A senescence-associated signature refines the classification of different modification patterns and characterization of tumor immune microenvironment infiltration in triple-negative breast cancer.
A senescence-associated signature refines the classification of different modification patterns and characterization of tumor immune microenvironment infiltration in triple-negative breast cancer.
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DOI：
10.3389/fphar.2023.1191910
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发表时间：
2023
影响因子：
5.6
通讯作者：
中科院分区：
文献类型：
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作者：
背景：近年来研究发现衰老相关基因在肿瘤生物学过程中起着重要作用。我们的目的是分析衰老相关基因在三阴性乳腺癌（TNBC）中的特点和作用。 研究方法：我们系统地筛选衰老相关分泌表型（SASP）基因的基础上，基因表达信息的TCGA数据库。根据衰老相关基因的表达水平，使用无监督聚类算法将TNBC分为两种亚型，即TNBC SASP 1和TNBC SASP 2。然后，我们对这两种亚型进行了基因表达、富集途径、免疫浸润、突变谱表征、药物敏感性和预后价值分析。验证了该分类模型的可靠性和预后预测效用。通过组织芯片在TNBC中全面鉴定和验证最具诊断相关性的基因FAM 3B。 结果如下：根据与衰老相关的分泌表型基因的集合，TNBC被分为两个衰老相关的亚型，TNBC SASP 1和TNBC SASP 2，其中TNBC SASP 1亚型具有较差的预后。TNBCSASP 1亚型是免疫抑制的，具有抑制的免疫相关信号传导途径和低免疫细胞浸润。该突变对TP 53和TGF-β通路的影响可能与TNBCSASP 1亚型的不良预后有关。药物敏感性分析显示，AMG. 706、CCT 007093和CHIR. 99021是TNBC SASP 1亚型的潜在靶向药物。最后，FAM 3B是影响三阴性乳腺癌患者预后的关键生物标志物。与正常乳腺组织相比，FAM 3B在三阴性乳腺癌中的表达降低。生存分析显示，FAM 3B高表达的三阴性乳腺癌患者的总生存期显著较短。 结论：具有不同修饰模式的衰老相关特征对于提供对TNBC生物过程的更好理解具有关键潜力，并且FAM 3B可以用作TNBC治疗的适用靶标。
Background: Recent studies have found that senescence-associated genes play a significant role in cancer biological processes. We aimed to analyze the characteristics and role of senescence-associated genes in triple-negative breast cancer (TNBC). Methods: We systematically screened senescence-associated secretory phenotype (SASP) genes based on the gene expression information in the TCGA database. According to the expression levels of senescence-associated genes, TNBC was classified into two subtypes, namely, TNBCSASP1 and TNBCSASP2, using an unsupervised cluster algorithm. We then performed gene expression, enrichment pathway, immune infiltration, mutational profile characterization, drug sensitivity and prognostic value analyses for the two subtypes. The reliability and prognostic predictive utility of this classification model were validated. The most prognostically relevant gene, FAM3B, was comprehensively identified and validated by tissue microarray in TNBC. Results: TNBC was classified into two senescence-associated subtypes, TNBCSASP1 and TNBCSASP2, based on the set of senescence-associated secretory phenotype genes, among which the TNBCSASP1 subtype had a poor prognosis. The TNBCSASP1 subtype was immunosuppressed, with suppressed immune-related signaling pathways and low immune cell infiltration. The effect of the mutation on the TP53 and TGF-β pathways could be related to the poor prognosis of the TNBCSASP1 subtype. Drug sensitivity analysis showed that AMG.706, CCT007093, and CHIR.99021 were potential targeted drugs for the TNBCSASP1 subtype. Finally, FAM3B was a key biomarker affecting the prognosis of patients with triple-negative breast cancer. Compared to normal breast tissue, the expression of FAM3B was reduced in triple-negative breast cancer. Survival analysis showed that overall survival was significantly shorter in triple-negative breast cancer patients with high FAM3B expression. Conclusion: A senescence-associated signature with different modification patterns has critical potential for providing a better understanding of TNBC biological processes, and FAM3B might serve as an applicable target for TNBC therapy.
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影响因子：
64.5
作者：
López-Otín C;Blasco MA;Partridge L;Serrano M;Kroemer G
通讯作者：
Kroemer G
DOI：
10.1001/jama.2011.593
发表时间：
2011-05-11
期刊：
JAMA
影响因子：
--
作者：
Hatzis C;Pusztai L;Valero V;Booser DJ;Esserman L;Lluch A;Vidaurre T;Holmes F;Souchon E;Wang H;Martin M;Cotrina J;Gomez H;Hubbard R;Chacón JI;Ferrer-Lozano J;Dyer R;Buxton M;Gong Y;Wu Y;Ibrahim N;Andreopoulou E;Ueno NT;Hunt K;Yang W;Nazario A;DeMichele A;O'Shaughnessy J;Hortobagyi GN;Symmans WF
通讯作者：
Symmans WF
影响因子：
5.8
作者：
Liberzon, Arthur;Subramanian, Aravind;Mesirov, Jill P.
通讯作者：
Mesirov, Jill P.
影响因子：
8.8
作者：
通讯作者：
--
影响因子：
11.2
作者：
Murali B;Ren Q;Luo X;Faget DV;Wang C;Johnson RM;Gruosso T;Flanagan KC;Fu Y;Leahy K;Alspach E;Su X;Ross MH;Burnette B;Weilbaecher KN;Park M;Mbalaviele G;Monahan JB;Stewart SA
通讯作者：
Stewart SA