Predictive and Prognostic Significance of MRNA Expression and DNA Copies Aberrations of , , , , , , and Genes in Patients with Breast Cancer

Overview

Journal Diagnostics (Basel)

Specialty Radiology

Date 2022 Feb 25

PMID 35204496

Authors

Matvey M Tsyganov

Marina K Ibragimova

Evgeniy Yu Garbukov

Irina A Tsydenova

Kseniya A Gaptulbarova

Daria S Dolgasheva

Ekaterina A Zdereva

Anastasia A Frolova

Elena M Slonimskaya

Nikolai V Litviakov

Affiliations

Soon will be listed here.

Abstract

Material And Methods: The study involved 97 patients with luminal B breast cancer IIB-IIIB stages. DNA and RNA were isolated from samples of tumor tissue before and after treatment. Microarray analysis was performed for all samples on high-density microarrays (DNA chips) of Affymetrix (USA) CytoScanTM HD Array and Clariom™ S Assay, human. Detection of expression level of seven chemosensitivity genes-, , , , , , and -was performed using PCR real-time (RT-qPCR).

Results: The expression of the (AC scheme), , , and genes in patients with an objective response to treatment (complete and partial regression) is higher than in patients with stabilization and progression ( 0.05). According to our results, the presence of a high level of in a tumor biopsy is associated with the low efficiency of the NAC CP scheme ( 0.05). The presence of deletion is associated with complete and partial regression, as for the and genes ( 0.05). Higher rates of metastatic survival are associated with a high level of expression and amplification of the gene (log-rank test 0.02 and 0.05).

Conclusion: Thus, a complex assessment of the chemotherapy's gene expression is important not only for understanding the heterogeneity and molecular biology of breast cancer but also to obtain a more accurate disease prognosis.

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References

Katsetos C, Herman M, Mork S . Class III beta-tubulin in human development and cancer. Cell Motil Cytoskeleton. 2003; 55(2):77-96. DOI: 10.1002/cm.10116. View

Chen J, Chien H, Chen K, Hwang C, Chen H, Yeh K . Amplification of HER2 and TOP2A and deletion of TOP2A genes in a series of Taiwanese breast cancer. Medicine (Baltimore). 2017; 96(2):e5582. PMC: 5266154. DOI: 10.1097/MD.0000000000005582. View

Zhang J, Wu Y, Hu X, Wang B, Wang L, Zhang S . GSTT1, GSTP1, and GSTM1 genetic variants are associated with survival in previously untreated metastatic breast cancer. Oncotarget. 2017; 8(62):105905-105914. PMC: 5739688. DOI: 10.18632/oncotarget.22450. View

Soong R, Shah N, Salto-Tellez M, Tai B, Soo R, Han H . Prognostic significance of thymidylate synthase, dihydropyrimidine dehydrogenase and thymidine phosphorylase protein expression in colorectal cancer patients treated with or without 5-fluorouracil-based chemotherapy. Ann Oncol. 2008; 19(5):915-9. PMC: 2931808. DOI: 10.1093/annonc/mdm599. View

Kakimoto M, Uetake H, Osanai T, Shirota Y, Takagi Y, Takeshita E . Thymidylate synthase and dihydropyrimidine dehydrogenase gene expression in breast cancer predicts 5-FU sensitivity by a histocultural drug sensitivity test. Cancer Lett. 2005; 223(1):103-11. DOI: 10.1016/j.canlet.2004.09.020. View

Abdel-Fatah T, Ali R, Sadiq M, Moseley P, Mesquita K, Ball G . ERCC1 Is a Predictor of Anthracycline Resistance and Taxane Sensitivity in Early Stage or Locally Advanced Breast Cancers. Cancers (Basel). 2019; 11(8). PMC: 6721618. DOI: 10.3390/cancers11081149. View

Nami B, Wang Z . Genetics and Expression Profile of the Tubulin Gene Superfamily in Breast Cancer Subtypes and Its Relation to Taxane Resistance. Cancers (Basel). 2018; 10(8). PMC: 6116153. DOI: 10.3390/cancers10080274. View

Li J, Sun P, Huang T, He S, Li L, Xue G . Individualized chemotherapy guided by the expression of and genes versus classic chemotherapy in the treatment of breast cancer: A comparative effectiveness study. Oncol Lett. 2020; 21(1):21. PMC: 7681196. DOI: 10.3892/ol.2020.12282. View

Horlings H, Lai C, Nuyten D, Halfwerk H, Kristel P, van Beers E . Integration of DNA copy number alterations and prognostic gene expression signatures in breast cancer patients. Clin Cancer Res. 2010; 16(2):651-63. DOI: 10.1158/1078-0432.CCR-09-0709. View

10.

Yang S, Wang D, Li J, Xu H, Shen H, Chen X . Predictive role of GSTP1-containing exosomes in chemotherapy-resistant breast cancer. Gene. 2017; 623:5-14. DOI: 10.1016/j.gene.2017.04.031. View

11.

Zhao J, Zhang H, Lei T, Liu J, Zhang S, Wu N . Drug resistance gene expression and chemotherapy sensitivity detection in Chinese women with different molecular subtypes of breast cancer. Cancer Biol Med. 2020; 17(4):1014-1025. PMC: 7721095. DOI: 10.20892/j.issn.2095-3941.2020.0157. View

12.

Song B, Wang L, Zhang Y, Li N, Dai H, Xu H . Combined Detection of HER2, Ki67, and GSTP1 Genes on the Diagnosis and Prognosis of Breast Cancer. Cancer Biother Radiopharm. 2018; 34(2):85-90. DOI: 10.1089/cbr.2018.2570. View

13.

Duffy M, Crown J . A personalized approach to cancer treatment: how biomarkers can help. Clin Chem. 2008; 54(11):1770-9. DOI: 10.1373/clinchem.2008.110056. View

14.

Li J, Sun P, Huang T, He S, Li L, Xue G . Extensive analysis of the molecular biomarkers excision repair cross complementing 1, ribonucleotide reductase M1, β-tubulin III, thymidylate synthetase, and topoisomerase IIα in breast cancer: Association with clinicopathological characteristics. Medicine (Baltimore). 2021; 100(14):e25344. PMC: 8036124. DOI: 10.1097/MD.0000000000025344. View

15.

Wang Y, Sparano J, Fineberg S, Stead L, Sunkara J, Horwitz S . High expression of class III β-tubulin predicts good response to neoadjuvant taxane and doxorubicin/cyclophosphamide-based chemotherapy in estrogen receptor-negative breast cancer. Clin Breast Cancer. 2012; 13(2):103-8. PMC: 4039021. DOI: 10.1016/j.clbc.2012.11.003. View

16.

Zhong W, Yang Y, Zhang A, Lin W, Liang G, Ling Y . Prognostic and predictive value of the combination of TOP2A and HER2 in node-negative tumors 2 cm or smaller (T1N0) breast cancer. Breast Cancer. 2020; 27(6):1147-1157. DOI: 10.1007/s12282-020-01142-8. View

17.

Bepler G, Williams C, Schell M, Chen W, Zheng Z, Simon G . Randomized international phase III trial of ERCC1 and RRM1 expression-based chemotherapy versus gemcitabine/carboplatin in advanced non-small-cell lung cancer. J Clin Oncol. 2013; 31(19):2404-12. PMC: 3691357. DOI: 10.1200/JCO.2012.46.9783. View

18.

OMalley F, Chia S, Tu D, Shepherd L, Levine M, Huntsman D . Topoisomerase II alpha protein and responsiveness of breast cancer to adjuvant chemotherapy with CEF compared to CMF in the NCIC CTG randomized MA.5 adjuvant trial. Breast Cancer Res Treat. 2011; 128(2):401-9. DOI: 10.1007/s10549-011-1511-5. View

19.

Zhou F, Yu Z, Jiang T, Lv H, Yao R, Liang J . Genetic polymorphisms of GSTP1 and XRCC1: prediction of clinical outcome of platinum-based chemotherapy in advanced non-small cell lung cancer (NSCLC) patients. Swiss Med Wkly. 2011; 141:w13275. DOI: 10.4414/smw.2011.13275. View

20.

Pfaffl M . A new mathematical model for relative quantification in real-time RT-PCR. Nucleic Acids Res. 2001; 29(9):e45. PMC: 55695. DOI: 10.1093/nar/29.9.e45. View