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 alpha-1-antitrypsin, alpha1-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.

Cervical-vaginal fluid (CVF) is a potential rich source of biomarkers for enhancing our understanding of human parturition and pathologic conditions affecting pregnancy. In this study, we performed a comprehensive survey of the CVF proteome in pregnancy utilizing multidimensional liquid chromatography (2D-LC) coupled with mass spectrometry and gel-electrophoresis-based protein separation and identification. In total, 150 unique proteins were identified using multiple protein identification algorithms. Metabolism (32%) and immune response-related (22%) proteins are the major functional categories represented in the CVF proteome. A comparison of the CVF, serum, and amniotic fluid proteomes showed that 77 proteins are unique to CVF, while 56 and 17 CVF proteins also occur in serum and amniotic fluid, respectively. This data set provides a foundation for evaluation of these proteins as potential CVF biomarkers for noninvasive diagnosis of pregnancy-related disorders.

The characterization of cancer genomes has provided insight into somatically altered genes across tumors, transformed our understanding of cancer biology, and enabled tailoring of therapeutic strategies. However, the function of most cancer alleles remains mysterious, and many cancer features transcend their genomes. Consequently, tumor genomic characterization does not influence therapy for most patients. Approaches to understand the function and circuitry of cancer genes provide complementary approaches to elucidate both oncogene and non-oncogene dependencies. Emerging work indicates that the diversity of therapeutic targets engendered by non-oncogene dependencies is much larger than the list of recurrently mutated genes. Here we describe a framework for this expanded list of cancer targets, providing novel opportunities for clinical translation.