PDF (20 MB)
Collect
Submit Manuscript
Show Outline
Outline
Abstract
Keywords
References
Show full outline
Hide outline

Immunoprognostic Model Construction of m6A-Associated lncRNAs in Triple-Negative Breast Cancer

Shumei BAO1Haoqin GUAN2Ying SU2Pei LIU2Xiaoyi LYU1()
School of Software, Xinjiang University, Urumqi Xinjiang 830091, China
School of Information Science and Engineering, Xinjiang University, Urumqi Xinjiang 830017, China
Show Author Information

Abstract

Triple-negative breast cancer (TNBC) is a specific subtype of breast cancer. Because of its heterogeneity and the lack of reliable molecular targets for effective targeted therapy, the survival rate of TNBC patients remains low. N6-methyladenosine (m6A) and long-stranded non-coding ribonucleic acid (lncRNA) play a critical role in the prognostic value and immunotherapeutic response of TNBC. Therefore, it is important to identify m6A-associated lncRNAs in TNBC patients. In this study, m6A-associated lncRNAs were analyzed and obtained by co-expression. Univariate Cox, random survival forest (RSF), least absolute shrinkage and selection operator (LASSO) and multivariate Cox regression analyses were then performed to construct m6A-associated lncRNA models. Kaplan-Meier (KM) survival analysis, principal component analysis (PCA), functional enrichment analysis, and column line plots were then used to analyze the risk models. Finally, potential immunotherapy profiles and drug sensitivity predictions for the model were also discussed. A risk model containing 3 m6A-associated lncRNAs was identified as an independent predictor of prognosis. By regrouping patients using this model, we can differentiate patients more effectively in terms of their response to immunotherapy. Drug candidates targeting TNBC subtype differentiation were identified using the pRRhetic algorithm to estimate treatment response based on the half-maximal inhibitory concentration (IC50) available in the Genomics of Drug Sensitivity in Cancer (GDSC) database for each sample. The findings suggest that this m6A-based lncRNA risk model may be promising for clinical prediction of prognosis and immunotherapy response in TNBC patients.

Article ID: 2096-7675(2024)01-0078-09

References

[1]
SUNG H, FERLAY J, SIEGEL R L, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA: a Cancer Journal for Clinicians, 2021, 71(3): 209-249.
[2]
CAO L, NIU Y. Triple negative breast cancer: Special histological types and emerging therapeutic methods[J]. Cancer Biology & Medicine, 2020, 17(2): 293-306.
[3]
QIU J D, XUE X Y, HU C, et al. Comparison of clinicopathological features and prognosis in triple-negative and non-triple negative breast cancer[J]. Journal of Cancer, 2016, 7(2): 167-173.
[4]
BONOTTO M, GERRATANA L, POLETTO E, et al. Measures of outcome in metastatic breast cancer: Insights from a real-world scenario[J]. The Oncologist, 2014, 19(6): 608-615.
[5]
SCHMADEKA R, HARMON B E, SINGH M. Triple-negative breast carcinoma: Current and emerging concepts[J]. American Journal of Clinical Pathology, 2014, 141(4): 462-477.
[6]
MILLIS S Z, GATALICA Z, WINKLER J, et al. Predictive biomarker profiling of>6 000 breast cancer patients shows heterogeneity in TNBC, with treatment implications[J]. Clinical Breast Cancer, 2015, 15(6): 473-481. e3.
[7]
CRAIG D W, O'SHAUGHNESSY J A, KIEFER J A, et al. Genome and transcriptome sequencing in prospective metastatic triple-negative breast cancer uncovers therapeutic vulnerabilities[J]. Molecular Cancer Therapeutics, 2013, 12(1): 104-116.
[8]
SUN T, WU R Y, MING L. The role of m6A RNA methylation in cancer[J]. Biomedicine & Pharmacotherapy, 2019, 112: 108613.
[9]
LIU Z X, LI L M, SUN H L, et al. Link between m6A modification and cancers[J]. Frontiers in Bioengineering and Biotechnology, 2018, 6: 89.
[10]
TU Z W, WU L, WANG P, et al. N6-methylandenosine-related lncRNAs are potential biomarkers for predicting the overall survival of lower-grade glioma patients[J]. Frontiers in Cell and Developmental Biology, 2020, 8: 642.
[11]
ZHOU K I, PARISIEN M, DAI Q, et al. N6-methyladenosine modification in a long noncoding RNA hairpin predisposes its conformation to protein binding[J]. Journal of Molecular Biology, 2016, 428(5 Pt A): 822-833.
[12]
SHI Y, ZHENG C L, JIN Y, et al. Reduced expression of METTL3 promotes metastasis of triple-negative breast cancer by m6A methylation-mediated COL3A1 up-regulation[J]. Frontiers in Oncology, 2020, 10: 1126.
[13]
LIN Y X, JIN X, NIE Q, et al. YTHDF3 facilitates triple-negative breast cancer progression and metastasis by stabilizing ZEB1 mRNA in an m6 A-dependent manner[J]. Annals of Translational Medicine, 2022, 10(2): 83.
[14]
WANG S S, ZOU X, CHEN Y J, et al. Effect of N6-methyladenosine regulators on progression and prognosis of triple-negative breast cancer[J]. Frontiers in Genetics, 2021, 11: 580036.
[15]
WU J, CAI Y, ZHAO G P, et al. A ten N6-methyladenosine-related long non-coding RNAs signature predicts prognosis of triple-negative breast cancer[J]. Journal of Clinical Laboratory Analysis, 2021, 35(6): e23779.
[16]
HONG W F, LIANG L, GU Y J, et al. Immune-related lncRNA to construct novel signature and predict the immune landscape of human hepatocellular carcinoma[J]. Molecular Therapy: Nucleic Acids, 2020, 22: 937-947.
[17]
ZHU J F, HUANG Q, PENG X Y, et al. Identification of molecular subtypes based on PANoptosis-related genes and construction of a signature for predicting the prognosis and response to immunotherapy response in hepatocellular carcinoma[J]. Frontiers in Immunology, 2023, 14: 1218661.
[18]
ZHAO X Y, LIU X W, CUI L. Development of a five-protein signature for predicting the prognosis of head and neck squamous cell carcinoma[J]. Aging, 2020, 12(19): 19740-19755.
[19]
WU Z L, WANG M R, LIU Q G, et al. Identification of gene expression profiles and immune cell infiltration signatures between low and high tumor mutation burden groups in bladder cancer[J]. International Journal of Medical Sciences, 2020, 17(1): 89-96.
[20]
XU F, ZHAN X Q, ZHENG X H, et al. A signature of immune-related gene pairs predicts oncologic outcomes and response to immunotherapy in lung adenocarcinoma[J]. Genomics, 2020, 112(6): 4675-4683.
[21]
LI X Y, LI Y, YU X M, et al. Identification and validation of stemness-related lncRNA prognostic signature for breast cancer[J]. Journal of Translational Medicine, 2020, 18(1): 331.
[22]
ISHWARAN H, KOGALUR U B, BLACKSTONE E H, et al. Random survival forests[J]. The Annals of Applied Statistics, 2008, 2(3): 841-860.
[23]
SONG J, ZHANG W F, WANG S, et al. A panel of 7 prognosis-related long non-coding RNAs to improve platinum-based chemoresistance prediction in ovarian cancer[J]. International Journal of Oncology, 2018, 53(2): 866-876.
[24]
ALLGÄUER M, BUDCZIES J, CHRISTOPOULOS P, et al. Implementing tumor mutational burden (TMB) analysis in routine diagnostics: A primer for molecular pathologists and clinicians[J]. Translational Lung Cancer Research, 2018, 7(6): 703-715.
[25]
TOPALIAN S L, TAUBE J M, ANDERS R A, et al. Mechanism-driven biomarkers to guide immune checkpoint blockade in cancer therapy[J]. Nature Reviews Cancer, 2016, 16: 275-287.
[26]
JIANG P, GU S Q, PAN D, et al. Signatures of T cell dysfunction and exclusion predict cancer immunotherapy response[J]. Nature Medicine, 2018, 24: 1550-1558.
[27]
BORRI F, GRANAGLIA A. Pathology of triple negative breast cancer[J]. Seminars in Cancer Biology, 2021, 72: 136-145.
[28]
SHARMA P, BARLOW W E, GODWIN A K, et al. Impact of homologous recombination deficiency biomarkers on outcomes in patients with triple-negative breast cancer treated with adjuvant doxorubicin and cyclophosphamide (SWOG S9313)[J]. Annals of Oncology: Official Journal of the European Society for Medical Oncology, 2018, 29(3): 654-660.
Journal of Xinjiang University(Natural Science Edition in Chinese and English)
Pages 78-86
Cite this article:
BAO S, GUAN H, SU Y, et al. Immunoprognostic Model Construction of m6A-Associated lncRNAs in Triple-Negative Breast Cancer. Journal of Xinjiang University(Natural Science Edition in Chinese and English), 2024, 41(1): 78-86. https://doi.org/10.13568/j.cnki.651094.651316.2023.03.17.0001
Metrics & Citations  
Article History
Copyright
Return