Aberrant Gene Expression Predicts Metastatic Endometrial and Lung Cancers

The spread of cancer cells from the initial site of occurrence, the primary site, to other secondary tissues is called metastasis, and contributes to poor or limited response of cancer cells to treatments, which results in death. For example, cancer cells initially in the lungs can begin to spread to other organs, including the brain and liver.

Gynecologic cancer typically originates from the female reproductive organs, and includes endometrial and ovarian cancer, among others. Survival rates are typically very poor for these cancer-types, with limited response to existing therapies and a major reason for poor survival rates is late diagnoses, by which time the cancer cells have spread to secondary sites.

Scientists from Georgia State University (Atlanta, GA, USA) and the University of Oklahoma College of Medicine (Oklahoma City, OK, USA) obtained more than a hundred clinical endometrial cancer specimens and matching serum. Using multiplex arrays and a variety of experimental approaches, they analyzed the specimens for gene targets that positively or negatively correlated with metastatic potential of the tumors. Data were translated to reflect the patient's age at diagnosis, disease stage, grade and histology.

Serum specimens were evaluated for levels of c-peptide, interleukin-6 (IL-6,) insulin, leptin, monocyte chemoattractant protein-1 (MCP-1 or CCL2) and tumor necrosis factor alpha (TNFα) using a custom-made multiplex kit subset of the MILLIPLEX MAP Human Metabolic Hormone Magnetic Bead Panel (EMD Millipore; Billerica, MA, USA), for levels of adipsin and adiponectin, using the Bio-Plex Pro Human Diabetes Adipsin and Adiponectin Assay (BIO-RAD Laboratories Inc., Hercules, CA, USA; www.bio-rad.com) and for levels of angiopoietin-2, follistatin, G-CSF, HGF, IL-8, leptin, PDGF-BB, PECAM-1 and VEGF, they used the Bio-Rad Bio-Plex Pro diabetes kit.

The scientists found that enhanced neuropilin-1 (NRP-1) expression significantly correlated with increased tumoral expression of vascular endothelial growth factor 2 (VEGFR2) and serum levels of hepatocyte growth factor (HGF) and cell growth-stimulating factor (C-GSF). Tumoral NRP-1 also was positively associated with expression of neural precursor cell expressed developmentally down-regulated protein 9 (NEDD9), a pro-metastatic protein. In the highly metastatic lung cancer cell line (H1792), stable LKB1 depletion caused increased migration in vitro and accentuated NRP-1 and NEDD9 expression in vivo.

Imoh S. Okon, PhD, a professor and lead author of the study said, “In this study, we found that enhanced neuropilin-1 (NRP-1) and NEDD9 levels in endometrial and lung cancer positively correlated with metastasis, while liver kinase B1 (LKB1) inhibited the migration of cancer cells. Our study provides strong translational potential with respect to biomarkers that play critical roles in the development of endometrial/lung tumors.” The study was published on December 20, 2015, in the journal Oncotarget.

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