Analysis of the Potential Biological Significance of Glycosylation in Triple-negative Breast Cancer on Patient Prognosis

Overview

Journal Am J Transl Res

Specialty General Medicine

Date 2024 Jul 15

PMID 39006258

Authors

Han Zhou

Zhiwei Wang

Jun Guo

Zihui Zhu

Gang Sun

Affiliations

Soon will be listed here.

Abstract

Background: Breast cancer is the most common malignancy in women, with its prognosis varying greatly according to its subtype. Triple-negative breast cancer (TNBC) has the worst prognosis among all subtypes. Glycosylation is a critical factor influencing the prognosis of patients with TNBC. Our aim is to develop a tumor prognosis model by analyzing genes related to glycosylation to predict patient outcomes.

Methods: The dataset used in this study was downloaded from the Cancer Genome Atlas Program (TCGA) database, and predictive genes were identified through Cox one-way regression analysis. The model genes with the highest risk scores among the 18 samples were obtained by lasso regression analysis to establish the model. We analyzed the pathways affecting the progression of TNBC and discovered key genes for subsequent research.

Results: Our model was constructed using data from TCGA database and validated through Kaplan-Meier curve analysis and Receiver Operating Characteristic (ROC) curve assessment. Our analysis revealed that a high expression of tumor-related chemokines in the high-risk group may be associated with poor tumor prognosis. Furthermore, we conducted a random survival forest analysis and identified two significant genes, namely DPM2 and PINK1, which have been selected for further investigation.

Conclusion: The prognostic analysis model, developed based on the glycosylation genes in TNBC, exhibits excellent validation efficacy. This model is valuable for the prognostic analysis of patients with TNBC.

References

Li Y, Zhang H, Merkher Y, Chen L, Liu N, Leonov S . Recent advances in therapeutic strategies for triple-negative breast cancer. J Hematol Oncol. 2022; 15(1):121. PMC: 9422136. DOI: 10.1186/s13045-022-01341-0. View

Korbecki J, Kojder K, Siminska D, Bohatyrewicz R, Gutowska I, Chlubek D . CC Chemokines in a Tumor: A Review of Pro-Cancer and Anti-Cancer Properties of the Ligands of Receptors CCR1, CCR2, CCR3, and CCR4. Int J Mol Sci. 2020; 21(21). PMC: 7665155. DOI: 10.3390/ijms21218412. View

Ferrari P, Scatena C, Ghilli M, Bargagna I, Lorenzini G, Nicolini A . Molecular Mechanisms, Biomarkers and Emerging Therapies for Chemotherapy Resistant TNBC. Int J Mol Sci. 2022; 23(3). PMC: 8836182. DOI: 10.3390/ijms23031665. View

Chen M, Wang S . Preclinical development and clinical studies of targeted JAK/STAT combined Anti-PD-1/PD-L1 therapy. Int Immunopharmacol. 2024; 130:111717. DOI: 10.1016/j.intimp.2024.111717. View

Kaur A, Baldwin J, Brar D, Salunke D, Petrovsky N . Toll-like receptor (TLR) agonists as a driving force behind next-generation vaccine adjuvants and cancer therapeutics. Curr Opin Chem Biol. 2022; 70:102172. DOI: 10.1016/j.cbpa.2022.102172. View

Christiansen M, Chik J, Lee L, Anugraham M, Abrahams J, Packer N . Cell surface protein glycosylation in cancer. Proteomics. 2013; 14(4-5):525-46. DOI: 10.1002/pmic.201300387. View

Yudintceva N, Bobkov D, Sulatsky M, Mikhailova N, Oganesyan E, Vinogradova T . Mesenchymal stem cells-derived extracellular vesicles for therapeutics of renal tuberculosis. Sci Rep. 2024; 14(1):4495. PMC: 10894196. DOI: 10.1038/s41598-024-54992-z. View

Song M, Park J, Park S, Lee D, Choi H, Park B . NSC-87877, inhibitor of SHP-1/2 PTPs, inhibits dual-specificity phosphatase 26 (DUSP26). Biochem Biophys Res Commun. 2009; 381(4):491-5. DOI: 10.1016/j.bbrc.2009.02.069. View

Leonard J, Trneny M, Izutsu K, Fowler N, Hong X, Zhu J . AUGMENT: A Phase III Study of Lenalidomide Plus Rituximab Versus Placebo Plus Rituximab in Relapsed or Refractory Indolent Lymphoma. J Clin Oncol. 2019; 37(14):1188-1199. PMC: 7035866. DOI: 10.1200/JCO.19.00010. View

10.

Liubomirski Y, Lerrer S, Meshel T, Rubinstein-Achiasaf L, Morein D, Wiemann S . Tumor-Stroma-Inflammation Networks Promote Pro-metastatic Chemokines and Aggressiveness Characteristics in Triple-Negative Breast Cancer. Front Immunol. 2019; 10:757. PMC: 6473166. DOI: 10.3389/fimmu.2019.00757. View

11.

Kaur P, Nagar S, Bhagwat M, Uddin M, Zhu Y, Vancurova I . Activated heme synthesis regulates glycolysis and oxidative metabolism in breast and ovarian cancer cells. PLoS One. 2021; 16(11):e0260400. PMC: 8608300. DOI: 10.1371/journal.pone.0260400. View

12.

Scott D, Drake R . Glycosylation and its implications in breast cancer. Expert Rev Proteomics. 2019; 16(8):665-680. PMC: 6702063. DOI: 10.1080/14789450.2019.1645604. View

13.

Garrido-Castro A, Lin N, Polyak K . Insights into Molecular Classifications of Triple-Negative Breast Cancer: Improving Patient Selection for Treatment. Cancer Discov. 2019; 9(2):176-198. PMC: 6387871. DOI: 10.1158/2159-8290.CD-18-1177. View

14.

Hao Ing Y, Md Salleh M, Yahya M, Ankathil R, Abdul Aziz A . Association of ABCG2 Polymorphisms on Triple Negative Breast Cancer (TNBC) Susceptibility Risk. Asian Pac J Cancer Prev. 2023; 24(11):3891-3897. PMC: 10772757. DOI: 10.31557/APJCP.2023.24.11.3891. View

15.

Kane L, Lazarou M, Fogel A, Li Y, Yamano K, Sarraf S . PINK1 phosphorylates ubiquitin to activate Parkin E3 ubiquitin ligase activity. J Cell Biol. 2014; 205(2):143-53. PMC: 4003245. DOI: 10.1083/jcb.201402104. View

16.

Zhou R, Yazdanifar M, Das Roy L, Whilding L, Gavrill A, Maher J . Corrigendum: CAR T Cells Targeting the Tumor MUC1 Glycoprotein Reduce Triple-Negative Breast Cancer Growth. Front Immunol. 2020; 11:628776. PMC: 7750685. DOI: 10.3389/fimmu.2020.628776. View

17.

Han X, Chen J, Wang J, Xu J, Liu Y . TTN mutations predict a poor prognosis in patients with thyroid cancer. Biosci Rep. 2022; 42(7). PMC: 9310696. DOI: 10.1042/BSR20221168. View

18.

Li Q, Chu Y, Li S, Yu L, Deng H, Liao C . The oncoprotein MUC1 facilitates breast cancer progression by promoting Pink1-dependent mitophagy via ATAD3A destabilization. Cell Death Dis. 2022; 13(10):899. PMC: 9606306. DOI: 10.1038/s41419-022-05345-z. View

19.

Lutz V, Hellmund V, Picard F, Raifer H, Ruckenbrod T, Klein M . IL18 Receptor Signaling Regulates Tumor-Reactive CD8+ T-cell Exhaustion via Activation of the IL2/STAT5/mTOR Pathway in a Pancreatic Cancer Model. Cancer Immunol Res. 2023; 11(4):421-434. DOI: 10.1158/2326-6066.CIR-22-0398. View

20.

Ritter V, Krautter F, Klein D, Jendrossek V, Rudner J . Bcl-2/Bcl-xL inhibitor ABT-263 overcomes hypoxia-driven radioresistence and improves radiotherapy. Cell Death Dis. 2021; 12(7):694. PMC: 8277842. DOI: 10.1038/s41419-021-03971-7. View