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

Background There is limited knowledge about DCIS cellular composition and relationship with breast cancer events (BCE). Methods 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 (media...

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Vydáno v:British journal of cancer Ročník 124; číslo 6; s. 1150 - 1159
Hlavní autoři: Badve, Sunil S., Cho, Sanghee, Gökmen-Polar, Yesim, Sui, Yunxia, Chadwick, Chrystal, McDonough, Elizabeth, Sood, Anup, Taylor, Marian, Zavodszky, Maria, Tan, Puay Hoon, Gerdes, Michael, Harris, Adrian L., Ginty, Fiona
Médium: Journal Article
Jazyk:angličtina
Vydáno: London Nature Publishing Group UK 16.03.2021
Nature Publishing Group
Témata:
631/67/1347
692/53/2422
Aged
Antineoplastic Combined Chemotherapy Protocols - therapeutic use
Biomarkers
Biomarkers, Tumor - metabolism
Biomedical and Life Sciences
Biomedicine
Breast cancer
Breast Neoplasms - metabolism
Breast Neoplasms - pathology
Breast Neoplasms - therapy
Cancer Research
Carcinoma, Ductal, Breast - metabolism
Carcinoma, Ductal, Breast - pathology
Carcinoma, Ductal, Breast - therapy
Carcinoma, Intraductal, Noninfiltrating - metabolism
Carcinoma, Intraductal, Noninfiltrating - pathology
Carcinoma, Intraductal, Noninfiltrating - therapy
Cluster analysis
Combined Modality Therapy
Drug Resistance
Epidemiology
ErbB-2 protein
Female
Follow-Up Studies
Humans
Immunofluorescence
Mastectomy - methods
Middle Aged
Molecular Medicine
Oncology
Prognosis
Retrospective Studies
Survival Rate
ISSN:0007-0920, 1532-1827, 1532-1827
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Shrnutí:Background There is limited knowledge about DCIS cellular composition and relationship with breast cancer events (BCE). Methods 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. Results 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). Conclusion 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.
Bibliografie:ObjectType-Article-1
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ISSN:0007-0920
1532-1827
1532-1827
DOI:10.1038/s41416-020-01216-6