NOTCH3基因突变与结直肠癌免疫检查点抑制剂治疗疗效的关联性  

Association of NOTCH3 Mutation with the Prognosis of Colorectal Cancer Patients Treated with Immune Checkpoint Inhibitors

作　　者：李晶[1] 朱静娟[2] 李田军[2] 周娜[2] 张晓春[2] 姜曼[2] 

机构地区：[1]青岛大学,山东 青岛 [2]青岛大学附属医院肿瘤精准医学中心,山东 青岛

出　　处：《临床医学进展》2022年第7期6677-6685,共9页Advances in Clinical Medicine

摘　　要：目的:探讨NOTCH3基因突变与结直肠癌免疫检查点抑制剂治疗疗效的关联性。方法:采用倾向性评分匹配的方法纠正混杂因素的影响,分析NOTCH3基因突变与微卫星不稳定(MSI-H)/超突变状态及免疫检查点抑制剂治疗预后的关联性。结果:55份NOTCH3突变、105份NOTCH3野生型结直肠癌测序样本分析示NOTCH3突变与MSI-H/超突变状态密切关联(关联系数rn = 0.464,P < 0.001)。11例NOTCH3突变、33例NOTCH3野生型晚期结直肠癌患者免疫检查点抑制剂治疗生存分析显示突变患者与野生型患者平均生存期为35.55个月vs 17.03个月(HR = 0.12,95%置信区间0.02~0.88,Log-rank P值 = 0.011)。结论:NOTCH3突变型晚期结直肠癌患者免疫检查点抑制剂治疗后预后更好。Objective: To analyze the correlation between NOTCH3 mutation with the prognosis of colorectal cancer (CRC) patients treated with immune checkpoint inhibitors (ICIs). Methods: Propensity score matching (PSM) adjustment method was applied to reduce the influence of confounding variables to assess the association of NOTCH3 mutation with the status of MSI-H and TMB and evaluate the cor-relation of NOTCH3 mutation with the prognosis of CRC patients treated with ICIs. Results: A total of 55 NOTCH3-mutant and 105 NOTCH3-wildtype colorectal cancer tissues were obtained and demon-strated that NOTCH3 mutation was closely associated with MSI-H/hypermutated status and the as-sociation coefficient (rn) was 0.464 (P < 0.001). Besides, a dataset consisting of 11 NOTCH3-mutant and 33 NOTCH3-wildtype CRC patients treated with ICIs was collected and survival analysis indi-cated that the mean survival time of NOTCH3-mutant CRC patients versus that of NOTCH3-wildtype CRC patients was 35.55 vs. 17.03 months (hazard ratio 0.12;95% CI, 0.02~0.88;Log-rank P = 0.011). Conclusions: NOTCH3-mutant CRC patients had a better prognosis after ICIs therapy.

关 键 词：结直肠癌 免疫检查点抑制剂 NOTCH3基因 生物标志物 倾向性评分匹配 

分 类 号：R735.34[医药卫生—肿瘤]