首页|胰腺癌组织中KYNU mRNA的表达及其与免疫浸润和预后的相关性研究

胰腺癌组织中KYNU mRNA的表达及其与免疫浸润和预后的相关性研究

Expression of KYNU mRNA in Pancreatic Cancer Tissue and Its Correlation with Immune Infiltration and Prognosis

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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(χ2=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 Rank χ2=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(χ2=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 the differences were significant(Log Rank χ2=4.358,4.273,P = 0.039,0.042).Multivariate COX regression analysis showed that TNM stageⅢ(HR:1.653,95%CI:1.294~1.937),low differentiation(HR:1.671,95%CI:1.284~2.003),lymph node metastasis(HR:1.582,95%CI:1.117~1.896)and KYNU high expression(HR:1.591,95%CI:1.106~1.902)were independent risk factors for pancreatic cancer prognosis(all P<0.05).Conclusion KYNU was highly expressed in pancreatic cancer tissues,which was closely related to immune infiltration and clinical prognosis of pancreatic cancer.It may be a potential biomarker for predicting prognosis of pancreatic cancer.

pancreatic cancerkynureninaseimmune infiltration

夏菊芳、刘洪

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无锡市第五人民医院普外科,江苏无锡 214000

胰腺癌 犬尿氨酸酶 免疫浸润

2024

现代检验医学杂志
陕西省临床检验中心,陕西省人民医院

现代检验医学杂志

CSTPCD
影响因子:0.713
ISSN:1671-7414
年,卷(期):2024.39(2)
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