[关键词]
[摘要]
[摘 要] 目的:探究 CD133(又称 PROM1)在胰腺癌组织中的表达及其与患者临床病理特征和预后的关系。方法:采用 GEPIA网站分析TCGA数据库中胰腺癌患者CD133的表达情况,基于TCGA数据库分析人胰腺癌组织中PROM1 mRNA表达与 肿瘤干细胞家族基因的相关性。利用免疫组织化学(IHC)染色技术研究 CD133 在胰腺癌组织中的表达及其临床意义,采用 Wilcoxon秩和检验分析胰腺癌组织及其癌旁组织中CD133表达水平的差异,以χ2 检验分析胰腺癌组织中CD133的表达与临床病 理特征之间的关系,利用Kaplan-Meier法及Log-rank检验分析CD133不同表达水平的生存差异,以拟合Cox模型评价不同指标 的预后价值。采用风险比(HR)及 95% 置信区间(95%CI)评估 CD133 表达水平与胰腺癌患者死亡风险的关联强度。结果: TCGA数据库分析显示,与癌旁组织相比,CD133在胰腺癌组织中的表达显著上调(P < 0.05)。胰腺癌组织中PROM1mRNA表达 水平与肿瘤干细胞家族EPCAM、POU5F1、CD24、CD44和CXCR4相关;在不同分化程度、TNM分期和淋巴结转移情况的胰腺癌 组织中,CD133的表达水平差异均有统计学意义(均P < 0.05);单因素Cox模型分析显示,OS率在胰腺癌患者年龄[HR = 0.544, 95% C(I 0.299,0.990),P < 0.05]、浸润深度[HR = 0.496,95% C(I 0.292,0.842),P < 0.05]、TNM 分期[HR = 2.148,95% C(I 1.352, 3.412),P < 0.05]、CD133表达[HR = 1.935,95% C(I 1.090,3.433),P < 0.05]等方面的差异均有统计学意义。多因素Cox模型分析 显示,患者 TNM 分期[HR = 0.116,95%C(I 0.025,0.551),P < 0.05]、淋巴结转移[HR = 0.392,95%C(I 0.160,0.960),P < 0.05]和 CD133表达[HR = 2.080,95%C(I 1.053,4.106),P < 0.05]可作为预后评估的独立危险因素。结论:胰腺癌组织中CD133呈高表 达,且CD133表达与胰腺癌患者的预后显著相关,是胰腺癌免疫治疗的潜在新靶点。
[Key word]
[Abstract]
[Abstract] Objective: To investigate the expression of CD133 (also known as PROM1) in pancreatic cancer tissues and its association with clinicopathological features and prognosis of pancreatic cancer patients. Methods: The GEPIA website was used to analyze the expression of CD133 in pancreatic cancer patients from the TCGA database. The correlation between PROM1 mRNA expression and cancer stem cell family genes in human pancreatic cancer tissues was analyzed based on the TCGA database. The expression of CD133 in pancreatic cancer tissues and its clinical significance were studied by immunohistochemistry (IHC) staining. Wilcoxon rank sum test was used to analyze the difference in CD133 expression between pancreatic cancer tissues and adjacent tissues. Chi-square test was used to analyze the relationship between CD133 expression and clinicopathological characteristics in pancreatic cancer tissues. KaplanMeier method and Log-rank test were used to analyze the survival difference based on different levels of CD133 expression in pancreatic cancer tissues. The Cox model was used to evaluate the prognostic value of different indicators. Hazard ratio (HR) and 95% confidence interval (95% CI) were used to assess the strength of the association between CD133 expression and mortality risk in pancreatic cancer patients. Results: TCGA database analysis showed that the expression of CD133 was significantly up-regulated in pancreatic cancer tissues compared with adjacent tissues (P < 0.05). The mRNA expression level of PROM1 in pancreatic cancer tissues was correlated with tumor stem cell family genes, including EPCAM, POU5F1, CD24, CD44 and CXCR4. The expression level of CD133 in pancreatic cancer tissues was significantly associated with tumor differentiation, TNM stage, and lymph node metastasis (all P < 0.05). Univariate Cox model analysis showed that overall survival (OS) was significantly associated with age (HR = 0.544, 95%CI [0.299, 0.990], P < 0.05), depth of invasion (HR = 0.496, 95%CI [0.292, 0.842], P < 0.05), TNM stage (HR = 2.148, 95%CI [1.352,3.412], P < 0.05), and CD133 expression (HR = 1.935, 95%CI [1.090, 3.433], P < 0.05). Multivariate Cox model analysis showed that TNM stage (HR = 0.116, 95%CI [0.025, 0.551], P < 0.05), lymph node metastasis (HR = 0.392, 95%CI [0.160, 0.960], P < 0.05) and CD133 expression (HR = 2.080, 95%CI [1.053, 4.106], P < 0.05) were independent prognostic risk factors. Conclusion: CD133 is highly expressed in pancreatic cancer tissues, and its expression is significantly associated with the prognosis of pancreatic cancer patients. CD133 may serve as a potential new target for immunotherapy in pancreatic cancer.
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[基金项目]
国家自然科学基金(No.32270955);江苏省重点研发计划项目(No.BE2022719);江苏省中医药科技发展计划项目(No.ZT202115); 江苏省自然科学基金(No.BK20211065);常州市“十四五”卫生健康高层次人才培养工程(No. 常卫科教[2022]260号);常州市临床医学中心 (No.常卫科教[2022]261号)