Comprehensive Analysis of Transcriptomics and Genetic Alterations Identifies Potential Mechanisms Underlying Anthracycline Therapy Resistance in Breast Cancer.
Comprehensive Analysis of Transcriptomics and Genetic Alterations Identifies Potential Mechanisms Underlying Anthracycline Therapy Resistance in Breast Cancer.
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转录组学和基因改变的综合分析确定了乳腺癌蒽环类药物耐药性的潜在机制
DOI：
10.3390/biom12121834
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发表时间：
2022-12-08
期刊：
影响因子：
5.5
通讯作者：
中科院分区：
文献类型：
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作者：
由于其抗肿瘤活性，蒽环类药物是乳腺癌患者的主要治疗药物。然而，对蒽环类药物的耐药性是治疗乳腺癌的关键障碍。因此，揭示乳腺癌对蒽环类药物耐药的分子机制具有重要意义。在这里，我们整合了转录组数据、基因改变数据和癌症基因组图谱(TCGA)的临床数据，以确定乳腺癌中参与蒽环类药物耐药的分子机制。在蒽环类药物敏感和耐药组中，共有204个基因表达上调，1376个基因表达下调。研究发现，耐药组中ABCB5、CYP1A1和CYP4Z1等耐药相关基因表达显著上调。基因集浓缩分析(GSEA)提示P53信号通路、DNA复制、半胱氨酸和蛋氨酸代谢通路与蒽环类药物敏感性有关。体细胞TP53突变是一种常见的遗传异常，在蒽环类药物敏感组中观察到，而CDH1突变出现在蒽环类药物耐药组。蒽环类药物敏感组和耐药组之间的免疫渗入模式存在极大差异。免疫相关的趋化因子和细胞因子、免疫调节因子和人类白细胞抗原基因在蒽环类药物敏感组显著上调。这些结果揭示了与蒽环类药物耐药性相关的潜在分子机制。
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.
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影响因子：
1.7
作者：
Knappskog S;Leirvaag B;Gansmo LB;Romundstad P;Hveem K;Vatten L;Lønning PE
通讯作者：
Lønning PE
影响因子：
7.7
作者：
McGuirk S;Audet-Delage Y;Annis MG;Xue Y;Vernier M;Zhao K;St-Louis C;Minarrieta L;Patten DA;Morin G;Greenwood CM;Giguère V;Huang S;Siegel PM;St-Pierre J
通讯作者：
St-Pierre J
影响因子：
5.8
作者：
Lehmann-Che, Jacqueline;Andre, Fabrice;de The, Hugues
通讯作者：
de The, Hugues
影响因子：
--
作者：
Hansen, Stine Ninel;Westergaard, David;Schrohl, Anne-Sofie
通讯作者：
Schrohl, Anne-Sofie
基于微阵列数据分析的乳腺癌阿霉素耐药基因鉴定
影响因子：
0.9
作者：
Chen Y;Lin Y;Cui Z
通讯作者：
Cui Z