Skip to content
2000
Volume 26, Issue 10
  • ISSN: 1389-4501
  • E-ISSN: 1873-5592

Abstract

Introduction

Breast cancer incidence and mortality have continued to rise over the past few decades. Despite advancements made in clinical research, the most imperative feature of breast cancer management is the diagnosis at the earliest stages. The current focus of the study is to identify and quantify differentially expressed oxidative stress-related proteins as putative early-stage markers for breast cancer.

Methods

Normal and cancerous breast tissue samples (n = 40) were collected after approval from the institutional bioethics committee (IBC) and with patient's consent. A label-free proteomic approach was used to quantify oxidative stress-related proteins. Gene expression of GSTP1, PRDX2, HSP90, NFE2L2, and miR-365a was quantified using RT-qPCR in all samples. Protein expression of PRDX2 and GSTP1 was further analyzed using immunohistochemistry.

Results

The protein and gene expression of PRDX2, GSTP1, and HSP90 were significantly upregulated ( < 0.05) in cancerous samples as compared to normal. However, gene and protein expression of the transcription factor NFE2L2 was significantly downregulated ( < 0.05) in diseased samples. OncomiR-365a was also significantly upregulated ( < 0.05) in cancerous samples. Immunohistochemical analysis also confirmed the upregulated expression of GSTP1 and PRDX2 in cancer tissues.

Discussion

Our study provides insight into the significant role of GSTP1, PRDX2, and NFE2L2 in the pathophysiology of the disease as early-stage breast cancer markers. It is suggested that altered expression of these key proteins could play a protective role in reducing the damage.

Conclusion

It can be concluded that GSTP1, PRDX2, and NFE2L2 may serve as predictive early-stage markers for diagnosis and potential therapeutic targets for breast cancer.

Loading

Article metrics loading...

/content/journals/cdt/10.2174/0113894501393175250627013915
2025-07-04
2025-10-13
Loading full text...

Full text loading...

References

  1. NeaguA.N. WhithamD. BuonannoE. JenkinsA. Alexa-StratulatT. TambaB.I. DarieC.C. Proteomics and its applications in breast cancer.Am. J. Cancer Res.20211194006404934659875
    [Google Scholar]
  2. JafariS.H. SaadatpourZ. SalmaninejadA. MomeniF. MokhtariM. NahandJ.S. RahmatiM. MirzaeiH. KianmehrM. Breast cancer diagnosis: Imaging techniques and biochemical markers.J. Cell. Physiol.201823375200521310.1002/jcp.2637929219189
    [Google Scholar]
  3. ShimomuraA. ShiinoS. KawauchiJ. TakizawaS. SakamotoH. MatsuzakiJ. OnoM. TakeshitaF. NiidaS. ShimizuC. FujiwaraY. KinoshitaT. TamuraK. OchiyaT. Novel combination of serum microRNA for detecting breast cancer in the early stage.Cancer Sci.2016107332633410.1111/cas.1288026749252
    [Google Scholar]
  4. PisoschiA.M. PopA. The role of antioxidants in the chemistry of oxidative stress: A review.Eur. J. Med. Chem.201597557410.1016/j.ejmech.2015.04.04025942353
    [Google Scholar]
  5. ArfinS. JhaN.K. JhaS.K. KesariK.K. RuokolainenJ. RoychoudhuryS. RathiB. KumarD. Oxidative stress in cancer cell metabolism.Antioxidants202110564267010.3390/antiox1005064233922139
    [Google Scholar]
  6. WangR. LiangL. MatsumotoM. IwataK. UmemuraA. HeF. Reactive oxygen species and NRF2 signaling, friends or foes in cancer?Biomolecules202313235337510.3390/biom1302035336830722
    [Google Scholar]
  7. HeF. AntonucciL. KarinM. NRF2 as a regulator of cell metabolism and inflammation in cancer.Carcinogenesis202041440541610.1093/carcin/bgaa03932347301
    [Google Scholar]
  8. PanieriE. PinhoS.A. AfonsoG.J.M. OliveiraP.J. Cunha-OliveiraT. SasoL. NRF2 and mitochondrial function in cancer and cancer stem cells.Cells20221115240110.3390/cells1115240135954245
    [Google Scholar]
  9. World medical association declaration of helsinki – ethical principles for medical research involving human subjects.JAMA2013310202191219424141714
    [Google Scholar]
  10. GinsburgO. YipC.H. BrooksA. CabanesA. CaleffiM. Dunstan YatacoJ.A. GyawaliB. McCormackV. McLaughlin de AndersonM. MehrotraR. MoharA. MurilloR. PaceL.E. PaskettE.D. RomanoffA. RositchA.F. ScheelJ.R. SchneidmanM. Unger-SaldañaK. VanderpuyeV. WuT.Y. YumaS. DvaladzeA. DugganC. AndersonB.O. Breast cancer early detection: A phased approach to implementation.Cancer2020126S10Suppl. 102379239310.1002/cncr.3288732348566
    [Google Scholar]
  11. KangariP. Zarnoosheh FarahanyT. GolchinA. EbadollahzadehS. SalmaninejadA. MahboobS.A. NourazarianA. Enzymatic antioxidant and lipid peroxidation evaluation in the newly diagnosed breast cancer patients in Iran.Asian Pac. J. Cancer Prev.201819123511351510.31557/APJCP.2018.19.12.351130583677
    [Google Scholar]
  12. HauckA.K. BernlohrD.A. Oxidative stress and lipotoxicity.J. Lipid Res.201657111976198610.1194/jlr.R06659727009116
    [Google Scholar]
  13. TsaiM.C. HuangT.L. Increased activities of both superoxide dismutase and catalase were indicators of acute depressive episodes in patients with major depressive disorder.Psychiatry Res.2016235384210.1016/j.psychres.2015.12.00526677733
    [Google Scholar]
  14. GalassoM. GambinoS. RomanelliM.G. DonadelliM. ScupoliM.T. Browsing the oldest antioxidant enzyme: Catalase and its multiple regulation in cancer.Free Radic. Biol. Med.202117226427210.1016/j.freeradbiomed.2021.06.01034129927
    [Google Scholar]
  15. LabordeE. Glutathione transferases as mediators of signaling pathways involved in cell proliferation and cell death.Cell Death Differ.20101791373138010.1038/cdd.2010.8020596078
    [Google Scholar]
  16. YangS. WangD. LiJ. XuH. ShenH. ChenX. ZhouS. ZhongS. ZhaoJ. TangJ. Predictive role of GSTP1-containing exosomes in chemotherapy-resistant breast cancer.Gene201762351410.1016/j.gene.2017.04.03128438694
    [Google Scholar]
  17. DesmetzC. Bascoul-MolleviC. RochaixP. LamyP.J. KramarA. RouanetP. MaudelondeT. MangéA. SolassolJ. Identification of a new panel of serum autoantibodies associated with the presence of in situ carcinoma of the breast in younger women.Clin. Cancer Res.200915144733474110.1158/1078‑0432.CCR‑08‑330719584157
    [Google Scholar]
  18. ChenY. YangS. ZhouH. SuD. PRDX2 promotes the proliferation and metastasis of non-small cell lung cancer in vitro and in vivo .BioMed Res. Int.202020201835986010.1155/2020/835986032908916
    [Google Scholar]
  19. StresingV. BaltziskuetaE. RubioN. BlancoJ. ArribaM. VallsJ. JanierM. ClézardinP. Sanz-PamplonaR. NievaC. MarroM. DmitriP. SierraA. Peroxiredoxin 2 specifically regulates the oxidative and metabolic stress response of human metastatic breast cancer cells in lungs.Oncogene201332672473510.1038/onc.2012.9322430214
    [Google Scholar]
  20. HashimZ IlyasA ZarinaS Therapeutic effect of hydrogen peroxide via altered expression of glutathione S-transferase and peroxiredoxin-2 in hepatocellular carcinoma.Hepatobiliary Pancreat Dis Int202019325826510.1016/j.hbpd.2020.03.00632284258
    [Google Scholar]
  21. NguyenT. SherrattP.J. PickettC.B. Regulatory mechanisms controlling gene expression mediated by the antioxidant response element.Annu. Rev. Pharmacol. Toxicol.200343123326010.1146/annurev.pharmtox.43.100901.14022912359864
    [Google Scholar]
  22. KasparJ.W. NitureS.K. JaiswalA.K. Nrf2:INrf2 (Keap1) signaling in oxidative stress.Free Radic. Biol. Med.20094791304130910.1016/j.freeradbiomed.2009.07.03519666107
    [Google Scholar]
  23. KimK.C. KangK.A. ZhangR. PiaoM.J. KimG.Y. KangM.Y. LeeS.J. LeeN.H. SurhY.J. HyunJ.W. Up-regulation of Nrf2-mediated heme oxygenase-1 expression by eckol, a phlorotannin compound, through activation of Erk and PI3K/Akt.Int. J. Biochem. Cell Biol.201042229730510.1016/j.biocel.2009.11.00919931411
    [Google Scholar]
  24. MaY.F. WuZ.H. GaoM. LoorJ.J. Nuclear factor erythroid 2-related factor 2 antioxidant response element pathways protect bovine mammary epithelial cells against H2O2-induced oxidative damage in vitro .J. Dairy Sci.201810165329534410.3168/jds.2017‑1412829573798
    [Google Scholar]
  25. UpadhayayS. MehanS. Targeting Nrf2/HO-1 anti-oxidant signaling pathway in the progression of multiple sclerosis and influences on neurological dysfunctions.Brain Disord.2021310001910003510.1016/j.dscb.2021.100019
    [Google Scholar]
  26. ShihY.Y. LinH.Y. JanH.M. ChenY.J. OngL.L. YuA.L.T. LinC.H. S-glutathionylation of Hsp90 enhances its degradation and correlates with favorable prognosis of breast cancer.Redox Biol.20225710250110251110.1016/j.redox.2022.10250136279628
    [Google Scholar]
  27. NgoV. BrickendenA. LiuH. YeungC. ChoyW.Y. DuennwaldM.L. A novel yeast model detects Nrf2 and Keap1 interactions with Hsp90.Dis. Model. Mech.2022154dmm049235dmm04925810.1242/dmm.04925835088844
    [Google Scholar]
  28. MoJ.L. PanZ.G. ChenX. LeiY. LvL.L. QianC. SunF.Y. MicroRNA-365 knockdown prevents ischemic neuronal injury by activating oxidation resistance 1-mediated antioxidant signals.Neurosci. Bull.201935581582510.1007/s12264‑019‑00371‑y30977043
    [Google Scholar]
  29. WangY. ZhangS. BaoH. MuS. ZhangB. MaH. MaS. MicroRNA-365 promotes lung carcinogenesis by downregulating the USP33/SLIT2/ROBO1 signalling pathway.Cancer Cell Int.20181816410.1186/s12935‑018‑0563‑629743814
    [Google Scholar]
  30. LiuY.P. HengJ.Y. ZhaoX.Y. LiE.Y. The inhibition of circular RNA circNOLC1 by propofol/STAT3 attenuates breast cancer stem cells function via miR-365a-3p/STAT3 signaling.J. Transl. Med.202119146710.1186/s12967‑021‑03133‑534789263
    [Google Scholar]
  31. YinL. XiaoX. GeorgikouC. YinY. LiuL. KarakhanovaS. LuoY. GladkichJ. FellenbergJ. StichtC. GretzN. GrossW. HerrI. MicroRNA-365a-3p inhibits c-Rel-mediated NF-κB signaling and the progression of pancreatic cancer.Cancer Lett.201945220321210.1016/j.canlet.2019.03.02530910589
    [Google Scholar]
  32. GaoM. LiuL. ZhangD. YangY. ChangZ. Long non-coding RNA NEAT1 serves as sponge for miR-365a-3p to promote gastric cancer progression via regulating ABCC4.OncoTargets Ther.2020133977398510.2147/OTT.S24555732494153
    [Google Scholar]
  33. HongY. XinC. ZhengH. HuangZ. YangY. ZhouJ. GaoX. HaoL. LiuQ. ZhangW. HaoL. miR-365a-3p regulates ADAM10-JAK-STAT signaling to suppress the growth and metastasis of colorectal cancer cells.J. Cancer202011123634364410.7150/jca.4273132284760
    [Google Scholar]
  34. GaiC. LiuC. WuX. YuM. ZhengJ. ZhangW. LvS. LiW. MT1DP loaded by folate-modified liposomes sensitizes erastin-induced ferroptosis via regulating miR-365a-3p/NRF2 axis in non-small cell lung cancer cells.Cell Death Dis.202011975176210.1038/s41419‑020‑02939‑332929075
    [Google Scholar]
  35. KhanzodeS.S. MuddeshwarM.G. KhanzodeS.D. DakhaleG.N. Antioxidant enzymes and lipid peroxidation in different stages of breast cancer.Free Radic. Res.2004381818510.1080/0141159031000163706615061657
    [Google Scholar]
  36. ShahiY. SamadiF.M. MukherjeeS. Plasma lipid peroxidation and antioxidant status in patients with oral precancerous lesions and oral cancer.Oral Sci. Int.2020172869310.1002/osi2.1050
    [Google Scholar]
/content/journals/cdt/10.2174/0113894501393175250627013915
Loading
/content/journals/cdt/10.2174/0113894501393175250627013915
Loading

Data & Media loading...


  • Article Type:
    Research Article
Keyword(s): Breast cancer; early stage markers; GSTP1; NFE2L2; oxidative stress; PRDX2
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test