Multi-protein spatial signatures in ductal carcinoma in situ (DCIS) of breast.

Multi-protein spatial signatures in ductal carcinoma in situ (DCIS) of breast.
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乳腺导管原位癌(DCIS)中多蛋白质空间特征的研究

DOI:
10.1038/s41416-020-01216-6
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发表时间:
2021-03
影响因子:
8.8
通讯作者:
Ginty F
Ginty F
中科院分区:
医学1区
文献类型:
--
作者:
Badve SS;Cho S;Gökmen-Polar Y;Sui Y;Chadwick C;McDonough E;Sood A;Taylor M;Zavodszky M;Tan PH;Gerdes M;Harris AL;Ginty F

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关于DCIS细胞组成及其与乳腺癌事件(BCE)的关系的知识有限。使用免疫荧光多路复用(MxIF)对FFPE DCIS组织微阵列中的32种细胞生物标志物进行成像和定量。对来自51名患者(非BCE病例的中位随访时间为9年)的75,000多个DCIS细胞进行了分析,以预测BCE的特征。使用K均值聚类来评估上皮标志物与ER和HER 2的细胞共表达。只有ER、PR和HER 2与BCE显著相关。聚类分析鉴定了具有不同水平的ER、Her 2、cMET和SLC 7A 5的6个不同细胞组。聚类1和聚类3不显著。聚类2和4(高ER/低HER 2和SLC 7A 5/混合cMET)与低BCE风险显著相关(P = 0.001和P = 0.034),而聚类6(高HER 2/低ER、cMET和SLC 7A 5)与风险增加相关(P = 0.018)。聚类5(类似于聚类6,除了高SLC 7A 5)趋向于显著性(P = 0.072)。基于这4个聚类的连续表达评分(Escore)预测BCE的可能性(AUC = 0.79,对数秩检验P = 5E-05; LOOCV AUC = 0.74,对数秩检验P = 0.006)。有限组织的多重空间分析是生物标志物分析和预测BCE的新方法。需要在更大的队列中进一步验证Escore。
There is limited knowledge about DCIS cellular composition and relationship with breast cancer events (BCE). Immunofluorescence multiplexing (MxIF) was used to image and quantify 32 cellular biomarkers in FFPE DCIS tissue microarrays. Over 75,000 DCIS cells from 51 patients (median 9 years follow-up for non-BCE cases) were analysed for profiles predictive of BCE. K-means clustering was used to evaluate cellular co-expression of epithelial markers with ER and HER2. Only ER, PR and HER2 significantly correlated with BCE. Cluster analysis identified 6 distinct cell groups with different levels of ER, Her2, cMET and SLC7A5. Clusters 1 and 3 were not significant. Clusters 2 and 4 (high ER/low HER2 and SLC7A5/mixed cMET) significantly correlated with low BCE risk (P = 0.001 and P = 0.034), while cluster 6 (high HER2/low ER, cMET and SLC7A5) correlated with increased risk (P = 0.018). Cluster 5 (similar to cluster 6, except high SLC7A5) trended towards significance (P = 0.072). A continuous expression score (Escore) based on these 4 clusters predicted likelihood of BCE (AUC = 0.79, log-rank test P = 5E–05; LOOCV AUC = 0.74, log-rank test P = 0.006). Multiplexed spatial analysis of limited tissue is a novel method for biomarker analysis and predicting BCEs. Further validation of Escore is needed in a larger cohort.
DOI: 10.1186/s12935-017-0427-5
发表时间: 2017
影响因子: 5.8
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Nasir A;Holzer TR;Chen M;Man MZ;Schade AE
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DOI: 10.1038/npjbcancer.2016.14
发表时间: 2016-05-18
期刊: NPJ BREAST CANCER
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DOI: 10.1056/nejmoa1602253
发表时间: 2016-08-25
影响因子: 158.5
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DOI: 10.2147/bctt.s131284
发表时间: 2017
期刊: Breast cancer (Dove Medical Press)
影响因子: --
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Delou JMA;Vignal GM;Índio-do-Brasil V;Accioly MTS;da Silva TSL;Piranda DN;Sobral-Leite M;de Carvalho MA;Capella MAM;Vianna-Jorge R
通讯作者: Vianna-Jorge R