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Lymphocytic response to tumour and deficient DNA mismatch repair identify subtypes of stage II/III colorectal cancer associated with patient outcomes

机译:淋巴细胞对肿瘤和缺陷的DNA错配修复判断与患者结果相关的II / III结直肠癌阶段的亚型

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摘要

Tumour-infiltrating lymphocyte (TIL) response and deficient DNA mismatch repair (dMMR) are determinants of prognosis in colorectal cancer. Although highly correlated, evidence suggests that these are independent predictors of outcome. However, the prognostic significance of combined TIL/MMR classification and how this compares to the major genomic and transcriptomic subtypes remain unclear.A prospective cohort of 1265 patients with stage II/III cancer was examined for TIL/MMR status and Tumours were categorised into four subtypes based on TIL and MMR status: TIL-low/proficient-MMR (pMMR) (61.3% of cases), TIL-high/pMMR (14.8%), TIL-low/dMMR (8.6%) and TIL-high/dMMR (15.2%). Compared with TIL-high/dMMR tumours with the most favourable prognosis, both TIL-low/dMMR (HR=3.53; 95% CI=1.88 to 6.64; PwtwtmutwtwtmutTIL/MMR classification identified subtypes of stage II/III colorectal cancer associated with different outcomes. Although dMMR status is generally considered a marker of good prognosis, we found this to be dependent on the presence of TILs. Prognostication based on TIL/MMR subtypes was superior compared with histopathological, genomic and transcriptomic subtypes.
机译:肿瘤浸润淋巴细胞(TIL)反应和缺陷的DNA错配修复(DMMR)是结直肠癌预后的决定因素。虽然高度相关,但证据表明这些是独立预测的结果。然而,联合TIL / MMR分类的预后意义以及如何与主要基因组和转录组族亚型相比仍然不清楚。检查1265例II / III患者的前瞻性队列,针对TIL / MMR状态检查,肿瘤分为四个基于TIL和MMR状态的亚型:TIL-LOW /易于MMR(PMMR)(61.3%的病例),TIL-HIGH / PMMR(14.8%),TIL-LOW / DMMR(8.6%)和TIL-HIGH / DMMR (15.2%)。与TIL-HIGH / DMMR肿瘤相比,具有最有利的预后,TIL-LOW / DMMR(HR = 3.53; 95%CI = 1.88至6.64; PWTWTMUTWTWTMUTTIL / MMR分类确定了与不同结果相关的II / III结直肠癌的亚型。虽然DMMR状态通常被认为是良好预后的标志,但我们发现这是依赖于直达的存在。与组织病理学,基因组和转录组亚型相比,基于TIL / MMR亚型的预测优越。

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