Simultaneous measurement of 92 serum protein biomarkers for the development of a multiprotein classifier for ovarian cancer detection

Amy P.N. Skubitz, Kristin L.M. Boylan, Kate Geschwind, Qing Cao, Timothy K. Starr, Melissa A. Geller, Joseph Celestino, Robert C. Bast, Karen H. Lu, Joseph S. Koopmeiners

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2 Scopus citations


The best known ovarian cancer biomarker, CA125, is neither adequately sensitive nor specific for screening the general population. By using a combination of proteins for screening, it may be possible to increase the sensitivity and specificity over CA125 alone. In this study, we used Proseek Multiplex Oncology II plates to simultaneously measure the expression of 92 cancer-related proteins in serum using proximity extension assays. This technology combines the sensitivity of the PCR with the specificity of antibodybased detection methods, allowing multiplex biomarker detection and high-throughput quantification. We analyzed 1 μL of sera fromeach of 61 womenwith ovarian cancer and compared the values obtained with those from 88 age-matched healthy women. Principle component analysis and unsupervised hierarchical clustering separated the ovarian cancer patients from the healthy, with minimal misclassification. Data from the Proseek plates for CA125 levels exhibited a strong correlation with clinical values for CA125. We identified 52 proteins that differed significantly (P < 0.006) between ovarian cancer and healthy samples, several of which are novel serum biomarkers for ovarian cancer. In total, 40 proteins had an estimated area under the ROC curve of 0.70 or greater, suggesting their potential to serve as biomarkers for ovarian cancer. CA125 alone achieved a sensitivity of 93.4% at a specificity of 98%. By adding the Oncology II values for five proteins to CA125 in a multiprotein classifier, we increased the assay sensitivity to 98.4% at a specificity of 98%, thereby improving the sensitivity and specificity of CA125 alone.

Original languageEnglish (US)
Pages (from-to)171-183
Number of pages13
JournalCancer Prevention Research
Issue number3
StatePublished - Mar 2019

Bibliographical note

Funding Information:
This work was supported by a grant from the Minnesota Ovarian Cancer Alliance (A.P.N. Skubitz), the Randy Shaver Cancer Research and Community Fund (T.K. Starr), Masonic Cancer Center (T.K. Starr), and the Masonic Cancer Center Support Grant for the Biostatistics Core (Q. Cao and J.S. Koopmeiners). Funding for R.C. Bast, Jr., K.H. Lu, and J. Celestino was provided by the Early Detection Research Network (5 U01 CA200462-02), the MD Anderson Ovarian SPORE (P50 CA83639 and P50 CA217685), National Cancer Institute, Department of Health and Human Services, the Cancer Prevention Research Institute of Texas (RP160145), Golfer's Against Cancer, the Mossy Foundation, the Roberson Endowment, National Foundation for Cancer Research, and generous donations from Stuart and Gaye Lynn Zarrow.

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