| 摘要: |
| 目的 观察胰腺导管癌组织中法尼醇X受体（FXR）/核因子受体1H4（NR1H4）mRNA和蛋白的表达状况，分析其与患者临床病理特征及预后的关系。方法 选取2013年至2016年海军军医大学（第二军医大学）长海医院胰腺经外科手术切除的胰腺导管腺癌组织标本176例，同时收集患者临床病理资料。将176例胰腺导管腺癌组织标本制作成组织芯片，用RNAscope原位杂交技术和NR1H4探针检测胰腺导管腺癌组织芯片中NR1H4 mRNA的表达，用多聚物二步法的免疫组织化学（IHC）技术检测FXR/NR1H4蛋白的表达。采用χ2检验分析FXR/NR1H4mRNA和蛋白表达与临床病理特征的关系，以Kaplan-Meier生存分析和Cox比例风险回归模型研究FXR/NR1H4mRNA和蛋白表达与预后的关系。结果 176例人胰腺导管腺癌组织中，RNAscope原位杂交技术所测的NR1H4mRNA阳性表达率为68.75%（121/176），IHC技术所测的FXR/NR1H4蛋白阳性表达率为77.27%（136/176）。FXR/NR1H4 mRNA和蛋白表达均与肿瘤临床分期（χ2=5.391，P=0.020；χ2=4.108，P=0.042）、肿瘤分化程度（χ2=6.560，P=0.010；χ2=4.969，P=0.026）有关，蛋白的表达也与肿瘤大小有关（χ2=4.957，P=0.026）；两者与患者性别、年龄、神经浸润、肿瘤部位、淋巴结转移均无关（P均>0.05）。Kaplan-Meier生存分析结果显示，FXR/NR1H4 mRNA和蛋白高表达的患者无进展生存期及总生存期均短于低表达的患者（P均<0.05）。Cox比例风险回归分析结果显示，FXR/NR1H4蛋白高表达为胰腺导管腺癌患者无进展生存期（RR=1.701，95%CI 1.235~2.432，P<0.05）和总生存期（RR=2.356，95%CI 1.983~2.832，P<0.05）的独立危险因素。结论 RNAscope原位杂交技术与IHC技术可以相互印证，保证检测结果的可靠性。胰腺导管腺癌组织中FXR/NR1H4的表达与患者的临床分期和分化程度有关，其高表达是影响患者预后的独立危险因素。 |
| 关键词: 胰腺肿瘤 法尼醇X受体 核因子受体1H4 预后 临床病理特征 原位杂交 RNAscope 免疫组织化学 |
| DOI：10.16781/j.0258-879x.2020.11.1222 |
| 投稿时间：2019-08-07修订日期：2020-02-21 |
| 基金项目:国家自然科学基金面上项目（81672830），海军军医大学（第二军医大学）精准医学转化应用研究专项（2017JZ41）. |
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| Expression of farnesol X receptor in pancreatic ductal adenocarcinoma and its relationship with clinicopathological features and prognosis |
| NI Chen-ming1,NI Can-rong2,ZHENG Kai-lian1,JIN Gang1* |
(1. Department of Hepatobiliary and Pancreatic Surgery, Changhai Hospital, Naval Medical University(Second Military Medical University), Shanghai 200433, China;
2. Department of Pathology, Changhai Hospital, Naval Medical University(Second Military Medical University), Shanghai 200433, China
*Corresponding author) |
| Abstract: |
| Objective To observe the expressions of farnesol X receptor (FXR)/nuclear factor receptor 1H4 (NR1H4) mRNA and protein in pancreatic ductal adenocarcinoma tissues, and to analyze their correlations with clinicopathological features and prognosis. Methods A total of 176 pancreatic ductal adenocarcinoma specimens were collected from Changhai Hospital of Naval Medical University (Second Military Medical University) from 2013 to 2016. The clinicopathological data of the patients were collected. All the specimens were made into tissue microarray. The expression of NR1H4 mRNA was detected by RNAscope in situ hybridization and NR1H4 probe, and FXR/NR1H4 protein was detected by polymer two-step immunohistochemistry. Chi-square test was used to analyze the relationship between the expression levels of FXR/NR1H4 mRNA and protein and clinicopathological features. Kaplan-Meier survival analysis and Cox regression model were used to study the relationship between the expression levels of FXR/NR1H4 mRNA and protein and patient prognosis. Results The positive rate of NR1H4 mRNA detected by RNAscope in situ hybridization was 68.75% (121/176), and that of FXR/NR1H4 protein detected by immunohistochemistry was 77.27% (136/176). FXR/NR1H4 mRNA and protein expression levels were correlated with clinical stage (χ2=5.391, P=0.020; χ2=4.108, P=0.042) and differentiation (χ2=6.560, P=0.010; χ2=4.969, P=0.026); and the protein expression was also related to tumor size (χ2=4.957, P=0.026). No correlations were found between FXR/NR1H4 expression and the patient gender, age, nerve invasion, tumor location or lymph node metastasis (all P>0.05). Kaplan-Meier survival analysis showed that the progression-free survival and overall survival of patients with high expression levels of FXR/NR1H4 mRNA and protein were shorter than those with low expression levels (P<0.05). Cox regression analysis showed that high expression of FXR/NR1H4 protein was an independent risk factor of progressionfree survival (RR=1.701, 95% CI 1.235-2.432, P<0.05) and overall survival of patients (RR=2.356, 95% CI 1.983-2.832, P<0.05). Conclusion RNAscope in situ hybridization and immunohistochemistry can confirm each other to ensure the reliability of the detection results. The expression of FXR/NR1H4 is related to the clinical stage and differentiation of pancreatic ductal adenocarcinoma, and its high expression is an independent risk factor of prognosis. |
| Key words: pancreatic neoplasms farnesol X receptor nuclear factor receptor 1H4 prognosis clinicopathological features in situ hybridization RNAscope immunohistochemistry |
