) Gastric cancer in India: epidemiology and standard of treatment. Updat Surg 70:233–239CrossRef
4.
Howlader N, Noone AM, Krapcho M, Neyman N, Aminou R, Waldron W, Altekruse SF, Kosary CL, Ruhl J, Tatalovich Z, Cho H, Mariotto A, Eisner MP, Lewis DR, Chen HS, Feuer EJ, Cronin KA, Edwards BK (2011) SEER cancer statistics review, 1975-2008. National Cancer Institute, Bethesda Based on November 2010 SEER data submission, Posted to the SEER Web Site
5.
Quail DF, Joyce JA (2013) Microenvironmental regulation of tumor progression and metastasis. Nat Med 19(11):1423–1437CrossRef
6.
Hicklin DJ, Ellis LM (2005) Role of the vascular endothelial growth factor pathway in tumor growth and angiogenesis. J Clin Oncol 23:1011–1027CrossRef
7.
Maeda K, Chung YS, Ogawa Y, Takatsuka S, Kang SM, Ogawa M, Sawada T, Sowa M (1996) Prognostic value of vascular endothelial growth factor expression in gastric carcinoma. Cancer. 77:858–863CrossRef
8.
Shiozaki H, Oka H, Inoue M, Tamura S, Monden M (1996) E-cadherin mediated adhesion system in cancer cells. Cancer 77:1605–1613CrossRef
9.
Wong SHM, Fang CM, Chuah LH, Leong CO, Ngai SC (2018) E-cadherin: its dysregulation in carcinogenesis and clinical implications. Crit Rev Oncol Hematol 121:11–22CrossRef
10.
Zhou Y, Li G, Wu J, Zhang Z, Wu Z, Fan P, Hao T, Zhang X, Li M, Zhang F, Li Q, Lu B, Qiao L (2010) Clinicopathological significance of E-cadherin, VEGF, and MMPs in gastric cancer. Tumour Biol 31(6):549–558CrossRef
11.
12.
Kubben FJGM, Sier CFM, van Duijn W, Griffioen G, Hanemaaijer R, van de Velde CJ, van Krieken JH, Lamers CB, Verspaget HW (2006) Matrix metalloproteinase-2 is a consistent prognostic factor in gastric cancer. Br J Cancer 94:1035–1040CrossRef
13.
Kahari VM, Saarialho-Kere U (1999) Matrix metalloproteinases and their inhibitors in tumour growth and invasion. Ann Med 31:34–45CrossRef
14.
Shin DH, Dier U, Melendez JA, Hempel N (2015) Regulation of MMP-1 expression in response to hypoxia is dependent on the intracellular redox status of metastatic bladder cancer cells. Biochim Biophys Acta 1852:2593–2602CrossRef
15.
16.
Cai QW, Li J, Li XQ, Wang JQ, Huang Y (2012) Expression of STAT3, MMP-1 and TIMP-1 in gastric cancer and correlation with pathological features. Mol Med Rep 5:1438–1442PubMed
17.
Kumar V, Abbas A, Fausto N, Robbins C (2010) Pathologic basis of disease, 8th edn. Elsevier Printed in China, Copyright, pp 62–63 82, 206–209,302–303, 328–331
18.
Crew KD, Neugut AI (2006) Epidemiology of gastric cancer. World J Gastroenterol 12(3):354–362CrossRef
19.
Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun MJ (2009) Cancer statistics, 2009. CA Cancer J Clin 59(4):225–249CrossRef
20.
Shibuya M (2015) VEGF-VEGFR system as a target for suppressing inflammation and other diseases. Endocr Metab Immune Disord Drug Targets 15(2):135–144CrossRef
21.
Park SH, Lee SS (2003) The relationship between serum VEGF concentration and prognosis of lung cancer. Korean J Intern Med 18(4):207–211CrossRef
22.
Schizas D, Moris D, Michalinos A, Kanavidis P, Oikonomou D, Papalampros A, Machairas A, Liakakos T (2017) E-cadherin in gastric carcinomas: relations with histological parameters and its prognostic value. J BUON 22(2):383–389PubMed
23.
Czyzewska J, Guzinska-Ustymowicz K, Ustymowicz M, Pryczynicz A, Kemona A (2010) The expression of E-cadherin- catenin complex in patients with advanced gastric cancer: role in formation of metastasis. Folia Histochem Cytobiol 48:37–45CrossRef
24.
Stanculescu D, Margaritescu C, Stepan A, Mitrut AO (2011) E-cadherin in gastric carcinomas related to histological prognostic parameters. Romanian J Morphol Embryol 52(3 Suppl):1107–1112
25.
Zhou YN, Xu CP, Han B, Li M, Qiao L, Fang DC, Yang JM (2002) Expression of E-cadherin and beta-catenin in gastric carcinoma and its correlation with the clinicopathological features and patient survival. World J Gastroenterol 8:987–993CrossRef
26.
Chan AO, Lam SK, Wong BC, Wong WM, Yuen MF, Yeung YH, Hui WM, Rashid A, Kwong YL (2003) Promoter methylation of E-cadherin gene in gastric mucosa associated with helicobacter pylori infection and in gastric cancer. Gut 52:502–506CrossRef
27.
Guzman P, Araya J, Villaseca M, Roa I, Melo A, Muñoz S, Roa J (2006) Immunohistochemical expression of the E-cadherin-catenin complex in gastric cancer. Rev Med Chil 134:1002–1009 (Abstract)CrossRef
28.
Jeanes A, Gottardi CJ, Yap AS (2008) Cadherins and cancer: how does cadherin dysfunction promote tumor progression? Oncogene 27:6920–6929CrossRef
29.
Anbiaee R, Mojir Sheibani K, Torbati P, Jaam H (2013) Abnormal expression of e-cadherin in gastric adenocarcinoma, and its correlation with tumor histopathology and helicobacter pylori infection. Iran Red Crescent Med J 15:218–222CrossRef
30.
Karayiannakis AJ, Syrigos KN, Chatzigianni E, Papanikolaou S, Karatzas G (1998) E-cadherin expression as a differentiation marker in gastric cancer. Hepatogastroenterology 45:2437–2442PubMed
31.
Ohno T, Aihara R, Kamiyama Y, Mochiki E, Asao T, Kuwano H (2006) Prognostic significance of combined expression of MUC1 and adhesion molecules in advanced gastric cancer. Eur J Cancer 42:256–263CrossRef
32.
Lee MY, Chou CY, Tang MJ, Shen MR (2008) Epithelial–mesenchymal transition in cervical cancer: correlation with tumor progression, epidermal growth factor receptor overexpression, and snail upregulation. Clin Cancer Res 14:4743–4750CrossRef
33.
Hauff SJ, Raju SC, Orosco RK, Gross AM, Diaz-Perez JA, Savariar E, Nashi N, Hasselman J, Whitney M, Myers JN, Lippman SM, Tsien RY, Ideker T, Nguyen QT (2014) Matrix-metalloproteinases in head and neck carcinoma-cancer genome atlas analysis and fluorescence imaging in mice. Otolaryngol Head Neck Surg 151(4):612–618CrossRef
34.
Liu LQ, Chen ZW, Yi SJ (2018) association between the expression of MMP1 gene and prognosis in head and neck squamous cell carcinoma. Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi 32(4):287–291 (Abstract)PubMed
35.
Boström P, Soderstrom M, Vahlberg T, Soderstrom KO, Roberts PJ, Carpen O, Hirsimäki P (2011) MMP-1 expression has an independent prognostic value in breast cancer. BMC Cancer 11:348CrossRef
36.
37.
38.
Kuo HY, Huang YS, Tseng CH, Chen YC, Chang YW, Shih HM, Wu CW (2014) PML represses lung cancer metastasis by suppressing the nuclear EGFR-mediated transcriptional activation of MMP2. Cell Cycle 13:3132–3142CrossRef
39.
Yu Y, Ding Z, Jian H, Shen L, Zhu L, Lu S (2016) Prognostic value of MMP9 activity level in resected stage I B lung adenocarcinoma. Cancer Med 5:2323–2331CrossRef
40.
De Mingo M, Moran A, Sanchez-Pernaute A, Iniesta P, Diez-Valladares L, Perez-Aguirre E, de Juan C, García-Aranda C, Díaz-López A, García-Botella A, Martín-Antona E, Benito M, Torres A, Balibrea JL (2007) Expression of MMP-9 and TIMP-1 as prognostic markers in gastric carcinoma. Hepatogastroenterology 54:315–319PubMed
41.
Elnemr A, Yonemura Y, Bandou E, Kinoshita K, Kawamura T, Takahashi S, Tochiori S, Endou Y, Sasaki T (2003) Expression of collagenase-3 (matrix metalloproteinase-13) in human gastric cancer. Gastric Cancer 6:30–38CrossRef
42.
Sier CF, Kubben FJ, Ganesh S, Heerding MM, Griffioen G, Hanemaaijer R, van Krieken JH, Lamers CB, Verspaget HW (1996) Tissue levels of matrix metalloproteinases MMP-2 and MMP-9 are related to the overall survival of patients with gastric carcinoma. Br J Cancer 74:413–417CrossRef
43.
Sunami E, Tsuno N, Osada T, Saito S, Kitayama J, Tomozawa S, Tsuruo T, Shibata Y, Muto T, Nagawa H (2000) MMP-1 is a prognostic marker for hematogenous metastasis of colorectal cancer. Oncologist. 5(2):108–114CrossRef
44.
Gao H, Lan X, Li S, Xue Y (2017) Relationships of MMP-9, E-cadherin, and VEGF expression with clinicopathological features and response to chemosensitivity in gastric cancer. Tumour Biol 39(5):1010428317698368CrossRef
45.
Zheng H, Takahashi H, Murai Y, Cui Z, Nomoto K, Niwa H, Tsuneyama K, Takano Y (2006) Expressions of MMP-2, MMP-9 and VEGF are closely linked to growth, invasion, metastasis and angiogenesis of gastric carcinoma. Anticancer Res 26(5A):3579–3583PubMed
46.
Guo CB, Wang S, Deng C, Zhang DL, Wang FL, Jin XQ (2007) Relationship between matrix metalloproteinase 2 and lung cancer progression. Mol Diagn Ther 11(3):183–192CrossRef
Metadata
Title
mRNA Expression Analysis of E-Cadherin, VEGF, and MMPs in Gastric Cancer: a Pilot Study
Authors
Puneet Kumar
Arun Sebastian
Khushi Verma
Ruhi Dixit
Soni Kumari
Juhi Singh
Satyendra Kumar Tiwary
Gopeshwar Narayan
Publication date
01-04-2021
Publisher
Springer India
Published in
Indian Journal of Surgical Oncology / Issue Special Issue 1/2021
Print ISSN: 0975-7651
Electronic ISSN: 0976-6952
DOI
https://doi.org/10.1007/s13193-020-01096-5

Other articles of this Special Issue 1/2021

Indian Journal of Surgical Oncology 1/2021 Go to the issue

Original Article

TRF2 Overexpression at the Surgical Resection Margin: A Potential Predictive Biomarker in Oral Squamous Cell Carcinoma for Recurrence

Original Article

Role of CAIX Expression in Conventional Renal Cell Carcinomas as a Diagnostic Marker and its Prognostic Importance

Original Article

Analysis of SET and MYND Domain-Containing Protein 3 (SMYD3) Expression in Gallbladder Cancer: a Pilot Study

Original Article

Clinical and Histopathological Correlation of p16 and p53 Expression in Oral Cancer

Review Article

microRNAs: New-Age Panacea in Cancer Therapeutics

Review Article

Pancreatic Cancer Immuno-oncology in the Era of Precision Medicine