Identification of Factors Driving Doxorubicin-Resistant Ewing Tumor Cells to Survival
Abstract
Simple Summary
Abstract
1. Background
2. Materials and Methods
2.1. Materials
2.2. Primary Tissue Samples
2.3. Cell Cultures
2.4. cDNA Library Preparation and Single-Cell RNA-Seq
2.5. Proteomic Data Generation and Analysis
2.6. Data Source, Data Processing, and Data Distribution
2.7. Functional GO Enrichment Analysis
2.8. Experimental Validation of Fold-Change Values Using Semiquantitative RT-PCR Analysis
2.9. Statistical Analyses
2.10. Availability of Data and Materials
3. Results
3.1. Hypoxia and Metastatic Traits Distinguish Tumor Cells from Non-Neoplastic Cells
3.2. Embryonic Fibroblasts (M19) and ES (ES36) Cells Are Genetically Close
3.3. Proteomic Profiling of DOX-Treated ES36 Cells Provides a Unique Signature
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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Univariate | Multivariate | |||||
---|---|---|---|---|---|---|
Beta | HR (95% CI) | p.Value | Beta | HR (95% CI) | p.Value | |
Sex | −0.47 | 0.62 (0.21–1.9) | 0.4 | −2.358 | 0.095 (0.005–1.84) | 0.120 |
Age_at_enrollment_days | 0.00033 | 1 (1–1) | 0.07 | −0.004 | 0.996 (0.98–1.0) | 0.465 |
Age | 0.11 | 1.1 (0.99–1.3) | 0.075 | 1.637 | 5.14 (0.085–309.385) | 0.433 |
Primary_tumor_site | −0.28 | 0.76 (0.35–1.6) | 0.47 | 1.502 | 4.492 (0.377–53.53) | 0.235 |
Efs_event | 2 | 7.7 (3.4–17) | 9.5e-07 | 3.941 | 51.476 (3.736–709.32) | 0.003 |
Tumor_content | 0.77 | 2.2 (0.57–8.2) | 0.26 | −0.562 | 0.57 (0.088–3.676) | 0.554 |
Description | ID | p Value | Count/Gene ID | |
---|---|---|---|---|
Downregulated | locomotion | GO:0040011 | 1.14 × 10−26 | CCL18/VCAN/MMP9/FAP/THBS1/CHN1/VCAM1/LOX/COL3A1/GPNMB/CDH2/SULF1/GJA1/ACTA2/TGFBR2/SMOC2/CCL21/MMP2/DCLK1/AKT3/CD200/MAP1B/RND3/KDR/MCC/LEF1/SGK1/SDC2/ENPP2/PECAM1/KITLG/CCR1/ADAMTS1/ITGA6/EPS8/ADAMTS9/EFNB2/CD34/THY1/SEMA6A/LYN/ALX1/S100A8/ITGA9/MTUS1/NRP1/PLVAP/PRKD1/ETS1/LYVE1/CDH5/PLXNC1/PODXL/ITGA2/FCER1G/TLR4/TEK/NRP2/PDGFRB/LAMB1/ELMO1/EMP2/MCTP1/FLT1/DOCK2/PTPRC/XBP1/CHL1/SATB2/PLXNA2/DLC1 |
angiogenesis | GO:0001525 | 4.39 × 10−26 | FAP/THBS1/GPNMB/SULF1/THBS2/PTPRB/TGFBR2/SMOC2/MMP2/CALCRL/CYBB/ADAM12/AKT3/ANPEP/KDR/LEF1/ENPP2/COL15A1/CEMIP2/TGFBI/APLNR/ADAMTS1/ADAMTS9/EFNB2/CD34/THY1/SEMA6A/SAT1/NRP1/PRKD1/ETS1/COL4A1/CDH5/EMCN/EPAS1/TEK/COL4A2/NRP2/PDGFRB/EMP2/FLT1/XBP1 | |
positive regulation of cell migration | GO:0030335 | 2.52 × 10−19 | MMP9/THBS1/GPNMB/ACTA2/TGFBR2/SMOC2/CCL21/MMP2/AKT3/KDR/LEF1/ENPP2/PECAM1/KITLG/CCR1/ADAMTS1/ITGA6/THY1/SEMA6A/LYN/NRP1/PLVAP/PRKD1/ETS1/LYVE1/CDH5/PODXL/ITGA2/TLR4/TEK/NRP2/PDGFRB/LAMB1/FLT1/PTPRC/XBP1 | |
cell differentiation | GO:0030154 | 6.24 × 10−16 | SPP1/VCAN/LPL/MMP9/CHN1/EFEMP1/COL12A1/VCAM1/LOX/COL3A1/DOCK11/CDH2/COL11A1/KRT10/SULF1/STEAP4/GJA1/A2M/ACTA2/TGFBR2/CCL21/MMP2/CD53/GPM6B/DCLK1/ADAM12/PLEK/MAP1B/ANPEP/KDR/ESRP1/LEF1/SGK1/SDC2/PECAM1/COL15A1/KITLG/CCR1/TGFBI/APLNR/ITGA6/MAP2/ADAMTS9/MTSS1/EFNB2/CD34/CD36/THY1/SEMA6A/LYN/HEY2/RAI14/ALX1/S100A8/RPS6KA2/SPRY4/NRP1/PRKD1/TMEM119/ETS1/PRICKLE1/COL4A1/CDH5/PLXNC1/PODXL/ITGA2/SLC6A6/EPAS1/FCER1G/TLR4/TEK/COL4A2/FRMD6/NRP2/PDGFRB/LAMB1/EMP2/FLT1/FARP1/DOCK2/PTPRC/XBP1/CHL1/RPS6KA3/SATB2/PLXNA2/TAGLN/BHLHE40 | |
extracellular matrix organization | GO:0030198 | 8.07 × 10−14 | LUM/MMP9/FAP/COL12A1/LOX/COL3A1/COL11A1/SULF1/SMOC2/MMP2/GPM6B/COL14A1/MMP16/COL15A1/TGFBI/ADAMTS1/ITGA6/ADAMTS9/ITGA9/FBLN5/COL4A1/ITGA2/COL4A2/LAMB1/NID2 | |
cell-substrate adhesion | GO:0031589 | 7.69 × 10−11 | THBS1/VCAM1/COL3A1/EDIL3/CCL21/GPM6B/VWF/KDR/ITGA6/ADAMTS9/CD34/CD36/THY1/SPRY4/NRP1/FBLN5/LYVE1/ITGA2/TEK/LAMB1/EMP2/NID2/DLC1 | |
chemotaxis | GO:0006935 | 7.74 × 10−11 | CCL18/THBS1/CHN1/VCAM1/LOX/GPNMB/SMOC2/CCL21/KDR/LEF1/ENPP2/CCR1/EFNB2/SEMA6A/LYN/S100A8/ITGA9/MTUS1/NRP1/PRKD1/PLXNC1/ITGA2/FCER1G/NRP2/PDGFRB/FLT1/DOCK2/CHL1/PLXNA2 | |
cell-matrix adhesion | GO:0007160 | 1.55 × 10−9 | THBS1/VCAM1/COL3A1/CCL21/GPM6B/KDR/ADAMTS9/CD34/CD36/THY1/NRP1/FBLN5/LYVE1/ITGA2/TEK/EMP2/NID2/DLC1 | |
cell-substrate junction assembly | GO:0007044 | 0.0002 | THBS1/GPM6B/KDR/ITGA6/THY1/NRP1/ITGA2/TEK/DLC1 | |
collagen-containing extracellular matrix | GO:0062023 | 3.43 × 10−21 | LUM/VCAN/MMP9/THBS1/EFEMP1/COL12A1/CTSC/COL3A1/CDH2/COL11A1/EDIL3/SULF1/A2M/THBS2/SMOC2/MMP2/VWF/COL14A1/SDC2/SPON1/PCOLCE/COL15A1/TGFBI/ADAMTS1/SPARCL/ADAMTS9/S100A8/BGN/HAPLN1/FBLN5/COL4A1/COL4A2/LAMB1/NID2 | |
extracellular exosome | GO:0070062 | 6.20 × 10−10 | LUM/SPP1/MMP9/THBS1/LYZ/HBB/EFEMP1/COL12A1/CTSC/VCAM1/PPIC/EDIL3/KRT10/STEAP4/A2M/ACTA2/CD53/VWF/ANPEP/MAN1A1/PECAM1/PCOLCE/COL15A1/CEMIP2/TGFBI/EPS8/PRSS23/THY1/LYN/S100A8/CD14/BGN/PLVAP/MYO1B/ENTPD1/FBLN5/LYVE1/RFTN1/PODXL/NT5E/FCGR3A/COL4A2/LAMB1/DOCK2/RAB27B/PTPRC/MARCKS/CHL1/NID2/TNFSF10/PYGL | |
collagen trimer | GO:0005581 | 1.90 × 10−6 | LUM/COL12A1/LOX/COL3A1/COL11A1/COL14A1/COL15A1/CD36/COL4A1/COL4A2 | |
collagen binding | GO:0005518 | 1.53 × 10−8 | LUM/MMP9/THBS1/LOX/VWF/COL14A1/PCOLCE/TGFBI/SPARCL1/ITGA2/NID2 | |
glycosaminoglycan binding | GO:0005539 | 3.92 × 10−8 | VCAN/LPL/THBS1/GPNMB/COL11A1/SULF1/THBS2/TGFBR2/SMOC2/PCOLCE/ADAMTS1/NRP1/BGN/HAPLN1/LYVE1/NRP2/PTPRC | |
Degradation of the extracellular matrix | REAC:R-HSA-1474228 | 6.00 × 10−8 | SPP1/MMP9/COL12A1/COL3A1/COL11A1/A2M/MMP2/COL14A1/MMP16/COL15A1/ADAMTS1/ADAMTS9/COL4A1/COL4A2/LAMB1 | |
Collagen formation | REAC:R-HSA-1474290 | 4.10 × 10−6 | MMP9/COL12A1/LOX/COL3A1/COL11A1/COL14A1/PCOLCE/COL15A1/ITGA6/COL4A1/COL4A2 | |
Collagen degradation | REAC:R-HSA-1442490 | 2.99 × 10−5 | MMP9/COL12A1/COL3A1/COL11A1/MMP2/COL14A1/COL15A1/COL4A1/COL4A2 | |
Collagen chain trimerization | REAC:R-HSA-8948216 | 0.0004 | COL12A1/COL3A1/COL11A1/COL14A1/COL15A1/COL4A1/COL4A2 |
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Yakushov, S.; Menyailo, M.; Denisov, E.; Karlina, I.; Zainullina, V.; Kirgizov, K.; Romantsova, O.; Timashev, P.; Ulasov, I. Identification of Factors Driving Doxorubicin-Resistant Ewing Tumor Cells to Survival. Cancers 2022, 14, 5498. https://doi.org/10.3390/cancers14225498
Yakushov S, Menyailo M, Denisov E, Karlina I, Zainullina V, Kirgizov K, Romantsova O, Timashev P, Ulasov I. Identification of Factors Driving Doxorubicin-Resistant Ewing Tumor Cells to Survival. Cancers. 2022; 14(22):5498. https://doi.org/10.3390/cancers14225498
Chicago/Turabian StyleYakushov, Semyon, Maxim Menyailo, Evgeny Denisov, Irina Karlina, Viktoria Zainullina, Kirill Kirgizov, Olga Romantsova, Peter Timashev, and Ilya Ulasov. 2022. "Identification of Factors Driving Doxorubicin-Resistant Ewing Tumor Cells to Survival" Cancers 14, no. 22: 5498. https://doi.org/10.3390/cancers14225498
APA StyleYakushov, S., Menyailo, M., Denisov, E., Karlina, I., Zainullina, V., Kirgizov, K., Romantsova, O., Timashev, P., & Ulasov, I. (2022). Identification of Factors Driving Doxorubicin-Resistant Ewing Tumor Cells to Survival. Cancers, 14(22), 5498. https://doi.org/10.3390/cancers14225498