Whole Transcriptome Analysis of Breast Cancer Tumors during Neoadjuvant Chemotherapy: Association with Hematogenous Metastasis
Abstract
:1. Introduction
2. Results
2.1. Comparison of the Expression Profile of Patients with Breast Cancer before and after Preoperative Chemotherapy
2.2. Comparison of the Expression Profiles of Patients with Breast Cancer before and after Preoperative Chemotherapy Depending on the Status of Hematogenous Metastasis
2.3. Validation of the Association of Genes with Hematogenous Metastasis in Patients with Breast Cancer
3. Discussion
4. Materials and Methods
4.1. IHC Molecular Subtype Analysis
4.2. Microarray Analysis
4.3. DEG Identification
4.4. Identification of Significant Signaling Pathways
4.5. Study Design
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Upregulated DEGs | Exp. Levels (log2) | Genomic Location | |
---|---|---|---|
Before NAC | After NAC | ||
DUSP1 (Dual Specificity Phosphatase 1) | 5.38 | 7.94 | 5q35.1 |
DCDC2 (Doublecortin Domain Containing 2) | 7.1 | 9.2 | 6p22.3 |
FOS (Fos Proto-oncogene, AP-1 Transcription Factor Subunit) | 7.4 | 9.1 | 14q24.3 |
NR4A3 (Nuclear Receptor Subfamily 4 Group A Member 3) | 6.38 | 8.03 | 9q22 |
CYR61 (Cellular Communication Network Factor 1) | 7.56 | 9.06 | 1p22.3 |
PTGS2 (Prostaglandin-Endoperoxide Synthase 2) | 6.36 | 7.78 | 1q31.1 |
MGARP (Mitochondria Localized Glutamic Acid Rich Protein) | 6 | 7.41 | 4q31.1 |
MGMT (O-6-Methylguanine-DNA Methyltransferase) | 8.94 | 10.25 | 10q26.3 |
ENDOD1 (Endonuclease Domain Containing 1) | 7.15 | 8.3 | 11q21 |
SHH (Sonic Hedgehog Signaling Molecule) | 4.9 | 5.95 | 7q36.3 |
Downregulated DEGs | |||
H2AFX (H2A.X Variant Histone) | 10.59 | 8.38 | 11q23.3 |
HIST1H2BL (H2B Clustered Histone 13) | 10.47 | 8.45 | 6p22.1 |
MKI67 (Marker Of Proliferation Ki-67) | 10.47 | 8.72 | 10q26.2 |
CENPF (Centromere Protein F) | 9.63 | 8.09 | 1q41 |
UBE2C (Ubiquitin Conjugating Enzyme E2 C) | 10.66 | 9.13 | 20q13.12 |
RARA (Retinoic Acid Receptor Alpha) | 10.34 | 8.89 | 17q21.2 |
BOP1 (BOP1 Ribosomal Biogenesis Factor) | 9.5 | 8.22 | 8q24.3 |
TROAP (Trophinin Associated Protein) | 7.33 | 6.16 | 12q13.12 |
OR10Q1 (Olfactory Receptor Family 10 Subfamily Q Member 1) | 6.48 | 5.45 | 11q12.1 |
NKAIN1 (Sodium/Potassium Transporting ATPase Interacting 1) | 8 | 6.98 | 1p35.2 |
Upregulated DEGs | Exp. Levels (log2) | Genomic Location | |
---|---|---|---|
No Mts | Yes Mts | ||
VWC2L (Von Willebrand Factor C Domain Containing 2 Like) | 5.13 | 6.9 | 2q34-q35 |
MTA3 (Metastasis Associated 1 Family Member 3) | 5.21 | 6.67 | 2p21 |
CHN2 (Chimerin 2) | 6.23 | 7.62 | 7p14.3 |
GRXCR2 (Glutaredoxin And Cysteine Rich Domain Containing 2) | 4.79 | 6.25 | 5q32 |
SPAG5 (Sperm Associated Antigen 5) | 5.19 | 6.59 | 17q11.2 |
IL19 (Interleukin 19) | 5.86 | 8.08 | 1q32.1 |
RAB41 (Member RAS Oncogene Family) | 4.52 | 6.01 | Xq13.1 |
ABCB4 (ATP Binding Cassette Subfamily B Member 4) | 5.7 | 7.1 | 7q21.12 |
HIST1H2BB (H2B Clustered Histone 3) | 6.66 | 8.67 | 6p22.2 |
HIST1H2BI (H2B Clustered Histone 10) | 5.36 | 7.39 | 6p22.2 |
Downregulated DEGs | |||
MGMT (O-6-Methylguanine-DNA Methyltransferase) | 10.01 | 8.26 | 10q26.3 |
PTGIS (Prostaglandin I2 Synthase) | 9.82 | 8.1 | 20q13.13 |
INIP (INTS3 And NABP Interacting Protein) | 10.78 | 8.8 | 9q32 |
HLA-E (Major Histocompatibility Complex, Class I, E) | 11.21 | 8.93 | 6p22.1 |
LRIG3 (Leucine-Rich Repeats and Immunoglobulin-Like Domains 3) | 8.71 | 6.65 | 12q14.1 |
EHD2 (EH Domain Containing 2) | 11.67 | 8.34 | 19q13.33 |
EPPK1 (Epiplakin 1) | 11.07 | 9.17 | 8q24.3 |
CITED2 (Cbp/P300 Interacting Transactivator With Glu/Asp Rich Carboxy-Terminal Domain 2) | 11.05 | 8.95 | 6q24.1 |
MCAT (Malonyl-CoA-Acyl Carrier Protein Transacylase) | 9.38 | 7.43 | 22q13.2 |
REEP6 (Receptor Accessory Protein 6) | 12.13 | 8.83 | 19p13.3 |
Upregulated DEGs | Exp. Levels (log2) | Genomic Location | |
---|---|---|---|
No Mts | Yes Mts | ||
OLIG1 (Oligodendrocyte Transcription Factor 1) | 4.69 | 5.98 | 21q22.11 |
TNFSF13 (TNF Superfamily Member 13) | 7.53 | 8.67 | 17p13.1 |
ST7-AS1 (ST7 Antisense RNA 1) | 6.24 | 7.25 | 7q31.2 |
ZNF165 (Zinc Finger Protein 165) | 6.01 | 7.11 | 6p22.1 |
PPP1R9A (Protein Phosphatase 1 Regulatory Subunit 9A) | 7.93 | 9.26 | 7q21.3 |
OR9K2 (Olfactory Receptor Family 9 Subfamily K Member 2) | 7 | 8.3 | 12q13.2 |
MFSD4 (Major Facilitator Superfamily Domain Containing 4A) | 5.99 | 7.31 | 1q32.1 |
Downregulated DEGs | |||
ATG16L1 (Autophagy Related 16 Like 1) | 7.19 | 5.46 | 2q37.1 |
CD4 (CD4 Molecule) | 7.61 | 5.76 | 12p13.31 |
GPR153 (G Protein-Coupled Receptor 153) | 8.74 | 7.51 | 1p36.31 |
FAM89B (Family With Sequence Similarity 89 Member B) | 9.14 | 7.7 | 11q13.1 |
RAB29 (Member RAS Oncogene Family) | 7.87 | 6.79 | 1q32.1 |
ARL2-SNX15 (Readthrough (NMD Candidate)) | 8.85 | 7.8 | 11q13.1 |
PLEKHM2 (Pleckstrin Homology And Domain Containing M2) | 9.37 | 8.32 | 1p36.21 |
COL11A1 (Collagen Type XI Alpha 1 Chain) | 11.11 | 9.36 | 1p21.1 |
GYPC (Glycophorin C (Gerbich Blood Group)) | 10.44 | 9.39 | 2q14.3 |
GREM1 (Gremlin 1, DAN Family BMP Antagonist) | 9.97 | 8.86 | 15q13.3 |
LGALS9B (Galectin 9B) | 9.56 | 8.45 | 17p11.2 |
NDP (Norrin Cystine Knot Growth Factor NDP) | 7.8 | 6.67 | Xp11.3 |
ICMT (PPMT) (Isoprenylcysteine Carboxyl Methyltransferase) | 10.54 | 8.56 | 1p36.31 |
RBM43 (RNA Binding Motif Protein 43) | 8.1 | 6.99 | 2q23.3 |
Clinical and Morphological Parameter | The Number of Patients, abs.n. (%) | |
---|---|---|
Menstrual status | Premenopause | 22 (56.4%) |
Postmenopause | 17 (43.6%) | |
Histological type | Invasive ductal carcinoma | 34 (87.2%) |
Invasive lobular carcinoma | 2 (5.1%) | |
Other types | 3 (7.7%) | |
Tumor size | T1-2 | 36 (92.3%) |
T3-4 | 3 (7.7%) | |
Lymphogenous metastasis | N0 | 16 (41.0%) |
N1-2 | 23 (58.9%) | |
Hematogenous metastasis | Yes | 16 (41.0%) |
No | 23 (59.0%) | |
NAC regimen | CAX | 8 (20.5%) |
АС | 18 (46.1%) | |
Taxotere in mono | 6 (15.4%) | |
АТ/АСТ | 3 (7.7%) | |
CP | 4 (10.3%) | |
NAC effect | Progression and stabilization | 12 (30.8%) |
Partial regression | 27 (69.2%) | |
Median observation | 64 [14; 144] | 39 (100%) |
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Ibragimova, M.K.; Tsyganov, M.M.; Litviakov, N.V. Whole Transcriptome Analysis of Breast Cancer Tumors during Neoadjuvant Chemotherapy: Association with Hematogenous Metastasis. Int. J. Mol. Sci. 2022, 23, 13906. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms232213906
Ibragimova MK, Tsyganov MM, Litviakov NV. Whole Transcriptome Analysis of Breast Cancer Tumors during Neoadjuvant Chemotherapy: Association with Hematogenous Metastasis. International Journal of Molecular Sciences. 2022; 23(22):13906. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms232213906
Chicago/Turabian StyleIbragimova, Marina K., Matvey M. Tsyganov, and Nikolai V. Litviakov. 2022. "Whole Transcriptome Analysis of Breast Cancer Tumors during Neoadjuvant Chemotherapy: Association with Hematogenous Metastasis" International Journal of Molecular Sciences 23, no. 22: 13906. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms232213906