Gene Expression Indicates Altered Immune Modulation and Signaling Pathway Activation in Ovarian Cancer Patients Resistant to Topotecan
Abstract
:1. Introduction
2. Results
2.1. Transcriptomic Database for Biomarker Selection
2.2. Upregulated Genes among Nonresponders Treated with Chemotherapy Excluding Topotecan
2.3. Topotecan-Treated EOC Population
2.4. Upregulated Genes in Topotecan-Treated EOC Population
3. Discussion
4. Methods
4.1. Database Setup
4.2. Clinical Data
4.3. Gene Selecting Algorithm
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Characteristics | All EOC Patients (%) | Topotecan-Treated EOC Patients (%) | ||
---|---|---|---|---|
Stage | ||||
I | 6.7 | 0.9 | ||
II | 4.7 | 2.6 | ||
III | 64.0 | 84.6 | ||
IV | 11.3 | 11.1 | ||
N/A | 13.4 | 0.9 | ||
Grade | ||||
I | 2.6 | 16.2 | ||
II | 17.8 | 80.3 | ||
III | 58.3 | 0.9 | ||
IV | 1.3 | 2.6 | ||
N/A | 20.0 | |||
Subtype | ||||
Serous | 76.9 | 100 | ||
Endometrioid | 3.6 | |||
Clear | 2.2 | |||
N/A | 17.4 | |||
Debulking | ||||
Optimal | 48.5 | 74.4 | ||
Suboptimal | 32.0 | 22.2 | ||
N/A | 19.5 | 3.4 | ||
Progression | (median follow up 16.3 months) | 68.1 | (median follow up 14.8 months) | 88.0 |
Treatment | ||||
Platinum | 87.7 | 100 | ||
Taxol | 49.8 | |||
Combined platinum and taxol | 48.6 | 75.2 | ||
Bevacizumab | 3.5 | 12.8 | ||
Docetaxel | 7.4 | 30.8 | ||
Gemcitabine | 9.1 | 62.4 | ||
Paclitaxel | 15.9 | 25.6 | ||
Topotecan | 8.2 | 100 |
Term | Count | p-Value | Genes | Bonferroni |
---|---|---|---|---|
Extracellular matrix organization | 9 | 3.90 × 10−10 | COL5A1, COL1A1, LOX, POSTN, COL5A2, COL10A1, LUM, SERPINE1, MFAP5 | 1.31 × 10−7 |
Collagen fibril organization | 5 | 3.58 × 10−7 | COL5A1, COL1A1, LOX, COL5A2, LUM | 1.20 × 10−4 |
Skeletal system development | 6 | 1.93 × 10−6 | IGF1, COL1A1, POSTN, COL5A2, COL10A1, AEBP1 | 6.45 × 10−4 |
Cellular response to fibroblast growth factor stimulus | 4 | 1.30 × 10−5 | COL1A1, POSTN, SNAI2, CDC5L | 4.35 × 10−3 |
Collagen catabolic process | 4 | 1.29 × 10−4 | COL5A1, COL1A1, COL5A2, COL10A1 | 4.23 × 10−2 |
PFS Cutoff (Months) | Gene Symbol | Mean Expression (Nonresponder) | Mean Expression (Responder) | Fold Change | Mann–Whitney p-Value | AUC | AUC p-Value |
---|---|---|---|---|---|---|---|
9 | CD200 | 1718.6 | 1165.7 | 1.47 | 2.13 × 10−2 | 0.658 | 8.20 × 10−3 |
12 | EPB41L2 | 1918.2 | 1160.9 | 1.65 | 1.24 × 10−2 | 0.639 | 6.90 × 10−3 |
18 | EPB41L2 | 1703.6 | 1036.1 | 1.64 | 7.70 × 10−3 | 0.648 | 1.80 × 10−3 |
9 | GOLPH3L | 2289.1 | 1583.0 | 1.45 | 2.34 × 10−2 | 0.656 | 6.50 × 10−3 |
12 | HLA-DQA1 | 1353.5 | 908.2 | 1.49 | 1.94 × 10−2 | 0.63 | 8.30 × 10−3 |
9 | HLA-DQB1 | 1243.8 | 830.4 | 1.50 | 2.42 × 10−2 | 0.655 | 8.20 × 10−3 |
12 | HLA-DQB1 | 1202.6 | 737.0 | 1.63 | 4.45 × 10−3 | 0.658 | 1.20 × 10−3 |
15 | LTF | 1034.3 | 316.5 | 3.27 | 4.38 × 10−2 | 0.609 | 1.90 × 10−2 |
18 | LTF | 908.5 | 352.8 | 2.58 | 4.13 × 10−2 | 0.613 | 1.70 × 10−2 |
9 | OVGP1 | 1975.9 | 362.2 | 5.46 | 7.95 × 10−3 | 0.682 | 5.90 × 10−3 |
9 | SCGB2A1 | 11433.0 | 7001.9 | 1.63 | 3.31 × 10−2 | 0.646 | 2.00 × 10−2 |
12 | SFRP1 | 882.5 | 401.5 | 2.20 | 2.46 × 10−2 | 0.625 | 1.20 × 10−2 |
15 | SFRP1 | 727.7 | 393.8 | 1.85 | 1.49 × 10−2 | 0.632 | 5.80 × 10−3 |
18 | SFRP1 | 679.6 | 394.3 | 1.72 | 3.23 × 10−2 | 0.619 | 1.40 × 10−2 |
9 | SLC25A38 | 1838.8 | 1101.3 | 1.67 | 2.55 × 10−2 | 0.707 | 1.90 × 10−4 |
Gene Combinations | AUC Values | p-Values |
---|---|---|
HLA-DQB1 + EPB41L2 | 0.679 | 0.001 |
HLA-DQB1 + SFRP1 | 0.696 | <0.001 |
EPB41L2 + SFRP1 | 0.675 | 0.002 |
HLA-DQB1 + EPB41L2 + SFRP1 | 0.71 | <0.001 |
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Menyhárt, O.; Fekete, J.T.; Győrffy, B. Gene Expression Indicates Altered Immune Modulation and Signaling Pathway Activation in Ovarian Cancer Patients Resistant to Topotecan. Int. J. Mol. Sci. 2019, 20, 2750. https://doi.org/10.3390/ijms20112750
Menyhárt O, Fekete JT, Győrffy B. Gene Expression Indicates Altered Immune Modulation and Signaling Pathway Activation in Ovarian Cancer Patients Resistant to Topotecan. International Journal of Molecular Sciences. 2019; 20(11):2750. https://doi.org/10.3390/ijms20112750
Chicago/Turabian StyleMenyhárt, Otília, János Tibor Fekete, and Balázs Győrffy. 2019. "Gene Expression Indicates Altered Immune Modulation and Signaling Pathway Activation in Ovarian Cancer Patients Resistant to Topotecan" International Journal of Molecular Sciences 20, no. 11: 2750. https://doi.org/10.3390/ijms20112750