Overview of Gene Expression Analysis in Gastric Disease Infected with Helicobacter pylori: CLDN1 and MMP9 Could Be Biomarkers for Early Diagnosis of Gastric Cancer
Abstract
:1. Introduction
2. Materials and Methods
2.1. Ethical Approval and Consent to Participate
2.2. Gastric Biopsy Samples
2.3. RNA Isolation and Expression Microarray Analysis
2.4. Microarray Assays
2.5. Microarray Analysis and Selection of Differentially Expressed Genes
2.6. Enriched Gene Ontology Terms
2.7. Amplification of Gene Expression by qPCR
2.8. Validation of Gene Assays
2.9. Immunohistochemistry of CLDN1 and MMP9
2.10. Statistical Analysis
3. Results
3.1. Clinical Characteristics of Enrolled Patients
3.2. Differential Expression of Genes between the Study Groups
3.3. Differential Expression of Genes between Chronic Atrophic Gastritis and Gastric Cancer
3.4. Differential Expression of Genes between Chronic Atrophic Gastritis and the Control
3.5. Significant Molecular Differences between Gastric Cancer and the Control Group
3.6. Biological Difference between Gastric Cancer and Chronic Atrophic Gastritis
3.7. Changes in Gene Expression in Chronic Atrophic Gastritis Tissue May Be Involved in Carcinogenesis
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Clinical Entity | N | Age * | Gender | Pathological Diagnosis |
---|---|---|---|---|
Follicular gastritis (control group) | 7 | 45 ± 3.6 | M | Chronic follicular gastritis demonstrating activity associated with H. pylori and scarce bacilli in the body and antrum |
F | Chronic follicular gastritis with a moderate activity associated with H. pylori in the antral mucosa | |||
M | Chronic follicular gastritis with moderate activity in the antrum and body, associated with moderate bacilli H. pylori | |||
F | Chronic follicular gastritis with a moderate activity associated with H. pylori and a moderate amount in the antrum | |||
F | Chronic follicular gastritis with a moderate activity associated with H. pylori and scarce bacilli in the antrum and body | |||
F | Chronic follicular gastritis moderate with a moderate activity associated with H. pylori in the mucous membrane of the antrum | |||
F | Chronic follicular gastritis with a mild activity associated with H. pylori and scarce bacilli in the antrum and body | |||
Chronic atrophic gastritis | 3 | 67 ± 1.76 | F | Chronic atrophic gastritis with an intense activity associated in the antrum |
F | Chronic atrophic gastritis with complete intestinal metaplasia | |||
F | Chronic atrophic gastritis with a mild activity associated with complete intestinal metaplasia in the antral mucosa and chronic follicular gastritis with a mild activity associated with complete intestinal metaplasia in the oxyntic mucosa | |||
Gastric cancer | 3 | 59 ± 10.07 | F | Gastric adenocarcinoma of intestinal type well differentiated in the antrum. There is no residual mucosa, so immunohistochemistry will not be performed |
F | Gastric adenocarcinoma of the intestinal type with mucinous areas | |||
F | Gastric adenocarcinoma of the intestinal type |
KEGG Pathway | Genes | % | Enrichment | p-Value | Benjamini |
---|---|---|---|---|---|
Drug metabolism | 6 | 2.79 | 10.4343 | 0.0002 | 0.0203 |
Caffeine metabolism | 3 | 1.40 | 32.0483 | 0.0034 | 0.1467 |
Arginine and proline metabolism | 5 | 2.33 | 7.0547 | 0.0050 | 0.1416 |
PPAR signaling pathway | 5 | 2.33 | 5.4188 | 0.0125 | 0.2517 |
Histidine metabolism | 3 | 1.40 | 7.7358 | 0.0553 | 0.6487 |
Alanine, aspartate, and glutamate metabolism | 3 | 1.40 | 7.2367 | 0.0623 | 0.6268 |
KEGG Pathway | Genes | % | Enrichment | p-Value | Benjamini |
---|---|---|---|---|---|
Arrhythmogenic right ventricular cardiomyopathy | 10 | 2.02 | 4.3447 | 0.0004 | 0.0568 |
Arginine and proline metabolism | 8 | 1.62 | 4.9841 | 0.0009 | 0.0653 |
Nitrogen metabolism | 5 | 1.01 | 7.1781 | 0.0045 | 0.1933 |
Tight junction | 11 | 2.22 | 2.7106 | 0.0067 | 0.2163 |
Leukocyte transendothelial migration | 10 | 2.02 | 2.7983 | 0.0087 | 0.2230 |
Histidine metabolism | 5 | 1.01 | 5.6930 | 0.0104 | 0.2222 |
Maturity onset diabetes of the young | 4 | 0.81 | 5.2831 | 0.0378 | 0.5477 |
Glycerolipid metabolism | 5 | 1.01 | 3.6688 | 0.0452 | 0.5652 |
P53 signaling pathway | 6 | 1.21 | 2.9135 | 0.0529 | 0.5754 |
Dilated cardiomyopathy | 7 | 1.41 | 2.5124 | 0.0578 | 0.5754 |
Focal adhesion | 11 | 2.22 | 1.8070 | 0.0799 | 0.6638 |
KEGG Pathway | Genes | % | Enrichment | p-Value | Benjamini |
---|---|---|---|---|---|
Linoleic acid metabolism | 2 | 4.35 | 25.9439 | 0.0693 | 0.7942 |
Fructose and mannose metabolism | 2 | 4.35 | 21.3655 | 0.0836 | 0.6173 |
Genes | Microarray Fold Change | qPCR 2−ΔΔCt | ||||
---|---|---|---|---|---|---|
CAG | GC | GC vs. CAG | CAG | GC | GC vs. CAG | |
Claudin-1 | 3.42 | 6.04 | 4.62 | 0.51 | 0.06 | 0.12 |
Claudin-7 | 5.89 | 6.62 | 2.72 | 0.03 | 0.01 | 0.45 |
MYC | 2.50 | 3.43 | 2.93 | 2.46 | 1.11 | 0.45 |
Matrix metalloproteinase-9 | 1.55 | 2.68 | 3.13 | 7.79 | 3.40 | 0.44 |
Olfactomedin-4 | 8.02 | 7.75 | 1.73 | 0.05 | 0.003 | 0.06 |
Clinical Entity | N | Age * | Gender | Pathological Diagnosis | |
---|---|---|---|---|---|
F | M | ||||
Gastric biopsy without alterations | 18 | 49 ± 4.58 | 13 | 5 | Gastric biopsy without significant histological alterations in antral or oxyntic mucosa |
Follicular gastritis | 20 | 56 ± 3.73 | 14 | 6 | Chronic follicular gastritis with a mild or moderate activity, associated with H. pylori infection in the antrum, body, or oxyntic mucosa |
Chronic atrophic gastritis | 20 | 68 ± 2.80 | 12 | 8 | Non-metaplastic chronic atrophic gastritis in the fund, antrum, or body |
Gastric cancer | 24 | 60 ± 3.56 | 10 | 14 | Moderately—poorly differentiated adenocarcinoma intestinal type (13) |
Moderately—poorly differentiated, invasive and ulcerated intestinal type adenocarcinoma (6) | |||||
Gastric adenocarcinoma of the intestinal type (1) | |||||
Well-differentiated intestinal adenocarcinoma (1) | |||||
Intestinal adenocarcinoma with papillary pattern (1) | |||||
Moderately differentiated, ulcerated intestinal adenocarcinoma (T3). Gastric Resection (3) | |||||
Positive control CLDN1 | 1 | 75 | F | Right colon biopsy | |
Positive control MMP9 | 1 | 40 | M | Liver explant |
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Rivas-Ortiz, C.I.; Morales-Guerrero, S.E.; Ponce-de-León-Rosales, S.; Gamboa-Domínguez, A.; Rangel-Escareño, C.; Uscanga-Domínguez, L.F.; Aguilar-Gutiérrez, G.R.; Kershenobich-Stalnikowitz, D.; López-Vidal, Y.; Castillo-Rojas, G. Overview of Gene Expression Analysis in Gastric Disease Infected with Helicobacter pylori: CLDN1 and MMP9 Could Be Biomarkers for Early Diagnosis of Gastric Cancer. Processes 2022, 10, 196. https://doi.org/10.3390/pr10020196
Rivas-Ortiz CI, Morales-Guerrero SE, Ponce-de-León-Rosales S, Gamboa-Domínguez A, Rangel-Escareño C, Uscanga-Domínguez LF, Aguilar-Gutiérrez GR, Kershenobich-Stalnikowitz D, López-Vidal Y, Castillo-Rojas G. Overview of Gene Expression Analysis in Gastric Disease Infected with Helicobacter pylori: CLDN1 and MMP9 Could Be Biomarkers for Early Diagnosis of Gastric Cancer. Processes. 2022; 10(2):196. https://doi.org/10.3390/pr10020196
Chicago/Turabian StyleRivas-Ortiz, Claudia Ivette, Stephanie Euridice Morales-Guerrero, Sergio Ponce-de-León-Rosales, Armando Gamboa-Domínguez, Claudia Rangel-Escareño, Luis Federico Uscanga-Domínguez, Germán Rubén Aguilar-Gutiérrez, David Kershenobich-Stalnikowitz, Yolanda López-Vidal, and Gonzalo Castillo-Rojas. 2022. "Overview of Gene Expression Analysis in Gastric Disease Infected with Helicobacter pylori: CLDN1 and MMP9 Could Be Biomarkers for Early Diagnosis of Gastric Cancer" Processes 10, no. 2: 196. https://doi.org/10.3390/pr10020196
APA StyleRivas-Ortiz, C. I., Morales-Guerrero, S. E., Ponce-de-León-Rosales, S., Gamboa-Domínguez, A., Rangel-Escareño, C., Uscanga-Domínguez, L. F., Aguilar-Gutiérrez, G. R., Kershenobich-Stalnikowitz, D., López-Vidal, Y., & Castillo-Rojas, G. (2022). Overview of Gene Expression Analysis in Gastric Disease Infected with Helicobacter pylori: CLDN1 and MMP9 Could Be Biomarkers for Early Diagnosis of Gastric Cancer. Processes, 10(2), 196. https://doi.org/10.3390/pr10020196