[1]夏菊芳,刘 洪.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[J].现代检验医学杂志,2024,39(02):57-61.[doi:10.3969/j.issn.1671-7414.2024.02.011]
　XIA Jufang,LIU Hong.Expression of KYNU mRNA in Pancreatic Cancer Tissue and Its Correlation with Immune Infiltration and Prognosis[J].Journal of Modern Laboratory Medicine,2024,39(02):57-61.[doi:10.3969/j.issn.1671-7414.2024.02.011]
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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()
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《现代检验医学杂志》[ISSN:/CN:]

卷:
第39卷
期数:
2024年02期
页码:
57-61
栏目:
论著
出版日期:
2024-03-31

文章信息/Info

Title:
Expression of KYNU mRNA in Pancreatic Cancer Tissue and Its Correlation with Immune Infiltration and Prognosis
文章编号:
1671-7414（2024）02-057-05
作者:
夏菊芳; 刘 洪
（无锡市第五人民医院普外科，江苏无锡 214000）
Author(s):
XIA Jufang;  LIU Hong
（Department of General Surgery, Wuxi Fifth People’s Hospital, Jiangsu Wuxi 214000, China）
关键词:
胰腺癌; 犬尿氨酸酶; 免疫浸润
分类号:
R736.7；R730.43
DOI:
10.3969/j.issn.1671-7414.2024.02.011
文献标志码:
A
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（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 Rankχ2=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。
Abstract:
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 stage Ⅲ (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.

参考文献/References:

[1] 张莉娜, 张霁雯, 罗酩, 等. 胰腺癌组织CTTN 和miR-545-3p 表达水平及其与临床病理和预后的相关性研究[J]. 现代检验医学杂志, 2022, 37(6): 99-103,118. ZHANG Lina, ZHANG Jiwen, LUO Ming, et al. Expression levels of CTTN and miR-545-3p in pancreatic cancer tissues and their correlation with clinicopathology and prognosis[J]. Journal of Modern Laboratory Medicine, 2022, 37(6): 99-103, 118.
[2] MAO Xiaoqi, XU Jin, WANG Wei, et al. Crosstalk between cancer-associated fibroblasts and immune cells in the tumor microenvironment: new findings and future perspectives[J]. Molecular Cancer, 2021, 20(1):131.
[3] 张弛, 严时佳, 万国辉. 色氨酸与肿瘤免疫[J]. 药学学报, 2022, 57(9): 2580-2589. ZHANG Chi, YAN Shijia, WAN Guohui. Tryptophan and tumor immunity[J]. Acta Pharmaceutica Sinica,2022, 57(9): 2580-2589.
[4] AL-MANSOOB M, GUPTA I, STEFAN RUSYNIAK R, et al. KYNU, a novel potential target that underpins CD44-promoted breast tumour cell invasion[J]. Journal of Cellular and Molecular Medicine, 2021, 25(5): 2309-2314.
[5] 李木子, 张豫川, 阿依木古丽·阿不都热依木, 等. 色氨酸及其代谢物对细胞增殖的影响[J]. 中国细胞生物学学报, 2023, 45(7): 1104-1115. LI Muzi, ZHANG Yu c h u a n , AYIMUGULI Abudureyimu, et al. Effects of tryptophan and its metabolites on cell proliferation[J]. Chinese Journal of Cell Biology, 2023, 45(7): 1104-1115.
[6] 白日兰, 崔久嵬. 从肿瘤免疫微环境角度看免疫治疗疗效预测标志物[J]. 中国癌症防治杂志, 2021,13(6): 585-593. BAI Rilan, CUI Jiuwei. Predictors of immunotherapy efficacy from the perspective of tumor immune microenvironment[J]. Chinese Journal of Oncology Prevention and Treatment, 2021, 13(6): 585-593.
[7] BADAWY A A. Tryptophan metabolism and disposition in cancer biology and immunotherapy[J]. Bioscience Reports, 2022, 42(11): BSR20221682.
[8] FAHRMANN J F, TANAKA I, IRAJIZAD E, et al. Mutational activation of the NRF2 pathway upregulates kynureninase resulting in tumor immunosuppression and poor outcome in lung adenocarcinoma[J].Cancers(Basel), 2022, 14(10): 2543.
[9] ZHANG Junwen, WANG Ya’nan, ZHONG Meiling,et al. Kynureninase knockdown inhibits cisplatin resistance in vivo and in vitro and impacts the prognosis of cervical adenocarcinoma[J]. Cell Division, 2023,18(1): 15.
[10] FU Tong, DAI Leijie, WU Songyang, et al. Spatial architecture of the immune microenvironment orchestrates tumor immunity and therapeutic response[J]. Journal of Hematology & Oncology, 2021,14(1): 98.
[11] 任嘉慧, 周云乔, 高鹏翼, 等. 肿瘤浸润淋巴细胞在实体瘤治疗中的研究进展[J]. 中国医药导刊, 2022,24(11): 1062-1067. REN Jiahui, ZHOU Yunqiao, GAO Pengyi, et al. Research progress of tumor-infiltrating lymphocytes in the treatment of solid tumor[J]. Chinese Journal of Medicinal Guide, 2022, 24(11): 1062-1067.
[12] MEHLA K, SINGH P K. Metabolic regulation of macrophage polarization in cancer[J]. Trends Cancer,2019, 5(12): 822-834.
[13] 王建莉, 路小超, 封贺, 等. 树突状细胞与肿瘤免疫系统相互作用研究进展[J]. 生命科学, 2020, 32(2):188-194. WANG Jianli, LU Xiaochao, FENG He, et al. Advances in the study about the role of dendritic cells in tumor immune system[J]. Chinese Bulletin of Life Sciences,2020, 32(2): 188-194.
[14] 高雅媚, 王斌, 李中信, 等. 色氨酸代谢在肿瘤免疫检查点抑制剂治疗中的意义及前景[J]. 肿瘤防治研究, 2021, 48(5): 541-546. GAO Yamei, WANG Bin, LI Zhongxin, et al. Significance and prospect of tryptophan metabolism in the treatment of tumor immune checkpoint inhibitors[J].Cancer Research on Prevention and Treatment, 2021,48(5): 541-546.
[15] YANG Quanjun, HAO Juan, CHI Mengyi, et al. Superior antitumor immunotherapy efficacy of kynureninase modified CAR-T cells through targeting kynurenine metabolism[J]. Oncoimmunology, 2022,11(1): 2055703.

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备注/Memo

备注/Memo:
作者简介：夏菊芳（1985-），女，本科学历，主管护师，研究方向：从事消化肿瘤术后康复治疗，E-mail：157755323@qq.com。
通讯作者：刘洪（1981-），男，硕士，副主任医师，研究方向：主要从事肝胆胃肠肿瘤临床治疗，E-mail：Liu811126@126.com。
更新日期/Last Update: 2024-03-15