研究动态
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组织病理学与血浆蛋白水平与结直肠癌诊断后的生存相关。

Histopathology and levels of proteins in plasma associate with survival after colorectal cancer diagnosis.

发表日期:2023 Aug 18
作者: Magnus I Magnusson, Bjarni A Agnarsson, Jon G Jonasson, Thordur Tryggvason, Famke Aeffner, Louise le Roux, Droplaug N Magnusdottir, Helga S Gunnarsdottir, Kristín K Alexíusdóttir, Kristbjorg Gunnarsdottir, Emilia Söebech, Hjaltey Runarsdottir, Erna M Jonsdottir, Bjarney S Kristinsdottir, Sigurgeir Olafsson, Hildur Knutsdottir, Unnur Thorsteinsdottir, Magnus O Ulfarsson, Daniel F Gudbjartsson, Jona Saemundsdottir, Olafur T Magnusson, Gudmundur L Norddahl, J E Vivienne Watson, Thorunn Rafnar, Sigrun H Lund, Kari Stefansson
来源: BRITISH JOURNAL OF CANCER

摘要:

TNM系统被用来评估结直肠癌(CRC)诊断后的预后。其他报道的预后因素包括肿瘤的组织病理学评估、肿瘤突变和血液中的蛋白质。由于其中一些因素之间存在强相关性,因此评估它们对生存的独立影响非常重要。我们对2162名CRC患者的肿瘤样本进行了肿瘤间质数量、瘤边淋巴细胞浸润的严重程度和淋巴滤泡存在与否的视觉评估。对2134个个体的肿瘤进行了体细胞突变评估。对128个个体进行了术前血浆蛋白质水平的测量。我们使用Cox比例风险模型(CPH)检查了这些特征与预后之间的关联。肿瘤间质水平、淋巴细胞浸润和淋巴滤泡的存在都与预后相关,以及高肿瘤突变负荷、高微卫星不稳定性和TP53和BRAF突变。体细胞突变与组织病理学相关,但是在多变量分析中,体细胞突变都与生存率无关。肿瘤间质量和淋巴细胞浸润与肿瘤的局部侵袭相关。两种血浆蛋白CA-125和PPP1R1A的升高与预后较差相关。肿瘤间质和淋巴细胞浸润变量与CRC的预后密切相关,并捕捉到肿瘤突变状态的预后效应。CA-125和PPP1R1A可能是CRC的有用预后生物标志物。© 2023。作者。
The TNM system is used to assess prognosis after colorectal cancer (CRC) diagnosis. Other prognostic factors reported include histopathological assessments of the tumour, tumour mutations and proteins in the blood. As some of these factors are strongly correlated, it is important to evaluate the independent effects they may have on survival.Tumour samples from 2162 CRC patients were visually assessed for amount of tumour stroma, severity of lymphocytic infiltrate at the tumour margins and the presence of lymphoid follicles. Somatic mutations in the tumour were assessed for 2134 individuals. Pre-surgical levels of 4963 plasma proteins were measured in 128 individuals. The associations between these features and prognosis were inspected by a Cox Proportional Hazards Model (CPH).Levels of stroma, lymphocytic infiltration and presence of lymphoid follicles all associate with prognosis, along with high tumour mutation burden, high microsatellite instability and TP53 and BRAF mutations. The somatic mutations are correlated with the histopathology and none of the somatic mutations associate with survival in a multivariate analysis. Amount of stroma and lymphocytic infiltration associate with local invasion of tumours. Elevated levels of two plasma proteins, CA-125 and PPP1R1A, associate with a worse prognosis.Tumour stroma and lymphocytic infiltration variables are strongly associated with prognosis of CRC and capture the prognostic effects of tumour mutation status. CA-125 and PPP1R1A may be useful prognostic biomarkers in CRC.© 2023. The Author(s).