Development and Validation of Novel Prognostic Models Based on RNA-binding Proteins in Breast Cancer

Overview

Journal J Int Med Res

Publisher Sage Publications

Specialty General Medicine

Date 2022 Jun 30

PMID 35770997

Authors

Wei Fan

Jun Ding

Shushu Liu

Wei Zhong

Affiliations

Soon will be listed here.

Abstract

Objectives: We aimed to construct novel prognostic models based on RNA-binding proteins (RBPs) in breast cancer (BRCA) and explore their roles in this disease and their effects on tumor-infiltrating immune cells (TIICs).

Methods: Datasets were downloaded from the Gene Expression Omnibus (GEO) database. Functions and prognostic values of RBPs were systematically investigated using a series of bioinformatics analysis methods. TIICs were assessed using CIBERSORT.

Results: Overall, 138 differentially expressed RBPs were identified, of which 86 were upregulated and 52 were downregulated. Of these, 13 RBPs were identified as prognosis-related and adopted to construct an overall survival (OS) model, while 12 RBPs were used for the relapse-free survival (RFS) model. High-risk patients had poorer OS and RFS rates than low-risk patients. The results indicate that the OS and RFS models are good prognostic models with reliable predictive abilities. In addition, the proportions of CD8, CD4 naïve, and CD4 memory resting T cells, as well as resting dendritic cells, were significantly different between the low-risk and high-risk groups in the OS model.

Conclusions: OS and RFS signatures can be used as reliable BRCA prognostic biomarkers. This work will help understand the prognostic roles and functions of RBPs in BRCA.

References

Chin C, Chen S, Wu H, Ho C, Ko M, Lin C . cytoHubba: identifying hub objects and sub-networks from complex interactome. BMC Syst Biol. 2014; 8 Suppl 4:S11. PMC: 4290687. DOI: 10.1186/1752-0509-8-S4-S11. View

Barzaman K, Karami J, Zarei Z, Hosseinzadeh A, Kazemi M, Moradi-Kalbolandi S . Breast cancer: Biology, biomarkers, and treatments. Int Immunopharmacol. 2020; 84:106535. DOI: 10.1016/j.intimp.2020.106535. View

Yu G, Wang L, Han Y, He Q . clusterProfiler: an R package for comparing biological themes among gene clusters. OMICS. 2012; 16(5):284-7. PMC: 3339379. DOI: 10.1089/omi.2011.0118. View

Ritchie M, Phipson B, Wu D, Hu Y, Law C, Shi W . limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Res. 2015; 43(7):e47. PMC: 4402510. DOI: 10.1093/nar/gkv007. View

Anczukow O, Akerman M, Clery A, Wu J, Shen C, Shirole N . SRSF1-Regulated Alternative Splicing in Breast Cancer. Mol Cell. 2015; 60(1):105-17. PMC: 4597910. DOI: 10.1016/j.molcel.2015.09.005. View

Miles W, Lembo A, Volorio A, Brachtel E, Tian B, Sgroi D . Alternative Polyadenylation in Triple-Negative Breast Tumors Allows NRAS and c-JUN to Bypass PUMILIO Posttranscriptional Regulation. Cancer Res. 2016; 76(24):7231-7241. PMC: 5553310. DOI: 10.1158/0008-5472.CAN-16-0844. View

Wang J, Guo Y, Chu H, Guan Y, Bi J, Wang B . Multiple functions of the RNA-binding protein HuR in cancer progression, treatment responses and prognosis. Int J Mol Sci. 2013; 14(5):10015-41. PMC: 3676826. DOI: 10.3390/ijms140510015. View

Li J, Zhou W, Wei J, Xiao X, An T, Wu W . Prognostic Value and Biological Functions of RNA Binding Proteins in Stomach Adenocarcinoma. Onco Targets Ther. 2021; 14:1689-1705. PMC: 7942957. DOI: 10.2147/OTT.S297973. View

Heagerty P, Lumley T, Pepe M . Time-dependent ROC curves for censored survival data and a diagnostic marker. Biometrics. 2000; 56(2):337-44. DOI: 10.1111/j.0006-341x.2000.00337.x. View

10.

Elango R, Vishnubalaji R, Shaath H, Alajez N . Molecular subtyping and functional validation of TTK, TPX2, UBE2C, and LRP8 in sensitivity of TNBC to paclitaxel. Mol Ther Methods Clin Dev. 2021; 20:601-614. PMC: 7899947. DOI: 10.1016/j.omtm.2021.01.013. View

11.

He J, Chen Y, Cai L, Li Z, Guo X . UBAP2L silencing inhibits cell proliferation and G2/M phase transition in breast cancer. Breast Cancer. 2017; 25(2):224-232. PMC: 5818569. DOI: 10.1007/s12282-017-0820-x. View

12.

Masuda K, Kuwano Y . Diverse roles of RNA-binding proteins in cancer traits and their implications in gastrointestinal cancers. Wiley Interdiscip Rev RNA. 2018; 10(3):e1520. DOI: 10.1002/wrna.1520. View

13.

Alqahtani H, Gopal K, Gupta N, Jung K, AlShareef A, Ye X . DDX17 (P72), a Sox2 binding partner, promotes stem-like features conferred by Sox2 in a small cell population in estrogen receptor-positive breast cancer. Cell Signal. 2015; 28(2):42-50. DOI: 10.1016/j.cellsig.2015.11.004. View

14.

Liu H, Liu Y, Yang F, Zhang L, Zhang F, Hu X . Acetylation of MORC2 by NAT10 regulates cell-cycle checkpoint control and resistance to DNA-damaging chemotherapy and radiotherapy in breast cancer. Nucleic Acids Res. 2020; 48(7):3638-3656. PMC: 7144926. DOI: 10.1093/nar/gkaa130. View

15.

Lewinska A, Bednarz D, Adamczyk-Grochala J, Wnuk M . Phytochemical-induced nucleolar stress results in the inhibition of breast cancer cell proliferation. Redox Biol. 2017; 12:469-482. PMC: 5362140. DOI: 10.1016/j.redox.2017.03.014. View

16.

Hollern D, Xu N, Thennavan A, Glodowski C, Garcia-Recio S, Mott K . B Cells and T Follicular Helper Cells Mediate Response to Checkpoint Inhibitors in High Mutation Burden Mouse Models of Breast Cancer. Cell. 2019; 179(5):1191-1206.e21. PMC: 6911685. DOI: 10.1016/j.cell.2019.10.028. View

17.

Newman A, Liu C, Green M, Gentles A, Feng W, Xu Y . Robust enumeration of cell subsets from tissue expression profiles. Nat Methods. 2015; 12(5):453-7. PMC: 4739640. DOI: 10.1038/nmeth.3337. View

18.

Sung H, Ferlay J, Siegel R, Laversanne M, Soerjomataram I, Jemal A . Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021; 71(3):209-249. DOI: 10.3322/caac.21660. View

19.

Hao A, Wang Y, Zhang X, Li J, Li Y, Li D . Long non-coding antisense RNA HYOU1-AS is essential to human breast cancer development through competitive binding hnRNPA1 to promote HYOU1 expression. Biochim Biophys Acta Mol Cell Res. 2021; 1868(4):118951. DOI: 10.1016/j.bbamcr.2021.118951. View

20.

Gerstberger S, Hafner M, Tuschl T . A census of human RNA-binding proteins. Nat Rev Genet. 2014; 15(12):829-45. PMC: 11148870. DOI: 10.1038/nrg3813. View