通过反相蛋白质阵列鉴定三阴性乳腺癌亚型并与mRNA分子亚型进行比较。
Reverse phase protein array identification of triple-negative breast cancer subtypes and comparison with mRNA molecular subtypes.
作者信息
Masuda Hiroko, Qi Yuan, Liu Shuying, Hayashi Naoki, Kogawa Takahiro, Hortobagyi Gabriel N, Tripathy Debu, Ueno Naoto T
机构信息
Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
出版信息
Oncotarget. 2017 Jul 31;8(41):70481-70495. doi: 10.18632/oncotarget.19719. eCollection 2017 Sep 19.
BACKGROUND
Reverse phase protein array (RPPA) analysis, allows investigation of potential targets at the functional protein level,. We identified TNBC subtypes at the protein level using RPPA and compared them with mRNA molecular subtypes (TNBCtype, TNBCtype-4, and PAM50) that is unique in its availability of both RPPA and mRNA analyses.
METHODS
We classified the samples from 80 TNBC patients using both k-means and hierarchical consensus clustering analysis and performed Ingenuity Pathway Analysis. We also investigated whether we could reproduce the mRNA molecular subtypes using the RPPA dataset.
RESULTS
Both clustering methods divided all samples into 2 clusters that were biologically the same. The top canonical pathways included inflammation, hormonal receptors, and MAPK signaling pathways for the first cluster ["inflammation and hormonal-related (I/H) subtype"] and the GADD45, DNA damage, and p53 signaling pathways for the second cluster ["DNA damage (DD)-related subtype"]. Further k-means cluster analysis identified 5 TNBC clusters. Comparison between sample classification using the 5 RPPA-based k-means cluster subtypes and 6 gene-expression-based TNBCtype molecular subtypes showed significant association between the 2 classifications (p = 0.017).
CONCLUSIONS
The I/H and DD subtypes identified by RPPA advance our understanding of TNBC's heterogeneity from the functional proteomic perspective.
背景
反相蛋白质阵列（RPPA）分析能够在功能蛋白水平上研究潜在靶点。我们使用RPPA在蛋白水平鉴定三阴性乳腺癌（TNBC）亚型，并将其与mRNA分子亚型（TNBCtype、TNBCtype - 4和PAM50）进行比较，该研究在同时具备RPPA和mRNA分析方面具有独特性。
方法
我们使用k均值聚类分析和层次一致性聚类分析对80例TNBC患者的样本进行分类，并进行了 Ingenuity 通路分析。我们还研究了能否使用RPPA数据集重现mRNA分子亚型。
结果
两种聚类方法都将所有样本分为两个生物学上相同的簇。第一个簇["炎症和激素相关（I/H）亚型"]的主要经典通路包括炎症、激素受体和MAPK信号通路，第二个簇["DNA损伤（DD）相关亚型"]的主要经典通路包括GADD45、DNA损伤和p53信号通路。进一步的k均值聚类分析确定了5个TNBC簇。基于5种基于RPPA的k均值聚类亚型的样本分类与基于6种基因表达的TNBCtype分子亚型之间的比较显示，这两种分类之间存在显著关联（p = 0.017）。
结论
RPPA鉴定出的I/H和DD亚型从功能蛋白质组学角度推进了我们对TNBC异质性的理解。
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