RT Journal Article
SR Electronic
T1 WNT Signaling Driven by R-spondin 1 and LGR6 in High-grade Serous Ovarian Cancer
JF Anticancer Research
JO Anticancer Res
FD International Institute of Anticancer Research
SP 6017
OP 6028
DO 10.21873/anticanres.14623
VO 40
IS 11
A1 SANGHOON LEE
A1 JOHN JUN
A1 WILLIAM J. KIM
A1 PABLO TAMAYO
A1 STEPHEN B. HOWELL
YR 2020
UL http://ar.iiarjournals.org/content/40/11/6017.abstract
AB Background/Aim: R-spondins control WNT signaling and RSPO1 and LGR6, two of its receptors, are uniquely expressed at high levels in high-grade serous ovarian cancer (HGSOC). The aim of this study was to assess the interrelations between the expression of the RSPOs and LGRs in HGSOC and in the ovarian surface (OSE) and fallopian tube surface epithelium (FTSE) from which HGSOC arises. Materials and Methods: Analysis of TCGA (HGSOC), CCLE (ovary), and other publicly accessed RNA-Seq data using UC San Diego Computational Cancer Analysis Library (CCAL) to perform differential expression analysis, association studies, and gene set inspection using the single-sample GSEA method. Additionally, we employed multiple publicly available databases including StringDB, Human Protein Atlas, and cBioPortal to aid the investigation. Results: Among normal tissues, expression of RSPO1, LGR5 and LGR6 was highest in the fallopian tube. The relative levels of expression of the RSPOs and LGRs in the OSE and FTSE matched those in HGSOC. RSPO1 and LGR6 were highly co-expressed in all three tissues. Gene set enrichment analysis (GSEA) showed that expression of RSPO1 was strongly linked to the enrichment of three separate WNT-driven GO pathways. Analysis of genes that impacted overall survival identified two other immediately adjacent genes that control WNT signaling, KREMEN1 and ZNRF3 whose expression and copy number were coordinately linked. Conclusion: RSPO1 and LGR6 are coordinately expressed in HGSOC and the two normal tissues from which this tumor arises, and their expression is linked to WNT signaling pathways known the control cell fate and proliferation.