摘要
目的研究犬尿氨酸酶(kynureninase,KYNU)在胰腺癌组织中的表达及其与免疫浸润和预后的关系。方法选取2019年1月~2021年6月于无锡市第五人民医院普外科行手术治疗的49例可切除胰腺癌患者为研究对象,均经病理学及影像学诊断为可切除胰腺癌,肿瘤TNM分期为Ⅰ~Ⅲ期,术前均为接受新辅助治疗,收集其胰腺癌组织和对应癌旁组织(距离癌灶≥4 cm)标本。采用免疫组织化学染色法检测胰腺癌组织及对应的癌旁组织中KYNU蛋白表达及癌组织中CD8^(+)TILs,CD103^(+)TILs,CD68^(+)TAMs,CD204+TAMs和CD11c+DCs浸润情况,实时荧光定量PCR反应检测KYNU mRNA的相对表达量,Pearson相关分析、Kaplan-Meier生存曲线、COX比例风险回归模型分析KYNU mRNA表达与免疫浸润和预后的关系。结果胰腺癌组织中KYNU蛋白阳性率(77.6%)及mRNA表达量(2.9±0.7)显著高于癌旁正常组织(38.8%,0.8±0.5),差异具有统计学意义(χ^(2)=15.138,t=17.088,均P<0.05);KYNU高表达组CD8^(+)TILs,CD103^(+)TILs,CD68^(+)TAMs,CD204+TAMs及CD11c+DCs的浸润数目显著高于KYNU低表达组,差异具有统计学意义(t=2.533~5.806,均P<0.05);胰腺癌中KYNU mRNA表达与CD8^(+)TILs,CD103^(+)TILs,CD68^(+)TAMs,CD204+TAMs及CD11c+DCs的浸润数目呈正相关(r=0.514,0.502,0.319,0.415,0.438,均P<0.05);KYNU高表达组累积OS及累积DFS显著低于KYNU低表达组(20.0%vs 42.9%,14.3%vs 35.7%),差异均有统计学意义(Log Rankχ^(2)=4.358,4.273,P=0.039,0.042)。多因素COX回归分析结果显示,TNM分期Ⅲ期(HR:1.653,95%CI:1.294~1.937)、低分化(HR:1.671,95%CI:1.284~2.003)、淋巴结转移(HR:1.582,95%CI:1.117~1.896)、KYNU高表达(HR:1.591,95%CI:1.106~1.902)是影响胰腺癌预后的独立危险因素(均P<0.05)。结论KYNU在胰腺癌组织中显著高表达,与胰腺癌免疫浸润及临床预后密切相关,可能成为胰腺癌预测预后的潜在生物标志物。
Objective To study the expression of kynureninase(KYNU)in pancreatic cancer tissue and its relationship with immune invasion and prognosis.Methods A total of 49 patients with resectable pancreatic cancer who underwent surgical treatment in Department of General Surgery,Wuxi Fifth People’s Hospital from January 2019 to June 2021 were selected as the study subjects.All patients were diagnosed with resectable pancreatic cancer by pathology and imaging,and their TNM stagings of tumors were stages I-III,which received neoadjuvant therapy before surgery.Cancer tissue and corresponding paracancer tissue samples(≥4cm from the cancer focus)of all patients were collected.Immunohistochemical staining was used to detect the expression of KYNU protein in pancreatic cancer tissues and corresponding adjacent tissues,and the infiltration of CD8^(+)TILs,CD103^(+)TILs,CD68^(+)TAMs,CD204+TAMs,and CD11c+DCs in cancer tissues.Real-time fluorescence quantitative PCR was used to detect the relative expression of KYNU mRNA.The relationship between KYNU mRNA expression and immune infiltration and prognosis was analyzed by Pearson correlation analysis,Kaplan Meier survival curve,and COX proportional hazards regression model.Results The positive rate of KYNU protein(77.6%)and mRNA expression(2.9±0.7)in pancreatic cancer tissues were higher than those in adjacent normal tissues(38.8%,0.8±0.5),and the differences were significant(χ^(2)=15.138,t=17.088,all P<0.05).The infiltration number of CD8^(+)TILs,CD103^(+)TILs,CD68^(+)TAMs,CD204+TAMs and CD11c+DCs in KYNU high expression group was higher than those in KYNU low expression group,and the differences were significant(t=2.533~5.806,all P<0.05).The expression of KYNU in pancreatic cancer was positively correlated with the invasion numbers of CD8^(+)TILs,CD103^(+)TILs,CD68^(+)TAMs,CD204+TAMs and CD11c+DCs(r=0.514,0.502,0.319,0.415,0.438,all P<0.05).The cumulative OS and DFS of high KYNU expression group were lower than those of low KYNU expression group(20.0%vs 42.9%,14.3%vs 35.7%),and
作者
夏菊芳
刘洪
XIA Jufang;LIU Hong(Department of General Surgery,Wuxi Fifth People’s Hospital,Jiangsu Wuxi 214000,China)
出处
《现代检验医学杂志》
CAS
2024年第2期57-61,共5页
Journal of Modern Laboratory Medicine
关键词
胰腺癌
犬尿氨酸酶
免疫浸润
pancreatic cancer
kynureninase
immune infiltration
