title: Multiplexed immunofluorescence delineates proteomic cancer cell states associated with metabolism.
abstract: The phenotypic diversity of cancer results from genetic and nongenetic factors. Most studies of cancer heterogeneity have focused on DNA alterations, as technologies for proteomic measurements in clinical specimen are currently less advanced. Here, we used a multiplexed immunofluorescence staining platform to measure the expression of 27 proteins at the single-cell level in formalin-fixed and paraffin-embedded samples from treatment-naive stage II/III human breast cancer. Unsupervised clustering of protein expression data from 638,577 tumor cells in 26 breast cancers identified 8 clusters of protein coexpression. In about one-third of breast cancers, over 95% of all neoplastic cells expressed a single protein coexpression cluster. The remaining tumors harbored tumor cells representing multiple protein coexpression clusters, either in a regional distribution or intermingled throughout the tumor. Tumor uptake of the radiotracer 18F-fluorodeoxyglucose was associated with protein expression clusters characterized by hormone receptor loss,PTENalteration, andHER2gene amplification. Our study demonstrates an approach to generate cellular heterogeneity metrics in routinely collected solid tumor specimens and integrate them with in vivo cancer phenotypes.
authors.affiliation: Diagnostic Imaging and Biomedical Technologies, GE Global Research Center, Niskayuna, New York, USA.
authors.forename: Anup
authors.initials: A
authors.lastname: Sood
authors.affiliation: Department of Neurology.
authors.forename: Alexandra M
authors.initials: AM
authors.lastname: Miller
authors.affiliation: Department of Pathology.
authors.forename: Edi
authors.initials: E
authors.lastname: Brogi
authors.affiliation: Diagnostic Imaging and Biomedical Technologies, GE Global Research Center, Niskayuna, New York, USA.
authors.forename: Yunxia
authors.initials: Y
authors.lastname: Sui
authors.affiliation: Human Oncology and Pathogenesis Program.
authors.forename: Joshua
authors.initials: J
authors.lastname: Armenia
authors.affiliation: Diagnostic Imaging and Biomedical Technologies, GE Global Research Center, Niskayuna, New York, USA.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: McDonough
authors.affiliation: Diagnostic Imaging and Biomedical Technologies, GE Global Research Center, Niskayuna, New York, USA.
authors.forename: Alberto
authors.initials: A
authors.lastname: Santamaria-Pang
authors.affiliation: Department of Radiology, and.
authors.forename: Sean
authors.initials: S
authors.lastname: Carlin
authors.affiliation: Human Oncology and Pathogenesis Program.
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Stamper
authors.affiliation: Human Oncology and Pathogenesis Program.
authors.forename: Carl
authors.initials: C
authors.lastname: Campos
authors.affiliation: Diagnostic Imaging and Biomedical Technologies, GE Global Research Center, Niskayuna, New York, USA.
authors.forename: Zhengyu
authors.initials: Z
authors.lastname: Pang
authors.affiliation: Diagnostic Imaging and Biomedical Technologies, GE Global Research Center, Niskayuna, New York, USA.
authors.forename: Qing
authors.initials: Q
authors.lastname: Li
authors.affiliation: Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York, USA.
authors.forename: Elisa
authors.initials: E
authors.lastname: Port
authors.affiliation: Department of Molecular and Medical Pharmacology, UCLA, Los Angeles, California, USA.
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Graeber
authors.affiliation: Human Oncology and Pathogenesis Program.|Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, New York, USA.
authors.forename: Nikolaus
authors.initials: N
authors.lastname: Schultz
authors.affiliation: Diagnostic Imaging and Biomedical Technologies, GE Global Research Center, Niskayuna, New York, USA.
authors.forename: Fiona
authors.initials: F
authors.lastname: Ginty
authors.affiliation: Department of Radiology, and.
authors.forename: Steven M
authors.initials: SM
authors.lastname: Larson
authors.affiliation: Department of Neurology.|Human Oncology and Pathogenesis Program.|Department of Pharmacology, Weill Cornell Medical School, New York, New York, USA.
authors.forename: Ingo K
authors.initials: IK
authors.lastname: Mellinghoff