title: Molecular determinants for lymph node metastasis in clinically early-stage endometrial cancer.
abstract: Patients with occult lymph node metastasis in endometrioid-type endometrial cancer (EC) are prone to the development of recurrences and have worse outcomes compared with patients without lymph node metastasis. In the current study, the aim was to identify molecular parameters associated with lymph node metastasis in EC clinically early-stage disease. A univariate analysis of differentially expressed genes, proteins and clinicopathological parameters (including myometrial invasion and tumor grade) was performed, comparing EC patients with and without lymph node metastasis (n=262 patients from The Cancer Genome Atlas). Significant parameters were introduced in a multivariate model and a gene expression pathway analysis. Lymph node metastasis was associated with expression of 268 unique genes (P<0.001), 19 unique proteins (P<0.05), tumor grade and myometrial invasion in univariate analysis. Multivariate analysis demonstrated 10 genes independently associated with lymph node metastasis and 4 independently associated proteins. Myometrial invasion was the only independent clinicopathological parameter associated with lymph node status. The enrichment pathway analysis demonstrated that expression of epidermal growth factor receptor, Bcl2 antagonist of cell death and phosphatase and tensin homolog pathways were significantly involved in lymph node metastasis (P≤0.001). A gene expression signature to predict lymph node status in EC was created for future validation. Few studies have focused on the association between EC's molecular characteristics and nodal metastasis. Defining molecular risk factors for EC lymphatic nodal metastasis may help to individualize treatment and improve patient outcomes.
authors: Department of Women's Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA.
authors: Nadim
authors: N
authors: Bou Zgheib
authors: Department of Women's Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA; Chemical Biology and Molecular Medicine Program, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA.
authors: Douglas C
authors: DC
authors: Marchion
authors: Department of Women's Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA.
authors: Stephen H
authors: SH
authors: Bush
authors: Department of Women's Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA; Chemical Biology and Molecular Medicine Program, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA; Department of Oncologic Sciences, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA.
authors: Patricia L
authors: PL
authors: Judson
authors: Department of Women's Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA; Chemical Biology and Molecular Medicine Program, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA; Department of Oncologic Sciences, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA.
authors: Robert M
authors: RM
authors: Wenham
authors: Department of Women's Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA; Department of Oncologic Sciences, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA.
authors: Sachin M
authors: SM
authors: Apte
authors: Department of Women's Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA; Chemical Biology and Molecular Medicine Program, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA; Department of Oncologic Sciences, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA.
authors: Johnathan M
authors: JM
authors: Lancaster
authors: Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Iowa Hospital and Clinics, Iowa, IA 52242, USA.
authors: Jesus
authors: J
authors: Gonzalez-Bosquet
keywords: clinicopathological and molecular parameters; endometrial cancer; lymph node metastasis