title: Detection of cervical cancer biomarker patterns in blood plasma and urine by differential scanning calorimetry and mass spectrometry.
abstract: Improved methods for the accurate identification of both the presence and severity of cervical intraepithelial neoplasia (CIN) and extent of spread of invasive carcinomas of the cervix (IC) are needed. Differential scanning calorimetry (DSC) has recently been shown to detect specific changes in the thermal behavior of blood plasma proteins in several diseases. This methodology is being explored to provide a complementary approach for screening of cervical disease. The present study evaluated the utility of DSC in differentiating between healthy controls, increasing severity of CIN and early and advanced IC. Significant discrimination was apparent relative to the extent of disease with no clear effect of demographic factors such as age, ethnicity, smoking status and parity. Of most clinical relevance, there was strong differentiation of CIN from healthy controls and IC, and amongst patients with IC between FIGO Stage I and advanced cancer. The observed disease-specific changes in DSC profiles (thermograms) were hypothesized to reflect differential expression of disease biomarkers that subsequently bound to and affected the thermal behavior of the most abundant plasma proteins. The effect of interacting biomarkers can be inferred from the modulation of thermograms but cannot be directly identified by DSC. To investigate the nature of the proposed interactions, mass spectrometry (MS) analyses were employed. Quantitative assessment of the low molecular weight protein fragments of plasma and urine samples revealed a small list of peptides whose abundance was correlated with the extent of cervical disease, with the most striking plasma peptidome data supporting the interactome theory of peptide portioning to abundant plasma proteins. The combined DSC and MS approach in this study was successful in identifying unique biomarker signatures for cervical cancer and demonstrated the utility of DSC plasma profiles as a complementary diagnostic tool to evaluate cervical cancer health.
authors.affiliation: James Graham Brown Cancer Center, University of Louisville, Louisville, Kentucky, United States of America ; Department of Medicine, University of Louisville, Louisville, Kentucky, United States of America.
authors.forename: Nichola C
authors.initials: NC
authors.lastname: Garbett
authors.affiliation: Department of Medicine, University of Louisville, Louisville, Kentucky, United States of America ; Center for Environmental Genomics and Integrative Biology, University of Louisville, Louisville, Kentucky, United States of America.
authors.forename: Michael L
authors.initials: ML
authors.lastname: Merchant
authors.affiliation: James Graham Brown Cancer Center, University of Louisville, Louisville, Kentucky, United States of America ; Department of Medicine, University of Louisville, Louisville, Kentucky, United States of America ; Division of Gynecologic Oncology, University of Louisville, Louisville, Kentucky, United States of America.
authors.forename: C William
authors.initials: CW
authors.lastname: Helm
authors.affiliation: James Graham Brown Cancer Center, University of Louisville, Louisville, Kentucky, United States of America ; Department of Medicine, University of Louisville, Louisville, Kentucky, United States of America.
authors.forename: Alfred B
authors.initials: AB
authors.lastname: Jenson
authors.affiliation: James Graham Brown Cancer Center, University of Louisville, Louisville, Kentucky, United States of America ; Department of Medicine, University of Louisville, Louisville, Kentucky, United States of America ; Center for Environmental Genomics and Integrative Biology, University of Louisville, Louisville, Kentucky, United States of America ; Robley Rex Veterans Affairs Medical Center, Louisville, Kentucky, United States of America.
authors.forename: Jon B
authors.initials: JB
authors.lastname: Klein
authors.affiliation: James Graham Brown Cancer Center, University of Louisville, Louisville, Kentucky, United States of America ; Department of Medicine, University of Louisville, Louisville, Kentucky, United States of America.
authors.forename: Jonathan B
authors.initials: JB
authors.lastname: Chaires
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D014408:Biomarkers, Tumor / Q000097:blood* / Q000737:chemistry / Q000652:urine*; D002152:Calorimetry, Differential Scanning; D018450:Disease Progression; D005260:Female; D006801:Humans; D013058:Mass Spectrometry; D008875:Middle Aged; D008969:Molecular Sequence Data; D013817:Thermography; D002583:Uterine Cervical Neoplasms / Q000097:blood* / Q000175:diagnosis / Q000652:urine*; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor