title: Ascites analysis by a microfluidic chip allows tumor-cell profiling.
abstract: Ascites tumor cells (ATCs) represent a potentially valuable source of cells for monitoring treatment of ovarian cancer as it would obviate the need for more invasive surgical biopsies. The ability to perform longitudinal testing of ascites in a point-of-care setting could significantly impact clinical trials, drug development, and clinical care. Here, we developed a microfluidic chip platform to enrich ATCs from highly heterogeneous peritoneal fluid and then perform molecular analyses on these cells. We evaluated 85 putative ovarian cancer protein markers and found that nearly two-thirds were either nonspecific for malignant disease or had low abundance. Using four of the most promising markers, we prospectively studied 47 patients (33 ovarian cancer and 14 control). We show that a marker set (ATCdx) can sensitively and specifically map ATC numbers and, through its reliable enrichment, facilitate additional treatment-response measurements related to proliferation, protein translation, or pathway inhibition.
authors.affiliation: Center for Systems Biology, Massachusetts General Hospital, Boston, MA 02114.
authors.forename: Vanessa M
authors.initials: VM
authors.lastname: Peterson
authors.forename: Cesar M
authors.initials: CM
authors.lastname: Castro
authors.forename: Jaehoon
authors.initials: J
authors.lastname: Chung
authors.forename: Nathan C
authors.initials: NC
authors.lastname: Miller
authors.forename: Adeeti V
authors.initials: AV
authors.lastname: Ullal
authors.forename: Maria D
authors.initials: MD
authors.lastname: Castano
authors.forename: Richard T
authors.initials: RT
authors.lastname: Penson
authors.forename: Hakho
authors.initials: H
authors.lastname: Lee
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Birrer
authors.forename: Ralph
authors.initials: R
authors.lastname: Weissleder
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001201:Ascites / Q000378:metabolism* / Q000473:pathology; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001706:Biopsy; D005260:Female; D006801:Humans; D046210:Microfluidic Analytical Techniques; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism*; D010051:Ovarian Neoplasms / Q000378:metabolism* / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins
keywords: biomarkers; molecular profiling; personalized medicine