The presence of
lymph node metastases in
endometrial cancer patients is a critical factor guiding treatment decisions; however, surgical and imaging methods for their detection are limited by morbidity and inaccuracy. To determine if sera can predict the presence of positive lymph nodes, sera collected from
endometrial cancer patients with or without
lymph node metastases, and benign gynecology surgical patients (N = 20 per group) were subjected to electron spray ionization mass spectrometry (ES-MS). Peaks that were significantly different among the groups were evaluated by leave one out cross validation (LOOCV) for their ability to differentiation between the groups.
Proteins in the peaks were identified by MS/MS of five specimens in each group. Ingenuity Pathway Analysis was used to predict pathways regulated by the
protein profiles. LOOCV of sera
protein discriminated between each of the group comparisons and predicted positive lymph nodes. Pathways implicated in
metastases included loss of PTEN activation and PI3K, AKT and PKA activation, leading to calcium signaling, oxidative phosphorylation and
estrogen receptor-induced transcription, leading to platelet activation, epithelial-to-mesenchymal transition and senescence. Upstream activators implicated in these events included neurostimulation and
inflammation, activation of
G-Protein-Coupled Receptor Gβγ, loss of HER-2 activation and upregulation of the
insulin receptor.