Identification of SLC31A1 As a Prognostic Biomarker and a Target for Therapeutics in Breast Cancer

Overview

Journal Sci Rep

Specialty Science

Date 2024 Oct 25

PMID 39448672

Authors

Hongtao Fu

Shanshan Dong

Kun Li

Affiliations

Soon will be listed here.

Abstract

Copper-induced cell death is regulated through protein lipoylation, which is critical for gene expression and phenotypic regulation. Neverless, the role of Cuproptosis-related genes in breast cancer (BC) remains unknown. This study aimed to construct a prognostic signature based on the expression of Cuproptosis-related genes in order to guide the diagnosis and treatment for BC. Cuproptosis-related genes prognostic signature has ata of 1250 BC tissues and 583 normal breast tissues were obtained from The Cancer Genome Atlas (TCGA), Genotype Tissue Expression (GTEx), and GEO GSE65212. The prognostic signature was established and evaluated with nineteen Cuproptosis-related genes. A series of in silico analyses based on SLC31A1, included expression analysis, independent prognostic analysis, correlation analysis, immune-related analysis and survival analysis. Finally, a series of cell experiments (including quantitative real-time polymerase chain reaction and western blot), and mice experiments were applied to evaluate the impact of SLC31A1 on BC. Cuproptosis-related genes prognostic signature has good predictive promising for survival in BC patients. We discovered that SLC31A1SLC31A1 was overexpressed in BC and was its independent prognostic factor. High expression of the SLC31A1 was correlated with poor prognosis and immune infiltrating of BC. SLC31A1 expression is associated with immune, chemotherapeutic and targeted therapy outcomes in BC. The proliferation, migration, and invasiveness of Her2 + enriched BC cells were decreased by SLC31A1 knockdown, also resulting in a decrease in tumor volume in mouse model. SLC31A1 is a candidate biomarker or therapeutic target in precision oncology, with diagnostic and prognostic significance in BC.

References

Lotfi R, Lotze M . Eosinophils induce DC maturation, regulating immunity. J Leukoc Biol. 2007; 83(3):456-60. DOI: 10.1189/jlb.0607366. View

Yu T, Yu S, Lu K . Comprehensive Molecular Analyses of an SLC Family-Based Model in Stomach Adenocarcinoma. Pathol Oncol Res. 2022; 28:1610610. PMC: 9606230. DOI: 10.3389/pore.2022.1610610. View

Barkal A, Brewer R, Markovic M, Kowarsky M, Barkal S, Zaro B . CD24 signalling through macrophage Siglec-10 is a target for cancer immunotherapy. Nature. 2019; 572(7769):392-396. PMC: 6697206. DOI: 10.1038/s41586-019-1456-0. View

Li L, Piontek K, Ishida M, Fausther M, Dranoff J, Fu R . Extracellular vesicles carry microRNA-195 to intrahepatic cholangiocarcinoma and improve survival in a rat model. Hepatology. 2016; 65(2):501-514. PMC: 5258762. DOI: 10.1002/hep.28735. View

Liu P, Brown S, Goktug T, Channathodiyil P, Kannappan V, Hugnot J . Cytotoxic effect of disulfiram/copper on human glioblastoma cell lines and ALDH-positive cancer-stem-like cells. Br J Cancer. 2012; 107(9):1488-97. PMC: 3493777. DOI: 10.1038/bjc.2012.442. View

Hu B, Wang Q, Wang Y, Hua S, Gabriel Sauve C, Ong D . Epigenetic Activation of WNT5A Drives Glioblastoma Stem Cell Differentiation and Invasive Growth. Cell. 2016; 167(5):1281-1295.e18. PMC: 5320931. DOI: 10.1016/j.cell.2016.10.039. View

Park J, Park J, Jun Y, Oh Y, Ryoo G, Jeong Y . Expanding therapeutic utility of carfilzomib for breast cancer therapy by novel albumin-coated nanocrystal formulation. J Control Release. 2019; 302:148-159. PMC: 6638563. DOI: 10.1016/j.jconrel.2019.04.006. View

Fu J, Li K, Zhang W, Wan C, Zhang J, Jiang P . Large-scale public data reuse to model immunotherapy response and resistance. Genome Med. 2020; 12(1):21. PMC: 7045518. DOI: 10.1186/s13073-020-0721-z. View

Lou W, Ding B, Wang J, Xu Y . The Involvement of the hsa_circ_0088494-miR-876-3p-CTNNB1/CCND1 Axis in Carcinogenesis and Progression of Papillary Thyroid Carcinoma. Front Cell Dev Biol. 2020; 8:605940. PMC: 7755655. DOI: 10.3389/fcell.2020.605940. View

10.

Cai C, Huo Q, Wang X, Chen B, Yang Q . SNHG16 contributes to breast cancer cell migration by competitively binding miR-98 with E2F5. Biochem Biophys Res Commun. 2017; 485(2):272-278. DOI: 10.1016/j.bbrc.2017.02.094. View

11.

Ghafouri-Fard S, Shoorei H, Tondro Anamag F, Taheri M . The Role of Non-Coding RNAs in Controlling Cell Cycle Related Proteins in Cancer Cells. Front Oncol. 2020; 10:608975. PMC: 7734207. DOI: 10.3389/fonc.2020.608975. View

12.

Koch K, Pena M, Thiele D . Copper-binding motifs in catalysis, transport, detoxification and signaling. Chem Biol. 1997; 4(8):549-60. DOI: 10.1016/s1074-5521(97)90241-6. View

13.

Liu L, Yang J, Wang C . Analysis of the prognostic significance of solute carrier (SLC) family 39 genes in breast cancer. Biosci Rep. 2020; 40(8). PMC: 7426635. DOI: 10.1042/BSR20200764. View

14.

Saraiva D, Jacinto A, Borralho P, Braga S, Cabral M . HLA-DR in Cytotoxic T Lymphocytes Predicts Breast Cancer Patients' Response to Neoadjuvant Chemotherapy. Front Immunol. 2018; 9:2605. PMC: 6282034. DOI: 10.3389/fimmu.2018.02605. View

15.

Waddington D, Boele T, Maschmeyer R, Kuncic Z, Rosen M . High-sensitivity in vivo contrast for ultra-low field magnetic resonance imaging using superparamagnetic iron oxide nanoparticles. Sci Adv. 2020; 6(29):eabb0998. PMC: 7367688. DOI: 10.1126/sciadv.abb0998. View

16.

Reynolds L, Howard T, Ruczinski I, Kanchan K, Seeds M, Mathias R . Tissue-specific impact of FADS cluster variants on FADS1 and FADS2 gene expression. PLoS One. 2018; 13(3):e0194610. PMC: 5874031. DOI: 10.1371/journal.pone.0194610. View

17.

Cai M, Liang X, Sun X, Chen H, Dong Y, Wu L . Nuclear Receptor Coactivator 2 Promotes Human Breast Cancer Cell Growth by Positively Regulating the MAPK/ERK Pathway. Front Oncol. 2019; 9:164. PMC: 6434718. DOI: 10.3389/fonc.2019.00164. View

18.

Makuku R, Khalili N, Razi S, Keshavarz-Fathi M, Rezaei N . Current and Future Perspectives of PD-1/PDL-1 Blockade in Cancer Immunotherapy. J Immunol Res. 2021; 2021:6661406. PMC: 7925068. DOI: 10.1155/2021/6661406. View

19.

de Faria Lainetti P, Leis-Filho A, Laufer-Amorim R, Battazza A, Fonseca-Alves C . Mechanisms of Resistance to Chemotherapy in Breast Cancer and Possible Targets in Drug Delivery Systems. Pharmaceutics. 2020; 12(12). PMC: 7763855. DOI: 10.3390/pharmaceutics12121193. View

20.

Shi Y, Zhang D, Liu J, Yang X, Xin R, Jia C . Comprehensive analysis to identify DLEU2L/TAOK1 axis as a prognostic biomarker in hepatocellular carcinoma. Mol Ther Nucleic Acids. 2021; 23:702-718. PMC: 7851426. DOI: 10.1016/j.omtn.2020.12.016. View