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Article

Identification of Novel Protein Biomarkers of Preterm Birth in Human Cervical−Vaginal Fluid

Supporting Info

Leonardo Pereira,^† Ashok P. Reddy, Thomas Jacob, Archana Thomas, Kimberly A. Schneider, Surendra Dasari,^‡ Jodi A. Lapidus, Xinfang Lu, Matthew Rodland,^‡ Charles T. Roberts, Jr.,^‡ Michael G. Gravett,^§ and Srinivasa R. Nagalla*^‡

Departments of Pediatrics and Obstetrics and Gynecology, Oregon Health and Science University, Portland, Oregon 97239, Department of Obstetrics and Gynecology, University of Washington, Seattle, Washington 98101, and ProteoGenix, Inc., Portland, Oregon 97213

J. Proteome Res., 2007, 6 (4), pp 1269–1276

DOI: 10.1021/pr0605421

Publication Date (Web): March 21, 2007

†

Department of Obstetrics and Gynecology, Oregon Health and Science University.

ProteoGenix, Inc

‡

Department of Pediatrics, Oregon Health and Science University.

University of Washington.

To whom correspondence should be addressed. E-mail, nagallas@ohsu.edu; tel, 503-494-1928; fax, 503-494-4821.

Abstract

Spontaneous preterm birth (SPTB) is a major contributor to perinatal morbidity and mortality. However, the diagnosis of preterm labor (PTL) that leads to preterm birth is difficult, and there is a pressing need for improved diagnosis. We utilized multidimensional liquid chromatography-tandem mass spectrometry (LC/LC−MS/MS; MudPIT) and Fluorescence two-dimensional differential in-gel electrophoresis (2D-DIGE) to identify potential biomarkers of PTL and SPTB. MudPIT analysis identified 205 proteins in cervical−vaginal fluid (CVF), 28 of which exhibited significant differences in pairwise and progressive comparisons. Calgranulins, annexins, S100 calcium-binding protein A7, and epidermal fatty acid binding protein were abundant in CVF and differentially present in PTL and SPTB samples, as were the serum proteins α-1-antitrypsin, α1-acid glycoprotein, haptoglobin, serotransferrin, and vitamin D binding protein. 2D-DIGE identified 17 proteins that were significantly differentially present in PTL and SPTB. Immunoblotting with specific antibodies confirmed the differences and trends of selected markers. Further characterization and quantification of these markers in a larger cohort of subjects may provide the basis for new tests for the early, noninvasive positive prediction of SPTB.

Keywords: Vaginal fluid • Preterm labor • Biomarkers • Prematurity • Pregnancy

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