Journal: |
Indian Journal of Pathology and Microbiology
Wolters Kluwer- Medknow Publicationse 65
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Abstract: |
Background: NOTCH1 pathway activation has been recently described to be
a key player in gastric carcinogenesis, enhance the survival and proliferation
of cancer stem cells (CSCs) and mediate chemoresistance in several
malignancies.
Aim: This study investigated the correlation between NOTCH1
and CSC marker OCT4 (octamer binding transcription factor‑4) expression
and the clinicopathological properties, survival and treatment outcome in
patients with gastric carcinoma (GC) receiving adjuvant chemotherapy.
Materials and Methods: NOTCH1 and OCT4 were immunohistochemically
detected in 50 post‑operated specimens of GC. Patients’ data regarding
disease‑free survival (DFS), overall survival (OS), and the response to the
chemotherapy was statistically analyzed.
Results: NOTCH1 and OCT4overexpression was detected in 60% and 52% of GC tissues, respectively, and that was significantly higher than the rates in adjacent non‑neoplastic gastric mucosa (P < 0.05). A significant correlation was detected between
overexpression of NOTCH1 and OCT4 in GC and aggressive clinicopathological
features; poor differentiation (P = 0.021, P = 0.037, respectively), depth of tumor
invasion (P < 0.001 for both), TNM stage (P < 0.001 for both), lymph node
metastasis (P = 0.002, P = 0.003, respectively) and distant metastasis (P < 0.001
for both). NOTCH1 was positively correlated with OCT4 (P = 0.002). Survival
analysis disclosed that upregulation of NOTCH1 and OCT4 was associated
with worse DFS (P = 0.013, P < 0.001, respectively) and OS (P < 0.001 for
both). Overexpression of NOTCH1 and OCT4 correlated with poor response to
chemotherapy (P = 0.013, P = 0.005, respectively) and worse clinical outcome.
Conclusion: Combined detection of these proteins might disclose even better
predictive value for shorter survival and resistance to chemotherapy
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