Translational Medicine Research Unit, Medical Research Center Oulu, Oulu University Hospital, and University of Oulu, Oulu, Finland.
Department of Biological and Environmental Science, University of Jyväskylä, Jyväskylä, Finland.
Br J Cancer. 2023 Jun;128(12):2218-2226. doi: 10.1038/s41416-023-02258-2. Epub 2023 Apr 8.
Colorectal cancer (CRC) causes the second most cancer deaths worldwide, but the disease course varies according to tumour characteristics and immunological factors. Our objective was to examine the associations of tumour necrosis with tumour characteristics, immune cell infiltrates, serum cytokine concentrations, as well as prognosis in CRC.
Three independent CRC cohorts, including 1413 patients, were analysed. Associations of the areal percentage of tumour necrosis with clinicopathologic parameters, tumour infiltrating immune cells, cytokine concentrations in systemic and mesenteric vein blood, and survival were examined.
Higher tumour necrosis percentage associated with shorter colorectal cancer-specific survival independent of tumour grade, T, N or M-class, mismatch repair status, BRAF status, and other possible confounding factors. In the largest cohort (N = 1100), the HR for high tumour necrosis percentage (≥40% vs. <3%) was 3.22 (95% CI 1.68-6.17, P < 0.0001). Tumour necrosis percentage positively correlated with peripheral serum levels of CXCL8, a proinflammatory chemokine, and negatively correlated with mesenteric serum levels of CXCL10 and mast cell densities in the invasive margin of the tumour.
Our results support the value of tumour necrosis as a prognostic factor in colorectal cancer. CXCL8 may have a role in the systemic effects of tumour necrosis.
结直肠癌（CRC）是全球导致癌症死亡的第二大主要原因，但疾病的发展过程因肿瘤特征和免疫因素而异。我们的目的是研究肿瘤坏死与肿瘤特征、免疫细胞浸润、血清细胞因子浓度以及 CRC 预后之间的关系。
分析了三个独立的 CRC 队列，共纳入 1413 名患者。分析肿瘤坏死的面积百分比与临床病理参数、肿瘤浸润免疫细胞、全身和肠系膜静脉血中细胞因子浓度以及生存之间的关系。
肿瘤坏死百分比与结直肠癌特异性生存时间缩短独立相关，与肿瘤分级、T、N 或 M 分期、错配修复状态、BRAF 状态以及其他可能的混杂因素无关。在最大的队列（N=1100）中，高肿瘤坏死百分比（≥40%比<3%）的 HR 为 3.22（95%CI 1.68-6.17，P<0.0001）。肿瘤坏死百分比与外周血中 CXCL8（一种促炎趋化因子）的血清水平呈正相关，与肠系膜血中 CXCL10 的血清水平和肿瘤浸润边缘的肥大细胞密度呈负相关。
我们的研究结果支持肿瘤坏死作为结直肠癌预后因素的价值。CXCL8 可能在肿瘤坏死的全身效应中发挥作用。
