Association of Microsatellite Instability and Gene Expression Profile in Colorectal Carcinoma and Potential Implications for Therapy
Abstract
:1. Introduction
2. Materials and Methods
2.1. Genome-Wide Gene Expression Assay
2.2. MSI Detection
2.3. Statistical Analysis
3. Results
3.1. Gene-Level Analysis
3.2. Enrichment Analysis of Differentially Expressed Genes
3.3. Gene-Set or Pathway Level Analysis
3.4. Differential Gene Expression: MSI vs. MSS Tumors
3.5. Previously Reported Genes in Our Data Set
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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Characteristic | Category | MSI | MSS | Chi Square p-Value |
---|---|---|---|---|
Sex | Male | 4 | 24 | 0.14 |
Female | 14 | 29 | ||
Location | Distal | 11 | 47 | 0.023 |
Proximal | 7 | 6 | ||
Stage | Stage-1 | 3 | 9 | 0.68 |
Stage-2 | 7 | 15 | ||
Stage-3 | 8 | 29 | ||
Tumor Grade | Low | 14 | 43 | 1 |
High | 4 | 10 | ||
LymphNode | Present | 8 | 29 | 0.63 |
Absent | 10 | 24 | ||
TIL | 0 | 12 | 27 | 0.37 |
1 | 6 | 26 | ||
Signet ring | Absent | 14 | 37 | 0.72 |
Present | 4 | 16 | ||
LVinvasion | Absent | 12 | 24 | 0.19 |
Present | 6 | 29 | ||
PNinvasion | Absent | 15 | 40 | 0.72 |
Present | 3 | 13 | ||
KRAS | Mutant | 5 | 15 | 0.79 |
Wild | 13 | 38 | ||
BRAF | Mutant | 1 | 0 | 0.56 |
Wild | 17 | 53 |
MSI | MSS | ||||||
---|---|---|---|---|---|---|---|
Gene Sets | Interaction | Fold Change | (95% CI) | p | Fold Change | (95% CI) | p |
p | |||||||
IL-17 signaling pathway | 0.000957916 | 1.19 | (1.16–1.21) | 1.02 × 10−59 | 1.15 | (1.13–1.16) | 8.11 × 10−104 |
Retinol metabolism | 0.000177561 | −1.27 | (−1.31–1.23) | 7.35 × 10−56 | −1.20 | (−1.21–1.17) | 1.19368 × 10−86 |
Chemical carcinogenesis | 6.15 × 10−5 | −1.18 | (−1.21–1.15) | 1.11 × 10−48 | −1.15 | (−1.16–1.13) | 1.66064 × 10−90 |
Drug metabolism—cytochrome P450 | 0.000231622 | −1.22 | (−1.25–1.18) | 5.92 × 10−43 | −1.17 | (−1.19–1.15) | 1.74586 × 10−76 |
Intestinal immune network for IgA production | 2.37 × 10−8 | −1.15 | (−1.18–1.10) | 9.73 × 10−16 | −1.29 | (−1.31–1.26) | 7.7175 × 10−132 |
Steroid hormone biosynthesis | 0.000179774 | −1.22 | (−1.25–1.18) | 1.01 × 10−41 | −1.14 | (−1.16–1.12) | 6.24018 × 10−53 |
Pentose and glucuronate interconversions | 3.37 × 10−6 | −1.35 | (−1.40–1.28) | 2.24 × 10−40 | −1.23 | (−1.26–1.19) | 1.17089 × 10−54 |
Metabolism of xenobiotics by cytochrome P450 | 0.000177715 | −1.17 | (−1.20–1.14) | 3.48 × 10−32 | −1.14 | (−1.15–1.11) | 1.60731 × 10−56 |
Vascular smooth muscle contraction | 2.30 × 10−6 | −1.07 | (−1.08–1.05) | 2.87 × 10−27 | −1.06 | (−1.06–1.05) | 3.17997 × 10−54 |
Ether lipid metabolism | 0.591294 | −1.13 | (−1.15–1.10) | 6.57 × 10−23 | −1.11 | (−1.12–1.09) | 1.49968 × 10−47 |
Ascorbate and aldarate metabolism | 8.54 × 10−7 | −1.29 | (−1.35–1.23) | 1.31 × 10−26 | −1.20 | (−1.22–1.16) | 1.9392 × 10−35 |
Porphyrin and chlorophyll metabolism | 4.22 × 10−5 | −1.17 | (−1.20–1.13) | 3.23 × 10−22 | −1.12 | (−1.14–1.10) | 2.08756 × 10−33 |
Salmonella infection | 3.63 × 10−7 | 1.11 | (1.08–1.12) | 8.10 × 10−25 | 1.06 | (1.04–1.07) | 1.21337 × 10−24 |
Protein digestion and absorption | 0.0136228 | 1.08 | (1.05–1.09) | 1.34 × 10−15 | 1.08 | (1.06–1.09) | 9.45574 × 10−42 |
Amoebiasis | 0.0187527 | 1.09 | (1.07–1.11) | 4.57 × 10−19 | 1.06 | (1.04–1.06) | 1.29366 × 10−21 |
Drug metabolism—other enzymes | 2.02 × 10−8 | −1.11 | (−1.13–1.08) | 3.14 × 10−18 | −1.06 | (−1.07–1.04) | 3.68932 × 10−19 |
Legionellosis | 8.09 × 10−8 | 1.11 | (1.07–1.13) | 9.76 × 10−17 | 1.06 | (1.04–1.07) | 1.91509 × 10−16 |
Malaria | 0.000186005 | 1.18 | (1.13–1.21) | 1.12 × 10−18 | 1.08 | (1.05–1.10) | 8.28788 × 10−12 |
Biosynthesis of amino acids | 3.22 × 10−12 | 1.06 | (1.03–1.07) | 2.82 × 10−10 | 1.05 | (1.04–1.06) | 1.95178 × 10−24 |
TNF signaling pathway | 1.67 × 10−6 | 1.06 | (1.04–1.07) | 3.71 × 10−18 | 1.03 | (1.01–1.03) | 2.34661 × 10−9 |
Rheumatoid arthritis | 4.08 × 10−17 | 1.15 | (1.12–1.17) | 2.39 × 10−26 | 1.02 | (1.00–1.03) | 0.0193784 |
Epithelial cell signaling in Helicobacter pylori infection | 0.52238 | 1.05 | (1.03–1.07) | 1.18 × 10−8 | 1.04 | (1.03–1.05) | 1.09674 × 10−13 |
Vitamin B6 metabolism | 0.00322795 | 1.14 | (1.05–1.21) | 0.000387 | 1.12 | (1.07–1.16) | 7.67061 × 10−8 |
Arachidonic acid metabolism | 0.059206 | −1.02 | (−1.04–1.00) | 0.0502923 | −1.02 | (−1.03–1.01) | 0.000402162 |
Viral protein interaction with cytokine and cytokine receptor | 2.43 × 10−9 | 1.02 | (−1.00–1.03) | 0.120965 | −1.06 | (−1.06–1.04) | 6.93335 × 10−18 |
NF-kappa B signaling pathway | 9.57 × 10−7 | 1.02 | (1.00–1.03) | 0.0397081 | −1.03 | (−1.04–1.02) | 1.01891 × 10−11 |
African trypanosomiasis | 0.0268193 | 1.04 | (1.00–1.07) | 0.0214121 | −1.01 | (−1.03–1.00) | 0.171386 |
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Kibriya, M.G.; Jasmine, F.; Khamkevych, Y.; Raza, M.; Kamal, M.; Bissonnette, M.; Ahsan, H. Association of Microsatellite Instability and Gene Expression Profile in Colorectal Carcinoma and Potential Implications for Therapy. Medicina 2024, 60, 348. https://doi.org/10.3390/medicina60030348
Kibriya MG, Jasmine F, Khamkevych Y, Raza M, Kamal M, Bissonnette M, Ahsan H. Association of Microsatellite Instability and Gene Expression Profile in Colorectal Carcinoma and Potential Implications for Therapy. Medicina. 2024; 60(3):348. https://doi.org/10.3390/medicina60030348
Chicago/Turabian StyleKibriya, Muhammad G., Farzana Jasmine, Yuliia Khamkevych, Maruf Raza, Mohammed Kamal, Marc Bissonnette, and Habibul Ahsan. 2024. "Association of Microsatellite Instability and Gene Expression Profile in Colorectal Carcinoma and Potential Implications for Therapy" Medicina 60, no. 3: 348. https://doi.org/10.3390/medicina60030348