Notch3 and Jagged2 contribute to gastric cancer development and to glandular differentiation associated with MUC2 and MUC5AC expression.
OBJECTIVE
Notch signalling plays diverse roles in malignant tumours as well as in normal tissue development. In this study we investigated the expression of Notch signalling pathway genes and their clinicopathological significance in gastric carcinomas.


RESULTS
Notch1, Notch3, Jagged1, Jagged2 and Hes1 expression were analysed by quantitative real-time polymerase chain reaction (qRT-PCR) (n = 81) and immunohistochemistry (n = 103) in gastric carcinomas. MUC2 and MUC5AC expression were also assessed, using immunohistochemistry only. With qRT-PCR, Notch1, Notch3, Jagged1 and Jagged2 expression were increased significantly in tumour compared to normal tissue (P < 0.001, P = 0.002, P = 0.008 and P < 0.001, respectively). Overexpression of Notch3 and Jagged2 was associated with intestinal-type carcinomas (P = 0.024) and better histological differentiation (P = 0.047), respectively. Immunohistochemistry showed a reverse correlation between MUC2 and Notch3 or Jagged1 (P = 0.033 and P = 0.005, respectively) and between MUC5AC and Jagged1 or Hes1 (P = 0.004 and P = 0.002, respectively). Notch3 and Jagged2 gene overexpression related to a favourable outcome on univariate (P = 0.046 and P = 0.042, respectively) and multivariate (P = 0.045, Notch3) analysis.


CONCLUSIONS
The expression of Notch3 and Jagged2 is associated not only with gastric cancer development but also with the intestinal/glandular differentiation of gastric carcinoma cells, suggesting a role as a possible favourable prognostic indicator.
Department of PathologyClinical Research InstituteDepartment of Surgery, CHA Bundang Medical Center, CHA University, Seongnam-si, Gyeonggi-do, Korea.
Haeyoun
H
Kang
Hee-Jung
HJ
An
Ji-Ye
JY
Song
Tae-Heon
TH
Kim
Jin-Hyung
JH
Heo
Dae-Ho
DH
Ahn
Gwangil
G
Kim
D000230:Adenocarcinoma / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism; D015153:Blotting, Western; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis*; D000072101:Jagged-2 Protein; D053208:Kaplan-Meier Estimate; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis*; D008875:Middle Aged; D055271:Mucin 5AC / Q000096:biosynthesis*; D055262:Mucin-2 / Q000096:biosynthesis*; D011379:Prognosis; D060888:Real-Time Polymerase Chain Reaction; D000071656:Receptor, Notch3; D051880:Receptors, Notch / Q000096:biosynthesis*; D013274:Stomach Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D059467:Transcriptome
D014408:Biomarkers, Tumor; D036341:Intercellular Signaling Peptides and Proteins; C490504:JAG2 protein, human; D000072101:Jagged-2 Protein; C524625:MUC2 protein, human; C524678:MUC5AC protein, human; D008565:Membrane Proteins; D055271:Mucin 5AC; D055262:Mucin-2; C499374:NOTCH3 protein, human; D000071656:Receptor, Notch3; D051880:Receptors, Notch