Ⅲ期结直肠癌中NLRC3与预后和肿瘤免疫的关系  

Association of NLRC3 with prognosis and tumor immunity in patients with stage Ⅲ colorectal cancer

作　　者：王丹[1] 裴谦 谭风波[1] 周园[1] 王康韬 裴海平[1] WANG Dan;PEI Qian;TAN Fengbo;ZHOU Yuan;WANG Kangtao;PEI Haiping(Department of Gastrointestinal Surgery,Xiangya Hospital,Central South University,Changsha 410008,China)

机构地区：[1]中南大学湘雅医院胃肠外科,长沙410008

出　　处：《中南大学学报（医学版）》2019年第5期535-543,共9页Journal of Central South University ：Medical Science

基　　金：国家自然科学基金(81702956);中南大学战略先导项目(ZLXD2017003);湘雅医院-北大未名临床与康复研究基金(xywm2015I21)~~

摘　　要：目的:探讨核苷酸寡聚化结构域样受体家族半胱天冬酶募集结构域蛋白3(nucleotide binding oligomerization domain-like receptor family caspase recruitment domain containing 3,NLRC3)与Ⅲ期结直肠癌的预后及肿瘤免疫相关指标的关系。方法:回顾性收集中南大学湘雅医院2012年至2013年122例经手术根治切除的Ⅲ期结直肠癌患者的相关资料。利用免疫组织化学法分析NLRC3与CD8^+T细胞的表达情况,利用患者的术前临床资料计算中性粒细胞/淋巴细胞比值(neutrophil to lymphocyte ratio,NLR),并检测其微卫星稳定性。采用χ~2检验分析NLRC3与临床病理因素之间的关系,采用COX回归模型分析Ⅲ期结直肠癌的独立预后因素。结果:在Ⅲ期结直肠癌中,肿瘤组织CD8^+T细胞浸润分期(χ~2=27.79,P<0.01)、NLR值(χ~2=6.35,P<0.05)、淋巴结转移分期(χ~2=10.12,P<0.01)以及微卫星稳定性(χ~2=6.05,P<0.05)与NLRC3的表达有关。NLRC3(OR=0.066,95%CI:0.020～0.218)、血管癌栓(OR=3.119,95%CI:1.547～6.286)及NLR(OR=5.103,95%CI:2.465～10.563)对Ⅲ期结直肠癌的5年总生存期(overall survival,OS)有影响(均P<0.05);另外,NLRC3(OR=0.144,95%CI:0.055-0.377)、血管癌栓(OR=3.589,95%CI:1.859～6.932)及NLR(OR=2.939,95%CI:1.509～5.723)对Ⅲ期结直肠癌的无病生存期(disease free survival,DFS)同样有影响(均P<0.05)。结论:NLRC3,血管癌栓和NLR是Ⅲ期结直肠癌的独立预后因素。NLRC3通过抑制系统性炎症、促进局部抗肿瘤免疫而使Ⅲ期结直肠癌患者具有良好的预后。Objective:To explore the association of nucleotide binding oligomerization domain-like receptor family caspase recruitment domain containing 3(NLRC3)with prognosis and tumor immunity in patients with stageⅢcolorectal cancer.Methods:Data of 122 patients with stageⅢcolorectal cancer,who underwent radical resection from 2012 to 2013 in Xiangya Hospital of Central South University,were retrospectively collected.The expressions of NLRC3 and CD8^+were examined by immumohistochemical(IHC)staining.The preoperative clinical data were used to obtain neutrophil to lymphocyte ratio(NLR),and the stability of microsatellite was determined.The relationship between NLRC3 and clinicopathological factors was analyzed byχ^2 test,and the independent prognostic factors for patients with stageⅢcolorectal cancer were determined by COX regression model.Results:The expression of NLRC3 was significantly associated with CD8^+T cells infiltration(χ^2=27.79,P<0.01),NLR(χ^2=6.35,P<0.05),lymph node metastasis(LN)(χ^2=10.12,P<0.01)and microsatellite stability(χ^2=6.05,P<0.05).NLRC3(OR=0.066,95%CI 0.020 to 0.218),vascular emboli(OR=3.119,95%CI 1.547 to 6.286)and NLR(OR=5.103,95%CI 2.465 to 10.563)had an effect on overall survival(OS)for patients with stageⅢcolorectal cancer(all P<0.05).In addition,NLRC3(OR=0.144,95%CI 0.055 to 0.377),vascular emboli(OR=3.589,95%CI 1.859 to 6.932)and NLR(OR=2.939,95%CI 1.509 to 5.723)also had an effect on disease-free survival(DFS)for patients with stageⅢcolorectal cancer(all P<0.05).Conclusion:NLRC3,intravascular emboli and NLR are independent prognostic factors for patients with stageⅢcolorectal cancer.NLRC3 might be a good prognostic factor for patients with stageⅢcolorectal cancer due to its capacity of inhibiting systemic inflammation and promoting local anti-tumor immunity.

关 键 词：结直肠癌 核苷酸寡聚化结构域样受体家族半胱天冬酶募集结构域蛋白3 血管癌栓 CD8^+T细胞 中性粒细胞/淋巴细胞比值 微卫星稳定性 

分 类 号：R735.34[医药卫生—肿瘤]