PDF(Pubmed)
Abstract：
Triple-negative breast cancer (TNBC) is a rare and aggressive breast cancer subtype. Unlike the estrogen receptor-positive subtype, whose recurrence risk can be predicted by gene expression-based signature, TNBC is more heterogeneous, with diverse drug sensitivity levels to standard regimens. This study explored the benefit of gene expression-based profiling for classifying the molecular subtypes of Thai TNBC patients.
The nCounter-based Breast 360 gene expression was used to classify Thai TNBC retrospective cohort subgroups. Their expression profiles were then compared against the previously established TNBC classification system. The differential characteristics of the tumor microenvironment and DNA damage repair signatures across subgroups were also explored.
Thai TNBC cohort could be classified into four main subgroups, corresponding to the LAR, BL-2, and M subtypes based on Lehmann\'s TNBC classification. The PAM50 gene set classified most samples as basal-like subtypes except for Group 1. Group 1 exhibited similar enrichment of the metabolic and hormone response pathways to the LAR subtype. Group 2 shared pathway activation with the BL-2 subtype. Group 3 showed an increase in the EMT pathway, similar to the M subtype. Group 4 showed no correlation with Lehmann\'s TNBC. The tumor microenvironment (TME) analysis showed high TME cell abundance with increased expression of immune blockade genes in Group 2. Group 4 exhibited low TME cell abundance and reduced immune blockade gene expressions. We also observed distinct signatures of the DNA double-strand break repair genes in Group 1.
Our study reported unique characteristics between the four TNBC subgroups and showed the potential use of immune checkpoint and PARP inhibitors in subsets of Thai TNBC patients. Our findings warrant further clinical investigation to validate TNBC\'s sensitivity to these regimens.
The nCounter-based Breast 360 gene expression was used to classify Thai TNBC retrospective cohort subgroups. Their expression profiles were then compared against the previously established TNBC classification system. The differential characteristics of the tumor microenvironment and DNA damage repair signatures across subgroups were also explored.
Thai TNBC cohort could be classified into four main subgroups, corresponding to the LAR, BL-2, and M subtypes based on Lehmann\'s TNBC classification. The PAM50 gene set classified most samples as basal-like subtypes except for Group 1. Group 1 exhibited similar enrichment of the metabolic and hormone response pathways to the LAR subtype. Group 2 shared pathway activation with the BL-2 subtype. Group 3 showed an increase in the EMT pathway, similar to the M subtype. Group 4 showed no correlation with Lehmann\'s TNBC. The tumor microenvironment (TME) analysis showed high TME cell abundance with increased expression of immune blockade genes in Group 2. Group 4 exhibited low TME cell abundance and reduced immune blockade gene expressions. We also observed distinct signatures of the DNA double-strand break repair genes in Group 1.
Our study reported unique characteristics between the four TNBC subgroups and showed the potential use of immune checkpoint and PARP inhibitors in subsets of Thai TNBC patients. Our findings warrant further clinical investigation to validate TNBC\'s sensitivity to these regimens.
摘要：
■三阴性乳腺癌（TNBC）是一种罕见的侵袭性乳腺癌亚型。与雌激素受体阳性亚型不同,其复发风险可以通过基于基因表达的签名来预测，TNBC更异质，对标准方案有不同的药物敏感性。这项研究探索了基于基因表达的谱分析对泰国TNBC患者分子亚型分类的益处。
■基于nCounter的乳房360基因表达用于对泰国TNBC回顾性队列亚组进行分类。然后将它们的表达谱与先前建立的TNBC分类系统进行比较。还探索了肿瘤微环境的差异特征和亚组之间的DNA损伤修复特征。
■泰国TNBC队列可以分为四个主要亚组，对应于LAR，基于Lehmann的TNBC分类的BL-2和M亚型。PAM50基因集将大多数样品分类为基底样亚型,除了组1。第1组表现出与LAR亚型相似的代谢和激素反应途径富集。第2组与BL-2亚型共享通路激活。第3组显示EMT途径增加，类似于M亚型。第4组与Lehmann的TNBC无相关性。肿瘤微环境（TME）分析显示，第2组中TME细胞丰度高，免疫阻断基因表达增加。第4组表现出低TME细胞丰度和降低的免疫阻断基因表达。我们还观察到第1组中DNA双链断裂修复基因的不同特征。
■我们的研究报告了四个TNBC亚群之间的独特特征，并显示了在泰国TNBC患者亚群中免疫检查点和PARP抑制剂的潜在用途。我们的发现需要进一步的临床研究来验证TNBC对这些方案的敏感性。
■基于nCounter的乳房360基因表达用于对泰国TNBC回顾性队列亚组进行分类。然后将它们的表达谱与先前建立的TNBC分类系统进行比较。还探索了肿瘤微环境的差异特征和亚组之间的DNA损伤修复特征。
■泰国TNBC队列可以分为四个主要亚组，对应于LAR，基于Lehmann的TNBC分类的BL-2和M亚型。PAM50基因集将大多数样品分类为基底样亚型,除了组1。第1组表现出与LAR亚型相似的代谢和激素反应途径富集。第2组与BL-2亚型共享通路激活。第3组显示EMT途径增加，类似于M亚型。第4组与Lehmann的TNBC无相关性。肿瘤微环境（TME）分析显示，第2组中TME细胞丰度高，免疫阻断基因表达增加。第4组表现出低TME细胞丰度和降低的免疫阻断基因表达。我们还观察到第1组中DNA双链断裂修复基因的不同特征。
■我们的研究报告了四个TNBC亚群之间的独特特征，并显示了在泰国TNBC患者亚群中免疫检查点和PARP抑制剂的潜在用途。我们的发现需要进一步的临床研究来验证TNBC对这些方案的敏感性。
