Comprehensive Analysis of Gene Expression Profiling to Explore Predictive Markers for Eradication Therapy Efficacy against Helicobacter pylori-Negative Gastric MALT Lymphoma
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Patients
2.2. Evaluation of the API2-MALT1 Chimeric Transcript and Hp Infection
2.3. Therapy Evaluation
2.4. Quantitative Reverse Transcription Polymerase Chain Reaction
2.5. RNA Sequencing
2.6. Analysis Flow
2.7. Statistical Analysis
3. Results
3.1. Patients
3.2. Treatment Outcomes by Eradication Therapy According to API2-MALT1 Chimeric Transcript Status and Hp Infection Status
3.3. Comparison between the CR and NC Groups in Gastric MALT Lymphomas Negative for Both Hp and the API2-MALT1 Chimeric Transcript
3.4. DEGs in Comparison between CR and NC Groups in RNA Sequences
3.5. Transcription Factor Prediction of DEGs
3.6. Protein–Protein Interaction Networks of DEGs
3.7. Pathway Analysis of DEGs
3.8. Predictive Markers for Eradication Therapy against Hp-Negative Gastric MALT Lymphoma
3.9. Real-Time PCR Validation
3.10. Predictability of NANOG and OLFM4
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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CR Group (n = 17) | NC Group (n = 19) | p-Value | ||
---|---|---|---|---|
Median age (range) | 56.4 ± 14.0 (32–79) | 64.9 ± 12.4 (39–88) | 0.063 | |
Sex | Male | 6 (35%) | 7 (37%) | 1 |
Female | 11 (65%) | 12 (63%) | ||
Mucosal atrophy | Closed-type | 14 (82%) | 17 (89%) | 0.650 |
Open-type | 3 (18%) | 2 (11%) | ||
Number of lesions | Single | 5 (29%) | 3 (16%) | 0.434 |
Multiple | 12 (71%) | 16 (84%) | ||
Location | U | 2 (12%) | 3 (16%) | 0.727 |
M/L | 15 (88%) | 16 (84%) | ||
Morphological type | Superficial | 15 (88%) | 17 (90%) | 0.906 † |
Elevated | 0 | 1 (5%) | 0.337 † | |
Other | 2 (12%) | 1 (5%) | 0.481 † |
Detection Method | Gene Symbol | Gene Expression (CR Group) | Gene Expression (NC Group) | Log2 Fold Change | p-Value | FDR | ||
---|---|---|---|---|---|---|---|---|
Upregulated in CR group | Infection-related genes | Based on KEGG pathway analysis | HBA1 | 74,654.784 | 2580.948 | −4.854 | 1.08 × 10−6 * | 0.00106 * |
HBA2 | 113,119.690 | 3758.04 | −4.911 | 7.96 × 10−7 * | 0.000886 * | |||
HBB | 58,139.590 | 2118.052 | −4.778 | 1.76 × 10−6 * | 0.00149 * | |||
HLA-DRB3 | 1826.461 | 139.764 | −3.707 | 0.000142 * | 0.0313 * | |||
Based on DEG | NPIPB3 | 770.699 | 5.639 | −7.094 | 1.40 × 10−15 * | 2.50 × 10−11 * | ||
ALAS2 | 755.955 | 31.467 | −4.586 | 6.15 × 10−6 * | 0.00421 * | |||
OLFM4 | 947.359 | 41.761 | −4.503 | 7.62 × 10−6 * | 0.00468 * | |||
Upregulated in NC group | Cancer-related genes | Based on KEGG pathway analysis | TMEM130 | 71.323 | 561.849 | 2.977 | 0.00014 * | 0.0313 * |
GSTA1 | 50.275 | 600.022 | 3.577 | 7.08 × 10−5 * | 0.0221 * | |||
Based on DEG | LEP | 25.913 | 404.156 | 3.963 | 8.01 × 10−8 * | 0.00013 * | ||
MTRNR2L8 | 25,678.176 | 270,967.1 | 3.399 | 3.87 × 10−8 * | 7.65 × 10−5 * | |||
NANOG | 55.876 | 814.437 | 3.865 | 2.37 × 10−6 * | 0.00191 * | |||
OTUD6A | 64.137 | 977.690 | 3.930 | 1.41 × 10−6 * | 0.00131 * | |||
ZNF669 | 332.030 | 5072 | 3.933 | 3.49 × 10−7 * | 0.000444 * | |||
Transcription factor | ZNF556 | 29.540 | 342.919 | 3.537 | 9.26 × 10−6 * | 0.00549 * | ||
Protein–protein interaction | ACTA1 | 7.572 | 275.414 | 5.184 | 3.75 × 10−8 * | 7.65 × 10−5 * |
Detection Method | Gene Symbol | Gene Expression (CR Group) | Gene Expression (NC Group) | p-Value | FDR | ||
---|---|---|---|---|---|---|---|
Upregulated in CR group | Infection-related genes | Based on KEGG pathway analysis | HBA1 | 1.03 | 0.52 | 0.343 | 0.686 |
HBA2 | 1.47 | 0.40 | 0.236 | 0.629 | |||
HBB | 2.91 | 1.66 | 0.564 | 0.752 | |||
HLA-DRB3 | 0.00 | 0.01 | 0.6 | 0.738 | |||
Based on DEG | NPIPB3 | 0.11 | 0.04 | 0.033 * | 0.132 | ||
ALAS2 | 0.06 | 0.00 | 0.112 | 0.358 | |||
OLFM4 | 1.84 | 0.32 | 0.005 * | 0.04 * | |||
Upregulated in NC group | Cancer-related genes | Based on KEGG pathway analysis | TMEM130 | 0.82 | 0.72 | 0.887 | 0.887 |
GSTA1 | 1.95 | 2.57 | 0.785 | 0.837 | |||
Based on DEG | LEP | 0.23 | 0.28 | 0.382 | 0.611 | ||
MTRNR2L8 | 0.67 | 0.60 | 0.768 | 0.878 | |||
NANOG | 1.36 | 6.11 | 0.003 * | 0.048 * | |||
OTUD6A | 0.20 | 0.27 | 0.286 | 0.654 | |||
ZNF669 | 0.28 | 0.98 | 0.365 | 0.649 | |||
Transcription factor | ZNF556 | 0.26 | 0.52 | 0.018 * | 0.096 | ||
Protein–protein interaction | ACTA1 | 0.25 | 0.67 | 0.383 | 0.557 |
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Takigawa, H.; Yuge, R.; Miyamoto, R.; Otani, R.; Kadota, H.; Hiyama, Y.; Hayashi, R.; Urabe, Y.; Sentani, K.; Oue, N.; et al. Comprehensive Analysis of Gene Expression Profiling to Explore Predictive Markers for Eradication Therapy Efficacy against Helicobacter pylori-Negative Gastric MALT Lymphoma. Cancers 2023, 15, 1206. https://doi.org/10.3390/cancers15041206
Takigawa H, Yuge R, Miyamoto R, Otani R, Kadota H, Hiyama Y, Hayashi R, Urabe Y, Sentani K, Oue N, et al. Comprehensive Analysis of Gene Expression Profiling to Explore Predictive Markers for Eradication Therapy Efficacy against Helicobacter pylori-Negative Gastric MALT Lymphoma. Cancers. 2023; 15(4):1206. https://doi.org/10.3390/cancers15041206
Chicago/Turabian StyleTakigawa, Hidehiko, Ryo Yuge, Ryo Miyamoto, Rina Otani, Hiroki Kadota, Yuichi Hiyama, Ryohei Hayashi, Yuji Urabe, Kazuhiro Sentani, Naohide Oue, and et al. 2023. "Comprehensive Analysis of Gene Expression Profiling to Explore Predictive Markers for Eradication Therapy Efficacy against Helicobacter pylori-Negative Gastric MALT Lymphoma" Cancers 15, no. 4: 1206. https://doi.org/10.3390/cancers15041206
APA StyleTakigawa, H., Yuge, R., Miyamoto, R., Otani, R., Kadota, H., Hiyama, Y., Hayashi, R., Urabe, Y., Sentani, K., Oue, N., Kitadai, Y., Oka, S., & Tanaka, S. (2023). Comprehensive Analysis of Gene Expression Profiling to Explore Predictive Markers for Eradication Therapy Efficacy against Helicobacter pylori-Negative Gastric MALT Lymphoma. Cancers, 15(4), 1206. https://doi.org/10.3390/cancers15041206