A Risk Model of 10 Aging-related Genes for Predicting Survival and Immune Response in Triple-negative Breast Cancer

Overview

Journal Cancer Med

Specialty Oncology

Date 2022 Mar 17

PMID 35297220

Authors

Xia Yang

Yanhua Sun

Xia Liu

Zhinong Jiang

Affiliations

Soon will be listed here.

Abstract

Accumulated studies showed that the clinical significance of aging on the development and malignancy of tumors, while the relationship between aging and the prognosis, immune response in triple-negative breast cancer (TNBC) has not been well clarified. Here, we constructed a risk model of 10 prognostic aging-related genes (ARGs) from METABRIC database. Then, TNBC patients were classified into high- and low-risk groups, the survival diversity, immune response, genomic function, and tumor mutation burden (TMB) between different risk groups were explored in METABRIC, TCGA, and GSE58812 cohorts. Results showed that patients in the high-risk group had poorer survival outcomes compared to their counterparts (all p < 0.05), and the nomogram we established showed reliable prediction ability for survival in TNBC patients. Besides, TNBC patients with high-risk scores had a lower expression of immune checkpoint markers and a lower fraction of activated immune cells. Furthermore, GSEA showed that Notch signaling pathway was significantly enriched in the high-risk group. Thus, a risk model based on the aging-related genes was developed and validated in this study, which may serve as a potential biomarker for prognosis and personalized treatment in TNBCs.

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References

Kaiser M, Semeraro M, Herrmann M, Absenger G, Gerger A, Renner W . Immune Aging and Immunotherapy in Cancer. Int J Mol Sci. 2021; 22(13). PMC: 8269421. DOI: 10.3390/ijms22137016. View

Faget D, Ren Q, Stewart S . Unmasking senescence: context-dependent effects of SASP in cancer. Nat Rev Cancer. 2019; 19(8):439-453. DOI: 10.1038/s41568-019-0156-2. View

Mayakonda A, Lin D, Assenov Y, Plass C, Koeffler H . Maftools: efficient and comprehensive analysis of somatic variants in cancer. Genome Res. 2018; 28(11):1747-1756. PMC: 6211645. DOI: 10.1101/gr.239244.118. View

Lee E, Choi A, Jun Y, Kim N, In Yook J, Kim S . Glutathione peroxidase-1 regulates adhesion and metastasis of triple-negative breast cancer cells via FAK signaling. Redox Biol. 2020; 29:101391. PMC: 6906704. DOI: 10.1016/j.redox.2019.101391. View

Zhang Z, Kattan M . Drawing Nomograms with R: applications to categorical outcome and survival data. Ann Transl Med. 2017; 5(10):211. PMC: 5451623. DOI: 10.21037/atm.2017.04.01. View

Karn T, Denkert C, Weber K, Holtrich U, Hanusch C, Sinn B . Tumor mutational burden and immune infiltration as independent predictors of response to neoadjuvant immune checkpoint inhibition in early TNBC in GeparNuevo. Ann Oncol. 2020; 31(9):1216-1222. DOI: 10.1016/j.annonc.2020.05.015. View

He Q, Au B, Kulkarni M, Shen Y, Lim K, Maimaiti J . Chromosomal instability-induced senescence potentiates cell non-autonomous tumourigenic effects. Oncogenesis. 2018; 7(8):62. PMC: 6092349. DOI: 10.1038/s41389-018-0072-4. View

Nolan E, Savas P, Policheni A, Darcy P, Vaillant F, Mintoff C . Combined immune checkpoint blockade as a therapeutic strategy for -mutated breast cancer. Sci Transl Med. 2017; 9(393). PMC: 5822709. DOI: 10.1126/scitranslmed.aal4922. View

Zhang M, Zhang X, Zhao S, Wang Y, Di W, Zhao G . Prognostic value of survivin and EGFR protein expression in triple-negative breast cancer (TNBC) patients. Target Oncol. 2013; 9(4):349-57. DOI: 10.1007/s11523-013-0300-y. View

10.

Reinhold W, Sunshine M, Liu H, Varma S, Kohn K, Morris J . CellMiner: a web-based suite of genomic and pharmacologic tools to explore transcript and drug patterns in the NCI-60 cell line set. Cancer Res. 2012; 72(14):3499-511. PMC: 3399763. DOI: 10.1158/0008-5472.CAN-12-1370. View

11.

Tibshirani R . The lasso method for variable selection in the Cox model. Stat Med. 1997; 16(4):385-95. DOI: 10.1002/(sici)1097-0258(19970228)16:4<385::aid-sim380>3.0.co;2-3. View

12.

Di Mauro C, Rosa R, Damato V, Ciciola P, Servetto A, Marciano R . Hedgehog signalling pathway orchestrates angiogenesis in triple-negative breast cancers. Br J Cancer. 2017; 116(11):1425-1435. PMC: 5520095. DOI: 10.1038/bjc.2017.116. View

13.

Shanley D, Aw D, Manley N, Palmer D . An evolutionary perspective on the mechanisms of immunosenescence. Trends Immunol. 2009; 30(7):374-81. DOI: 10.1016/j.it.2009.05.001. View

14.

Balducci L, Ershler W . Cancer and ageing: a nexus at several levels. Nat Rev Cancer. 2005; 5(8):655-62. DOI: 10.1038/nrc1675. View

15.

Savas P, Loi S . Expanding the Role for Immunotherapy in Triple-Negative Breast Cancer. Cancer Cell. 2020; 37(5):623-624. DOI: 10.1016/j.ccell.2020.04.007. View

16.

Coppe J, Desprez P, Krtolica A, Campisi J . The senescence-associated secretory phenotype: the dark side of tumor suppression. Annu Rev Pathol. 2010; 5:99-118. PMC: 4166495. DOI: 10.1146/annurev-pathol-121808-102144. View

17.

Hughes K, Alipaz J, M Drnevich J, Reynolds R . A test of evolutionary theories of aging. Proc Natl Acad Sci U S A. 2002; 99(22):14286-91. PMC: 137876. DOI: 10.1073/pnas.222326199. View

18.

Elias R, Hartshorn K, Rahma O, Lin N, Snyder-Cappione J . Aging, immune senescence, and immunotherapy: A comprehensive review. Semin Oncol. 2018; 45(4):187-200. DOI: 10.1053/j.seminoncol.2018.08.006. View

19.

Gao C, Li H, Liu C, Xu X, Zhuang J, Zhou C . Tumor Mutation Burden and Immune Invasion Characteristics in Triple Negative Breast Cancer: Genome High-Throughput Data Analysis. Front Immunol. 2021; 12:650491. PMC: 8097167. DOI: 10.3389/fimmu.2021.650491. View

20.

Lopez-Otin C, Blasco M, Partridge L, Serrano M, Kroemer G . The hallmarks of aging. Cell. 2013; 153(6):1194-217. PMC: 3836174. DOI: 10.1016/j.cell.2013.05.039. View