Skip to content
2000
Volume 28, Issue 6
  • ISSN: 1386-2073
  • E-ISSN: 1875-5402

Abstract

Background

The tumor microenvironment (TME) exerts a significant influence on the development, invasion, metastasis, and drug resistance of breast cancer. Therefore, this study sought to investigate potential prognostic factors and markers indicative of TME remodeling in breast cancer, utilizing data from the TCGA database.

Methods

In this study, transcriptome RNA-seq data from 1222 breast cancer samples were processed using CIBERSORT and ESTIMATE algorithms. We conducted a differential gene expression analysis utilizing COX regression analysis and constructed protein-protein interaction (PPI) networks for enhanced visualization. Through univariate COX analysis and cross-analysis within PPI networks, the Interleukin-7 receptor (IL-7R) emerged as a potential predictor. Subsequently, we performed a comprehensive investigation encompassing single-gene survival analysis, clinical correlation assessment, and GSEA enrichment analysis targeting IL-7R as a core gene associated with prognosis. We examined the expression of IL-7R in human breast cancer and normal breast tissue through clinical studies and cytology experiments, followed by an in-depth analysis of the relationship between IL-7R and breast cancer.

Results

The survival analysis revealed that breast cancer patients with elevated IL-7R expression experienced prolonged survival compared to those with lower IL-7R levels. Results obtained from the Wilcoxon rank-sum test, along with clinical and cellular experiments, indicated higher IL-7R expression in tumor samples compared to normal samples. Correlation tests conducted between IL-7R expression and clinicopathological stage characteristics highlighted statistically significant associations between IL-7R expression and the T and M stages. Additionally, cell classification analysis of tumor-infiltrating immune cells (TIC) proportion showed that activated CD4+ T cells and CD8 T cells of memory B cells were positively correlated with IL-7R expression. These findings further underscored the impact of IL-7R levels on the tumor microenvironment (TME).

Conclusion

IL-7R emerges as a potential prognostic indicator for breast cancer patients, particularly in sustaining the immunoactive status of the tumor microenvironment (TME) and contributing to immune reconstitution. These findings offer novel insights into breast cancer treatment strategies.

© 2025 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/cchts/10.2174/0113862073293963240409040110
2024-04-17
2025-09-11

  • From This Site

    /content/journals/cchts/10.2174/0113862073293963240409040110
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. UllahF.M. Breast cancer: Current perspectives on the disease status.Adv. Exp. Med. Biol.20191152516410.1007/978‑3‑030‑20301‑6_4 31456179
     [Google Scholar]
  2. GuanghuiR. XiaoyanH. ShuyiY. JunC. GuobinQ. An efficient or methodical review of immunotherapy against breast cancer.J. Biochem. Mol. Toxicol.2019338e2233910.1002/jbt.22339 31157481
     [Google Scholar]
  3. DeepakK.G.K. VempatiR. NagarajuG.P. DasariV.R. S, N.; Rao, D.N.; Malla, R.R. Tumor microenvironment: Challenges and opportunities in targeting metastasis of triple negative breast cancer.Pharmacol. Res.202015310468310.1016/j.phrs.2020.104683 32050092
     [Google Scholar]
  4. ChenF. ChenJ. YangL. LiuJ. ZhangX. ZhangY. TuQ. YinD. LinD. WongP.P. HuangD. XingY. ZhaoJ. LiM. LiuQ. SuF. SuS. SongE. Extracellular vesicle-packaged HIF-1α-stabilizing lncRNA from tumour-associated macrophages regulates aerobic glycolysis of breast cancer cells.Nat. Cell Biol.201921449851010.1038/s41556‑019‑0299‑0 30936474
     [Google Scholar]
  5. KhalafK. HanaD. ChouJ.T.T. SinghC. MackiewiczA. KaczmarekM. Aspects of the tumor microenvironment involved in immune resistance and drug resistance.Front. Immunol.20211265636410.3389/fimmu.2021.656364 34122412
     [Google Scholar]
  6. HessmannE. BuchholzS.M. DemirI.E. SinghS.K. GressT.M. EllenriederV. NeesseA. Microenvironmental determinants of pancreatic cancer.Physiol. Rev.202010041707175110.1152/physrev.00042.2019 32297835
     [Google Scholar]
  7. JinM.Z. JinW.L. The updated landscape of tumor microenvironment and drug repurposing.Signal Transduct. Target. Ther.20205116610.1038/s41392‑020‑00280‑x 32843638
     [Google Scholar]
  8. YangP. ChenW. XuH. YangJ. JiangJ. JiangY. XuG. Correlation of CCL8 expression with immune cell infiltration of skin cutaneous melanoma: Potential as a prognostic indicator and therapeutic pathway.Cancer Cell Int.202121163510.1186/s12935‑021‑02350‑8 34844613
     [Google Scholar]
  9. LiE. YangX. DuY. WangG. ChanD.W. WuD. XuP. NiP. XuD. HuY. Cxcl8 associated dendritic cell activation marker expression and recruitment as indicators of favorable outcomes in colorectal cancer.Front. Immunol.20211266717710.3389/fimmu.2021.667177 34025668
     [Google Scholar]
  10. BeguinotM. DauplatM.M. KwiatkowskiF. LebouedecG. TixierL. PomelC. LlorcaP.F. RobinR.N. Analysis of tumour-infiltrating lymphocytes reveals two new biologically different subgroups of breast ductal carcinoma in situ.BMC Cancer201818112910.1186/s12885‑018‑4013‑6 29394917
     [Google Scholar]
  11. KimA. HeoS.H. KimY.A. GongG. Jin LeeH. An examination of the local cellular immune response to examples of both ductal carcinoma in situ (dcis) of the breast and dcis with microinvasion, with emphasis on tertiary lymphoid structures and tumor infiltrating lymphoctytes.Am. J. Clin. Pathol.2016146113714410.1093/ajcp/aqw097 27402610
     [Google Scholar]
  12. MehrajU. DarA.H. WaniN.A. MirM.A. Tumor microenvironment promotes breast cancer chemoresistance.Cancer Chemother. Pharmacol.202187214715810.1007/s00280‑020‑04222‑w 33420940
     [Google Scholar]
  13. Al-RawiM.A.A. RmaliK. WatkinsG. ManselR.E. JiangW.G. Aberrant expression of interleukin-7 (IL-7) and its signalling complex in human breast cancer.Eur. J. Cancer200440449450210.1016/j.ejca.2003.10.016 14962714
     [Google Scholar]
  14. Al-RawiM A A. RmaliK. ManselR.E. JiangW.G. Interleukin 7 induces the growth of breast cancer cells through a wortmannin-sensitive pathway.Br. J. Surg.2003911616810.1002/bjs.4449 14716795
     [Google Scholar]
  15. ShiL. XuZ. YangQ. HuangY. GongY. WangF. KeB. IL‐7–Mediated IL‐7R‐JAK3/STAT5 signalling pathway contributes to chemotherapeutic sensitivity in non–small‐cell lung cancer.Cell Prolif.2019526e1269910.1111/cpr.12699 31599032
     [Google Scholar]
  16. HeoS.H. JangS.I. KimS.Y. ChoiB. LeeD.K. LeeH.K. ChangE.J. Characterization of circulating il-7r positive cell populations for early detection of pancreatic ductal adenocarcinoma.J. Clin. Med.20211018415710.3390/jcm10184157 34575268
     [Google Scholar]
  17. QuH. ZouZ. PanZ. ZhangT. DengN. ChenG. WangZ. IL-7/IL-7 receptor axis stimulates prostate cancer cell invasion and migration via AKT/NF-κB pathway.Int. Immunopharmacol.20164020321010.1016/j.intimp.2016.08.017 27611862
     [Google Scholar]
  18. VerdelliC. VairaV. CorbettaS. Parathyroid tumor microenvironment.Adv. Exp. Med. Biol.20201226375010.1007/978‑3‑030‑36214‑0_3 32030674
     [Google Scholar]
  19. HouthuijzenJ.M. JonkersJ. Cancer-associated fibroblasts as key regulators of the breast cancer tumor microenvironment.Cancer Metastasis Rev.201837457759710.1007/s10555‑018‑9768‑3 30465162
     [Google Scholar]
  20. BelliC. TrapaniD. VialeG. D’AmicoP. DusoB.A. VignaD.P. OrsiF. CuriglianoG. Targeting the microenvironment in solid tumors.Cancer Treat. Rev.201865223210.1016/j.ctrv.2018.02.004 29502037
     [Google Scholar]
  21. RodriguesR.C. MendesR. BaptistaP. FernandesA. Targeting tumor microenvironment for cancer therapy.Int. J. Mol. Sci.201920484010.3390/ijms20040840 30781344
     [Google Scholar]
  22. BarataJ.T. DurumS.K. SeddonB. Flip the coin: IL-7 and IL-7R in health and disease.Nat. Immunol.201920121584159310.1038/s41590‑019‑0479‑x 31745336
     [Google Scholar]
  23. LinJ. ZhuZ. XiaoH. WakefieldM.R. DingV.A. BaiQ. FangY. The role of il-7 in immunity and cancer.Anticancer Res.201737396396810.21873/anticanres.11405 28314253
     [Google Scholar]
  24. KulkarniU. HerrmenauC. WinS.J. BauerM. KamradtT. IL-7 treatment augments and prolongs sepsis-induced expansion of IL-10-producing B lymphocytes and myeloid-derived suppressor cells.PLoS One2018132e019230410.1371/journal.pone.0192304 29466409
     [Google Scholar]
  25. MelchiondaF. FryT.J. MillironM.J. McKirdyM.A. TagayaY. MackallC.L. Adjuvant IL-7 or IL-15 overcomes immunodominance and improves survival of the CD8+ memory cell pool.J. Clin. Invest.200511551177118710.1172/JCI200523134 15841203
     [Google Scholar]
  26. BradleyL.M. HaynesL. SwainS.L. IL-7: Maintaining T-cell memory and achieving homeostasis.Trends Immunol.200526317217610.1016/j.it.2005.01.004 15745860
     [Google Scholar]
  27. SwainsonL. KinetS. MongellazC. SourisseauM. HenriquesT. TaylorN. IL-7–induced proliferation of recent thymic emigrants requires activation of the PI3K pathway.Blood200710931034104210.1182/blood‑2006‑06‑027912 17023582
     [Google Scholar]
  28. KittipatarinC. KhaledA.R. Interlinking interleukin-7.Cytokine2007391758310.1016/j.cyto.2007.07.183 17768066
     [Google Scholar]
  29. LiB. VanRoeyM.J. JoossK. Recombinant IL-7 enhances the potency of GM-CSF-secreting tumor cell immunotherapy.Clin. Immunol.2007123215516510.1016/j.clim.2007.01.002 17320482
     [Google Scholar]
  30. HuangJ. LongZ. JiaR. WangM. ZhuD. LiuM. ChenS. ZhaoX. YangQ. WuY. ZhangS. TianB. MaoS. OuX. SunD. GaoQ. ChengA. The broad immunomodulatory effects of il-7 and its application in vaccines.Front. Immunol.20211268044210.3389/fimmu.2021.680442 34956167
     [Google Scholar]
/content/journals/cchts/10.2174/0113862073293963240409040110
Loading
IL-7R Expression Correlates with Prognosis in Breast Cancer
Comb Chem High Throughput Screen 28, 973 (2025); https://doi.org/10.2174/0113862073293963240409040110
/content/journals/cchts/10.2174/0113862073293963240409040110
/content/journals/cchts/10.2174/0113862073293963240409040110
Loading

Data & Media loading...


  • Article Type:     Research Article
Keyword(s): breast cancer; IL-7R; immunity; prognostic indicator; TCGA; Tumor microenvironment

Most Cited Most Cited RSS feed

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