Expression of stress-induced phosphoprotein1 (STIP1) is associated with tumor progression and poor prognosis in epithelial ovarian cancer.
Stress-induced phosphoprotein1 (STIP1) is a candidate biomarker in epithelial ovarian cancer (EOC). In this study, we investigated in detail the expression of STIP1, as well as its functions, in EOC. STIP1 expression was assessed by immunohistochemistry (IHC) and the results were compared with clinicopathologic factors, including survival data. The effects of STIP1 gene silencing via small interfering RNA (siRNA) were examined in EOC cells and a xenograft model. The expression of STIP1 protein in EOC was significantly higher than in the other study groups (P < 0.001), and this increase of expression was significantly associated with tumor stage (P = 0.005), tumor grade (P = 0.029), and lymph node metastasis (P = 0.020). In multivariate analysis, overall survival in EOC was significantly shorter in cases with high STIP1 expression (HR = 2.78 [1.01-7.63], P = 0.047). STIP1 silencing in EOC cells resulted in inhibition of cell proliferation and invasion. In addition, in vivo experiments using STIP1 siRNA clearly showed a strong inhibition of tumor growth and a modulation of expression of prosurvival and apoptotic genes, further suggesting that STIP1 silencing can prevent cell proliferation and invasion. In conclusion, increased STIP1 expression is associated with poor survival outcome in EOC, and STIP1 may represent a useful therapeutic target in EOC patients.
Department of Obstetrics and Gynecology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea; Institute of Women's Life Medical Science, Yonsei University College of Medicine, Seoul, Korea.
Hanbyoul
H
Cho
Sunghoon
S
Kim
Ha-Yeon
HY
Shin
Eun Joo
EJ
Chung
Haruhisa
H
Kitano
Jae
J
Hyon Park
Lucienne
L
Park
Joon-Yong
JY
Chung
Stephen M
SM
Hewitt
Jae-Hoon
JH
Kim
D000328:Adult; D000368:Aged; D000818:Animals; D000077216:Carcinoma, Ovarian Epithelial; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D018450:Disease Progression; D005260:Female; D006360:Heat-Shock Proteins / Q000235:genetics* / Q000378:metabolism; D064593:Heterografts; D006801:Humans; D051796:Inhibitor of Differentiation Proteins / Q000235:genetics; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000235:genetics; D009375:Neoplasms, Glandular and Epithelial / Q000175:diagnosis* / Q000235:genetics* / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000175:diagnosis* / Q000235:genetics* / Q000378:metabolism; D011379:Prognosis; D051898:Smad1 Protein / Q000378:metabolism; D051902:Smad5 Protein / Q000378:metabolism
D006360:Heat-Shock Proteins; D051796:Inhibitor of Differentiation Proteins; D009363:Neoplasm Proteins; C079373:STIP1 protein, human; D051898:Smad1 Protein; D051902:Smad5 Protein; C075640:ID3 protein, human