RNF43 p.G659fs 通过 PI3K/AKT/mTOR 信号通路和 HLA-E 上调导致 MSI-high 结直肠癌中 NK 细胞功能障碍
RNF43 p.G659fs leads to natural killer cell dysfunction in MSI-high colorectal cancer through PI3K/AKT/mTOR signaling and HLA-E up-regulation.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Construction of a risk score based on the histopathological tumour microenvironment and its prognostic value in primary operable colorectal cancer.
Construction of a risk score based on the histopathological tumour microenvironment and its prognostic value in primary operable colorectal cancer.
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在本研究中,我们开发了一个预后模型,以准确预测可手术 CRC 的疾病进展和死亡率,并指导辅助化疗。
结直肠癌(CRC)的发病率和死亡率在全球范围内不断上升。我们旨在基于组织病理学肿瘤微环境构建一种新的分类系统——风险评分,并评估其在原发性可手术CRC中的预后价值。
纳入2020年1月至2021年9月期间接受根治性切除的I-III期CRC患者。符合条件的患者按1:1比例随机分为训练队列和验证队列。使用所有切除标本的H&E切片评估肿瘤出芽、肿瘤-间质类型、TIL(肿瘤浸润淋巴细胞)和肿瘤-间质比。随后基于这四个组织病理学特征开发风险评分,并分析其预后价值。在训练队列中,与低风险评分患者相比,高风险评分患者的无病生存期(DFS;HR 2.58,95% CI:1.78-3.72,P < 0.001)和总生存期(OS;HR 2.85,95% CI:1.74-4.67,P < 0.001)更短。多因素分析显示,风险评分仍是DFS和OS的独立预后指标。这些发现在验证队列中得到证实。还建立了一个整合所有独立变量的列线图,以预测个体复发风险。
AIMS: The incidence and mortality rates of colorectal cancer (CRC) are increasing worldwide. We aimed to construct a novel classification system, Risk Score, based on the histopathological tumour microenvironment and assess its prognostic value in primary operable CRC. METHODS AND RESULTS: Patients with stage I-III CRC who underwent radical resection between January 2020 and September 2021 were recruited. Eligible patients were randomized in a 1:1 ratio into a training cohort and a validation cohort. Tumour budding, tumour-stromal type, tumour-infiltrating lymphocytes, and tumour-stroma ratio were evaluated using the H&E sections of all excised specimens. The Risk Score was then developed on the basis of these four histopathological features, and its prognostic value was analysed. In the training cohort, patients with a high-Risk Score had shorter disease-free survival (DFS; HR 2.58, 95% CI: 1.78-3.72, P < 0.001) and overall survival (OS; HR 2.85, 95% CI: 1.74-4.67, P < 0.001) compared with those with a low Risk Score. Multivariate analysis revealed that the Risk Score remained an independent prognostic indicator of DFS and OS. These findings were confirmed in the validation cohort. A nomogram integrating all independent variables was also established to predict the individual risk of recurrence. CONCLUSION: In this study, we developed a prognostic model to accurately predict disease progression and mortality in operable CRC and to guide adjuvant chemotherapy.
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