Comprehensive Analysis of Transcriptomics and Genetic Alterations Identifies Potential Mechanisms Underlying Anthracycline Therapy Resistance in Breast Cancer

Liu, Zihao1,2; Gao, Jingbo1; Gu, Ran1; Shi, Yu1; Hu, Hong2; Liu, Jianlan3; Huang, Jiefeng2; Zhong, Caineng2; Zhou, Wenbin2; Yang, Yaping1; Gong, Chang1

2022-12-01

10.3390/biom12121834

BIOMOLECULES   Impact Factor & Quartile

2218-273X

Anthracycline is a mainstay of treatment for breast cancer patients because of its antitumor activity. However, anthracycline resistance is a critical barrier in treating breast cancer. Thus, it is of great importance to uncover the molecular mechanisms underlying anthracycline resistance in breast cancer. Herein, we integrated transcriptome data, genetic alterations data, and clinical data of The Cancer Genome Atlas (TCGA) to identify the molecular mechanisms involved in anthracycline resistance in breast cancer. Two hundred and four upregulated genes and 1376 downregulated genes were characterized between the anthracycline-sensitive and anthracycline-resistant groups. It was found that drug resistance-associated genes such as ABCB5, CYP1A1, and CYP4Z1 were significantly upregulated in the anthracycline-resistant group. The gene set enrichment analysis (GSEA) suggested that the P53 signaling pathway, DNA replication, cysteine, and methionine metabolism pathways were associated with anthracycline sensitivity. Somatic TP53 mutation was a common genetic abnormality observed in the anthracycline-sensitive group, while CDH1 mutation was presented in the anthracycline-resistant group. Immune infiltration patterns were extremely different between the anthracycline-sensitive and anthracycline-resistant groups. Immune-associated chemokines and cytokines, immune regulators, and human leukocyte antigen genes were significantly upregulated in the anthracycline-sensitive group. These results reveal potential molecular mechanisms associated with anthracycline resistance.

anthracycline resistance breast cancer

SCI

English

Others

Project of The Beijing Xisike Clinical Oncology Research Foundation["Y-Roche2019/2-0078","Y-pierrefabre202102-0107"] ; Technology Development Program of Guangdong Province[2021A0505030082] ; Project of The Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation[2020B1212060018] ; Sun Yat-Sen Memorial Hospital Cultivation Project for Clinical Research[SYS-Q-202004] ; Sun Yat-Sen Memorial Hospital Yat-Sen Scientific Research Launch Project[YXQH201920] ; Medical Science and Technology Research Fund of Guangdong Province[A2020391] ; Guangzhou Science and Technology Program[202102010272] ; Fundamental Research Funds for the Central Universities, Sun Yat-Sen University[2022005] ; Natural Science Foundation of China["81872139","82072907","82003311"]

Biochemistry & Molecular Biology

Biochemistry & Molecular Biology

WOS:000902310000001

MDPI

Web of Science

1.Sun Yat Sen Univ, Sun Yat Sen Mem Hosp, Breast Tumor Ctr, Guangzhou 510120, Peoples R China
2.Jinan Univ, Southern Univ Sci & Technol, Shenzhen Peoples Hosp, Dept Breast & Thyroid Surg,Clin Med Coll 2,Affili, Shenzhen 518020, Peoples R China
3.Jinan Univ, Southern Univ Sci & Technol, Shenzhen Peoples Hosp, Dept Pathol,Clin Med Coll 2,Affiliated Hosp 1, Shenzhen 518020, Peoples R China

Liu, Zihao,Gao, Jingbo,Gu, Ran,et al. Comprehensive Analysis of Transcriptomics and Genetic Alterations Identifies Potential Mechanisms Underlying Anthracycline Therapy Resistance in Breast Cancer[J]. BIOMOLECULES,2022,12(12).

Liu, Zihao.,Gao, Jingbo.,Gu, Ran.,Shi, Yu.,Hu, Hong.,...&Gong, Chang.(2022).Comprehensive Analysis of Transcriptomics and Genetic Alterations Identifies Potential Mechanisms Underlying Anthracycline Therapy Resistance in Breast Cancer.BIOMOLECULES,12(12).

Liu, Zihao,et al."Comprehensive Analysis of Transcriptomics and Genetic Alterations Identifies Potential Mechanisms Underlying Anthracycline Therapy Resistance in Breast Cancer".BIOMOLECULES 12.12(2022).