长链非编码RNALINC00673和ISG15蛋白在胰腺癌中的表达及其临床意义

Expressions of long non-coding RNA LINC00673 and ISG15 protein in pancreatic cancer and their clinical significances

目的探讨长链非编码RNA LINC00673和ISG15蛋白在胰腺癌组织中的表达情况及其临床意义。方法回顾性分析2014年1月至2018年12月在中南大学湘雅医学院附属肿瘤医院手术切除的经病理诊断为胰腺导管癌(PDAC)的57例患者临床资料。采用定量反转录-聚合酶链反应(qRT-PCR)检测胰腺癌组织和瘤旁正常组织(距癌组织边缘3 cm以内)中LINC00673的相对表达量, 采用免疫组织化学法检测胰腺癌组织和癌旁正常组织中ISG15蛋白的表达情况。比较ISG15蛋白阳性和阴性患者间LINC00673表达差异, 采用Spearman等级相关分析法分析LINC00673和ISG15蛋白表达的相关性, 分析二者与胰腺癌患者临床分期和病理分型的关系。结果胰腺癌组织ISG15蛋白阳性表达率为40.4%(23/57), 高于癌旁正常组织的15.8%(9/57)(χ^(2)=7.90, P=0.004), 胰腺癌组织LINC00673相对表达量为0.99±0.36, 低于癌旁正常组织的1.26±0.41(t=4.80, P<0.001)。ISG15阳性23例(40.4%), ISG15阴性34例(59.7%), ISG15阳性和阴性患者LINC00673的相对表达量分别为0.77±0.46、0.45±0.27(P<0.001)。Spearman法分析显示LINC00673和ISG15蛋白表达有相关性(ρ=-0.429, P=0.001)。低或未分化、血管侵犯、淋巴结转移患者LINC00673相对表达量均降低(均P<0.05), LINC00673相对表达量与患者性别、年龄、肿瘤部位、术前CA199水平、TNM分期均无关(均P>0.05);低或未分化、TNM分期Ⅲ~Ⅳ期、血管侵犯、淋巴结转移患者ISG15蛋白表达水平均升高(均P<0.05), ISG15蛋白表达水平与患者性别、年龄、肿瘤部位和术前CA199水平均无关(均P>0.05)。结论 LINC00673在胰腺癌中的表达与血管侵犯、肿瘤分化程度和淋巴结转移相关, ISG15在胰腺癌中表达与血管侵犯、肿瘤分化程度、淋巴结转移和TNM分期相关。联合检测LINC00673和ISG15蛋白可作为胰腺癌有价值的预后指标。以LINC00673和ISG15蛋白信号通路为靶点的治疗有望成为胰腺癌免疫治疗的潜在方案。

ObjectiveTo explore the expressions of long non-coding RNA LINC00673 and ISG15 protein in pancreatic cancer and their clinical significances.MethodsThe clinical data of 57 patients diagnosed as pancreatic ductal carcinoma(PDAC)at the Affiliated Cancer Hospital of Xiangya Medical College of Central South University from January 2014 to December 2018 were retrospectively analyzed.The relative expressions of LINC00673 in pancreatic cancer tissues and paracancerous normal tissues(within 3 cm from the edge of cancer tissues)were examined by using quantificational reverse transcription-polymerase chain reaction(qRT-PCR).The ISG15 protein expressions in pancreatic cancer tissues and paracancerous normal tissues were examined by using immunohistochemistry.The difference in LINC00673 expression between ISG15 protein positive and negative patients was compared.The correlation between LINC00673 and ISG15 protein expressions in pancreatic cancer was analyzed by Spearman rank correlation analysis.Moreover,the correlations of LINC00673 and ISG15 protein expressions with clinical stage and pathological classification of pancreatic cancer patients were analyzed.ResultsThe positive expression of ISG15 protein in pancreatic cancer tissues was 40.4%(23/57),which was higher than that in paracancerous normal tissues[15.8%(9/57)](χ^(2)=7.90,P=0.004),and the relative expression of LINC00673 in pancreatic cancer tissues was 0.99±0.36,which was lower than that in paracancerous normal tissues(1.26±0.41)(t=4.80,P<0.001).For 23(40.4%)ISG15-positive patients and 34(59.7%)ISG15-negative patients,the relative expression of LINC00673 was 0.77±0.46 and 0.45±0.27(P<0.001).Spearman analysis showed that there was a correlation between LINC00673 and ISG15 protein expressions(ρ=-0.429,P=0.001).The relative expression of LINC00673 decreased in patients with low differentiated or undifferentiated tumor,vascular invasion and lymph node metastasis(all P<0.05),but there was no correlation between LINC00673 expression and patients'age,tumor site,preoperative CA199 level,and TNM stage(all P>0.05);ISG15 protein expression increased in patients with low differentiated or undifferentiated tumor,TNM stageⅢ-Ⅳ,vascular invasion and lymph node metastasis(all P<0.05),but there was no correlation between ISG15 protein expression and patients'gender,age,tumor site,and preoperative CA199 level(all P>0.05).ConclusionsThe expression of LINC00673 in pancreatic cancer is related to vascular invasion,tumor differentiation degree and lymph node metastasis,and the expression of ISG15 in pancreatic cancer is related to vascular invasion,tumor differentiation degree,lymph node metastasis and TNM stage.The combined detection of LINC00673 and ISG15 protein could be a valuable prognostic indicator for pancreatic cancer.The therapies targeting LINC00673 and ISG15 protein signaling pathways are expected to be a potential option for immunotherapy of pancreatic cancer.