Department of Pathology, Faculty of Medicine, Zagazig University, Sharkia, Egypt.
Department of Clinical Oncology and Nuclear Medicine, Faculty of Medicine, Zagazig University, Sharkia, Egypt.
Indian J Pathol Microbiol. 2022 Apr-Jun;65(2):328-335. doi: 10.4103/IJPM.IJPM_871_20.
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.
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.
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.
NOTCH1 and OCT4 overexpression 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.
Combined detection of these proteins might disclose even better predictive value for shorter survival and resistance to chemotherapy.
NOTCH1 通路的激活最近被描述为胃癌发生的关键因素，可增强癌症干细胞（CSC）的存活和增殖，并介导多种恶性肿瘤的化疗耐药性。
本研究探讨了 NOTCH1 与 CSC 标志物 OCT4（八聚体结合转录因子-4）表达在接受辅助化疗的胃癌患者中的相关性及其与临床病理特征、生存和治疗结果的关系。
采用免疫组织化学方法检测 50 例胃癌术后标本中 NOTCH1 和 OCT4 的表达。对患者无病生存（DFS）、总生存（OS）和化疗反应的数据进行统计学分析。
GC 组织中 NOTCH1 和 OCT4 的过表达率分别为 60%和 52%，明显高于相邻非肿瘤性胃黏膜（P<0.05）。GC 中 NOTCH1 和 OCT4 的过表达与侵袭性临床病理特征显著相关；低分化（P=0.021，P=0.037）、肿瘤浸润深度（均 P<0.001）、TNM 分期（均 P<0.001）、淋巴结转移（P=0.002，P=0.003）和远处转移（均 P<0.001）。NOTCH1 与 OCT4 呈正相关（P=0.002）。生存分析显示，NOTCH1 和 OCT4 的上调与较差的 DFS（P=0.013，P<0.001）和 OS（均 P<0.001）相关。NOTCH1 和 OCT4 的过表达与对化疗的不良反应（P=0.013，P=0.005）和较差的临床结局相关。
联合检测这些蛋白可能会揭示出更好的预测价值，以提示较短的生存时间和对化疗的耐药性。
