Identification of changes in gene expression after knock down of FOXL2 in patient derived immortal fallopian tube cells [CEL-Seq]

In order to identify specific events that are causatively involved in the metastatic process, we analyzed matched samples from 3 high grade serous ovarian cancer patients by RNA-seq. For each patient we examined samples representing the three cancer states: 1) primary tumor; 2) omentum metastasis (solid metastasis); 3) effusion metastasis. We identified genes differentially expressed between the various states. One of the genes found to be expressed in the primary tumor but not in the omentum or effusion metastasis is FOXL2, a transcription factor known to play a role in ovarian development and function. This change was successfully validated by RT-PCR in both the patients' samples as well as in a set of 27 independent patient samples representing the three cancer states. Knock-down of FOXL2 in patient-derived immortal fallopian tube cells lead to increased proliferation and survival. RNA-seq of the immortal fallopian tube cells after FOXL2 knock-down revealed a pro-metastatic gene expression signature. Our results suggest that FOXL2 is an important tumor suppressor and an inhibitor of ovarian cancer progression. Overall design: mRNA profiling of 2 patient derived immortal fallopian tube cells with and without FOXL2 siRNA by CEL-seq analysis