Application of RNA-Seq transcriptome analysis: CD151 is an Invasion/Migration target in all stages of epithelial ovarian cancer

Specifically, we sought candidate invasion/migration targets based on expression levels across all tumors, novelty of expression in EOC, and known function. RNA-Seq analysis revealed the high expression of CD151, a transmembrane protein, across all stages of EOC. Expression was confirmed at both the mRNA and protein levels using RT-PCR and immunohistochemical staining, respectively.In both EOC tumors and normal ovarian surface epithelial cells we demonstrated CD151 to be localized to the membrane and cell-cell junctions in patient-derived and established EOC cell lines. We next evaluated its role in EOC dissemination using two ovarian cancer-derived cell lines with differential levels of CD151 expression. Targeted antibody-mediated and siRNA inhibition or loss of CD151 in SKOV3 and OVCAR5 cell lines effectively inhibited their migration and invasion.Taken together, these findings provide the first proof-of-principle demonstration for a next generation sequencing approach to identifying candidate therapeutic targets and reveal CD151 to play a role in EOC dissemination.Epithelial ovarian cancer (EOC) is the most common cause of gynecologic cancer death and the fifth most lethal cancer among women [1]. Despite a relatively low occurrence rate (1 in 72) compared to other female cancers, the low 5-year survival rate of ~40% translates to greater than 14,000 yearly deaths from ovarian cancer in the United States [1]. One main contributor to the low survival rate is the late stage at which EOC is usually detected: upwards of 80% of EOC is discovered after localized spread. When detected early, the EOC 5-year survival rate is ~90% [2].Beyond earlier diagnosis and detection, the identification of novel therapeutic targets or approaches to overcome chemoresistance is necessary to treat late stage or recurrent disease that will occur even with more sensitive and specific screening and detection methods. Since the introduction of platinum-based drugs as first line chemotherapy