Synuclein-gamma (SNCG) may be a novel prognostic biomarker in uterine papillary serous carcinoma.
OBJECTIVE
SNCG in breast cancer is a marker for advanced and aggressive disease thereby correlating with a poor prognosis in patients. We set out to determine if SNCG expression in UPSC correlates with aggressive cellular properties, poor prognosis, and chemoresistance, and if silencing SNCG can reverse these attributes in vitro.


METHODS
A focused, real time PCR array was performed comparing a papillary serous (SPEC2) and an endometrioid (Ishikawa) endometrial cancer cell line. SNCG was the most differentially expressed gene. SNCG expression was confirmed by real time PCR, Western blot, and immunohistochemistry (IHC) and correlated with outcomes in a pilot set of 20 UPSC patients. A stably transfected SPEC2 cell line was created using shSNCG oligonucleotides. The effect of SNCG knockdown in SPEC2 cells on cell proliferation and sensitivity to paclitaxel-induced apoptosis was measured using a cell viability assay, BrdU incorporation assay, as well as cleaved PARP analyses.


RESULTS
SNCG mRNA as well as protein was highly expressed in SPEC2 cells while minimally to undetectable in several endometrioid endometrial cancer and normal endometrial cell lines. IHC also confirmed unique SNCG expression in UPSC tumors compared to low grade endometrial cancers. In UPSC patients, SNCG expression by IHC correlated with advanced stage and decreased progression-free survival. Knockdown of SNCG in SPEC2 cells caused a significant decrease in cell proliferation and increased sensitivity to paclitaxel-induced apoptosis.


CONCLUSIONS
SNCG is a novel biomarker for aggressive disease and chemoresistance in UPSC and merits further investigation both as a prognostic tool and as a therapeutic target.
Morgan
Jacqueline
J
Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
Hoekstra
Anna V
AV
Chapman-Davis
Eloise
E
Hardt
Jennifer L
JL
Kim
J Julie
JJ
Buttin
Barbara M
BM
D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000235:genetics; D002291:Carcinoma, Papillary / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D048708:Cell Growth Processes / Q000502:physiology; D045744:Cell Line, Tumor; D018284:Cystadenocarcinoma, Serous / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D017239:Paclitaxel / Q000494:pharmacology; D034741:RNA, Small Interfering / Q000235:genetics; D014162:Transfection; D014594:Uterine Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D051845:gamma-Synuclein / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics
D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; D034741:RNA, Small Interfering; C104249:SNCG protein, human; D051845:gamma-Synuclein; D017239:Paclitaxel