Prognostic significance of Notch 3 gene expression in ovarian serous carcinoma.
The Notch signaling pathway is an important cell signaling system, which regulates cell differentiation, proliferation, and apoptosis, and is aberrantly activated in a wide range of cancer, including ovarian cancers. However, it remains unclear as to whether Notch signaling plays a role in the progression and prognosis of ovarian cancer. We examined the mRNA and protein expression of Notch 3, Jagged 1, and Jagged 2 in 98 ovarian epithelial tumors via real-time PCR and in 175 tumors with immunohistochemical analysis, and then correlated their expression levels with clinicopathological parameters and patient survival. In this study, we detected high levels of Notch3 mRNA and protein expression especially in serous ovarian carcinomas compared to their benign counterparts, accompanied by a positive correlation with the expressions of Jagged 1 and Jagged 2. High levels of Notch 3 mRNA expression (>2-fold than that of benign tumor) were noted in 63% of the serous carcinomas (mean level: 17-fold, P = 0.032). Additionally, Notch 3 protein overexpression was significantly associated with advanced stage (P = 0.0008), lymph node (P = 0.001), and distant metastasis (P = 0.003). Notably, high Notch 3 mRNA and protein expressions were correlated with chemoresistance (P = 0.033) and poor overall survival (P = 0.027, P = 0.042) in these patients. Our results indicate that the Notch 3 signaling pathway is involved in the tumor progression of ovarian serous carcinoma, and higher Notch 3 expression may be an independent poor prognostic factor in this subset of tumors.
Jung
Sang G
SG
Department of Gynecological Oncology, CHA Bundang Medical Center, CHA University, Gyeonggi-do, Korea.
Kwon
Young D
YD
Song
Ji A
JA
Back
Min J
MJ
Lee
Sun Y
SY
Lee
Chan
C
Hwang
Yoon Y
YY
An
Hee J
HJ
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism; D018284:Cystadenocarcinoma, Serous / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry / Q000706:statistics & numerical data; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D000072100:Jagged-1 Protein; D000072101:Jagged-2 Protein; D053208:Kaplan-Meier Estimate; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D011379:Prognosis; D016016:Proportional Hazards Models; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D000071656:Receptor, Notch3; D051880:Receptors, Notch / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000072099:Serrate-Jagged Proteins; D015398:Signal Transduction; D046888:Tissue Array Analysis; D055815:Young Adult
D002135:Calcium-Binding Proteins; D036341:Intercellular Signaling Peptides and Proteins; C000606273:JAG1 protein, human; C490504:JAG2 protein, human; D000072100:Jagged-1 Protein; D000072101:Jagged-2 Protein; D008565:Membrane Proteins; C499374:NOTCH3 protein, human; D012333:RNA, Messenger; D000071656:Receptor, Notch3; D051880:Receptors, Notch; D000072099:Serrate-Jagged Proteins