An integrated analysis of lymphocytic reaction, tumour molecular characteristics and patient survival in colorectal cancer
An integrated analysis of lymphocytic reaction, tumour molecular characteristics and patient survival in colorectal cancer
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DOI：
10.1038/s41416-020-0780-3
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发表时间：
2020-03-11
影响因子：
8.8
通讯作者：
Ogino, Shuji
中科院分区：
文献类型：
--
作者：
Haruki, Koichiro;Kosumi, Keisuke;Ogino, Shuji
背景组织学淋巴细胞反应被认为是结直肠癌独立的预后指标。考虑到缺乏足够的统计能力，调整选择偏倚和全面的肿瘤分子数据在大多数以前的研究中，我们调查了结直肠癌淋巴细胞反应的预后相关性的优势，利用两个前瞻性队列研究的综合数据库。方法对1465例大肠癌患者进行了克罗恩样反应、瘤内、瘤周反应及肿瘤浸润淋巴细胞的检测。共使用4420例结直肠癌病例的协变量数据，使用逆概率加权考克斯比例风险回归模型控制选择偏倚（由于组织可用性）和潜在混杂因素，包括分期、MSI状态、LINE-1甲基化、PTGS 2和CTNNB 1表达、KRAS、BRAF和PIK 3CA突变以及肿瘤新抗原负荷。结果每种淋巴细胞反应成分的水平越高，结直肠癌特异性生存率越高（P趋势< 0.002）。与阴性/低度肿瘤内腺周反应病例相比，中度反应病例的多变量校正HR为0.55（95%CI，0.42-0.71），高度反应病例的多变量校正HR为0.20（95%CI，0.12-0.35）。这些关系在MSI状态或新抗原负荷的分层中是一致的（P-相互作用> 0.2）。结论四种淋巴细胞反应成分可作为结直肠癌的预后指标。
Background Histological lymphocytic reaction is regarded as an independent prognostic marker in colorectal cancer. Considering the lack of adequate statistical power, adjustment for selection bias and comprehensive tumour molecular data in most previous studies, we investigated the strengths of the prognostic associations of lymphocytic reaction in colorectal carcinoma by utilising an integrative database of two prospective cohort studies. Methods We examined Crohn's-like reaction, intratumoural periglandular reaction, peritumoural reaction and tumour-infiltrating lymphocytes in 1465 colorectal carcinoma cases. Using covariate data of 4420 colorectal cancer cases in total, inverse probability-weighted Cox proportional hazard regression model was used to control for selection bias (due to tissue availability) and potential confounders, including stage, MSI status, LINE-1 methylation, PTGS2 and CTNNB1 expression, KRAS, BRAF and PIK3CA mutations, and tumour neoantigen load. Results Higher levels of each lymphocytic reaction component were associated with better colorectal cancer-specific survival (P-trend < 0.002). Compared with cases with negative/low intratumoural periglandular reaction, multivariable-adjusted HRs were 0.55 (95% CI, 0.42-0.71) in cases with intermediate reaction and 0.20 (95% CI, 0.12-0.35) in cases with high reaction. These relationships were consistent in strata of MSI status or neoantigen loads (P-interaction > 0.2). Conclusions The four lymphocytic reaction components are prognostic biomarkers in colorectal carcinoma.