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III期结直肠癌中NLRC3与预后和肿瘤免疫的关系
引用本文:王丹,裴谦,谭风波,周园,王康韬,裴海平.III期结直肠癌中NLRC3与预后和肿瘤免疫的关系[J].中南大学学报(医学版),2019,44(5):535-543.
作者姓名:王丹  裴谦  谭风波  周园  王康韬  裴海平
作者单位:中南大学湘雅医院胃肠外科,长沙 410008
基金项目: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χ2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(χ2=27.79,P<0.01)、NLR值(χ2=6.35,P<0.05)、淋巴结转移分期(χ2=10.12,P<0.01)以及微卫星稳定性(χ2=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。

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  

Association of NLRC3 with prognosis and tumor immunity in patients with stage III colorectal cancer
WANG Dan,PEI Qian,TAN Fengbo,ZHOU Yuan,WANG Kangtao,PEI Haiping.Association of NLRC3 with prognosis and tumor immunity in patients with stage III colorectal cancer[J].Journal of Central South University (Medical Sciences)Journal of Central South University (Medical Sciences),2019,44(5):535-543.
Authors:WANG Dan  PEI Qian  TAN Fengbo  ZHOU Yuan  WANG Kangtao  PEI Haiping
Institution:Department of Gastrointestinal Surgery, Xiangya Hospital, Central South University, Changsha 410008, China
Abstract:Objective: To explore the association of nucleotide binding oligomerization domain-like receptorfamily caspase recruitment domain containing 3 (NLRC3) with prognosis and tumor immunity in patients with stage III colorectal cancer. Methods: Data of 122 patients with stage III colorectal 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 by χ2 test, and the independent prognostic factors for patients with stage III colorectal cancer were determined by COX regression model. Results: The expression of NLRC3 was significantly associated with CD8+ T cells infiltration (χ2=27.79, P<0.01), NLR (χ2=6.35, P<0.05), lymph node metastasis (LN) (χ2=10.12, P<0.01) and microsatellite stability (χ2=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 stage III colorectal 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 stage III colorectal cancer (all P<0.05). Conclusion: NLRC3, intravascular emboli and NLR are independent prognostic factors for patients with stage III colorectal cancer. NLRC3 might be a good prognostic factor for patients with stage III colorectal cancer due to its capacity of inhibiting systemic inflammation and promoting local anti-tumor immunity.
Keywords:colorectal cancer  nucleotide binding oligomerization domain-like receptor family caspase recruitment domain containing 3  intravascular emboli  CD8+ T lymphocytes  neutrophil to
  lymphocyte ratio  microsatellite instability  
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