Bioinformatics reveal elevated levels of Myosin Vb in uterine corpus endometrial carcinoma patients which correlates to increased cell metabolism and poor prognosis

Abstract

Carcinoma of the endometrium of the uterus is the most common female pelvic malignancy. Although uterine corpus endometrial cancer (UCEC) has a favorable prognosis if removed early, patients with advanced tumor stages have a low survival rate. These facts highlight the importance of understanding UCEC biology. Computational analysis of RNA-sequencing data from UCEC patients revealed that the molecular motor Myosin Vb (MYO5B) was elevated in the beginning stages of UCEC and occurred in all patients regardless of tumor stage, tumor type, age, menopause status or ethnicity. Although several mutations were identified in the MYO5B gene in UCEC patients, these mutations did not correlate with mRNA expression. Examination of MYO5B methylation revealed that UCEC patients had undermethylated MYO5B and undermethylation was positively correlated with increased mRNA and protein levels. Immunostaining confirmed elevated levels of apical MYO5B in UCEC patients compared to adjacent tissue. UCEC patients with high expressing MYO5B tumors had far worse prognosis than UCEC patients with low expressing MYO5B tumors, as reflected by survival curves. Metabolic pathway analysis revealed significant alterations in metabolism pathways in UCE patients and key metabolism genes were positively correlated with MYO5B mRNA. These data provide the first evidence that MYO5B may participate in UCEC tumor development.