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:Tumor Microenvironment Prognostic Risk and Its Association With MUC5AC in Ampullary Carcinoma.
Tumor Microenvironment Prognostic Risk and Its Association With MUC5AC in Ampullary Carcinoma.
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背景.—:肿瘤微环境(TME)中的肿瘤-宿主相互作用影响恶性肿瘤患者的预后。通过肿瘤出芽(BD)和TIL(肿瘤浸润淋巴细胞)评估的TME对非壶腹部小肠癌和结直肠癌患者具有预后影响。在壶腹癌(AC)中,MUC5AC最近被揭示为一个重要的预后因素,但关于TME的研究尚未开展。目的.—:评估AC中基于TME的预后风险。设计.—:我们在64例手术切除的AC中,基于浸润前沿的高级别BD(BD3)和间质TIL高密度(>5%)生成了一个综合TME风险指数。
我们评估了其对总生存期(OS)和无复发生存期(RFS)的预测价值。我们还研究了TME与MUC5AC表达的关系。结果.—:TME预后风险指数分为低风险(BD低/TIL高;64例中26例;41%)、中风险(BD低/TIL低或BD高/TIL高;23例;36%)和高风险(BD高/TIL低;15例;23%)组。较高的TME预后风险与较高的肿瘤分级(P = .03)、淋巴血管侵犯(P = .05)和MUC5AC免疫阳性(P = .02)相关。TME预后风险指数对OS(53.9 vs 46.1 vs 42.2)和RFS(24.8 vs 16.9 vs 15.3)的预测能力均优于单独的BD或TIL。在多变量分析中,TME预后风险指数是OS(P = .003)和RFS(P = .03)的独立预后因素。结论.—:在AC患者中,结合BD和TIL的TME风险指数对OS和RFS的预后风险分层预测均强于单独的BD或TIL。MUC5AC可能调节肿瘤细胞与免疫之间的相互作用,从而增强TME中的侵袭性。
CONTEXT. —: The tumor-host interaction in the tumor microenvironment (TME) affects the prognosis of patients with malignant tumors. TME assessed via tumor budding (BD) and tumor-infiltrating lymphocyte (TIL) had a prognostic impact in patients with nonampullary small intestinal and colorectal carcinomas.
In ampullary carcinoma (AC), MUC5AC was recently revealed as a significant prognosticator, but studies about the TME have not been conducted. OBJECTIVE. —: To assess TME-based prognostic risk in AC. DESIGN. —: We generated a collective TME risk index based on high-grade BD at the invasive front (BD3) and high density of stromal-TIL (>5%) in 64 surgically resected ACs.
We evaluated its predictive values for overall survival (OS) and recurrence-free survival (RFS).
We also investigated the relationship of TME to MUC5AC expression. RESULTS. —: TME prognostic risk index was classified into low-risk (BDLow/TILHigh; 26 of 64; 41%), intermediate-risk (BDLow/TILLow or BDHigh/TILHigh; 23; 36%), and high-risk (BDHigh/TILLow; 15; 23%) groups. Higher TME prognostic risk was associated with higher tumor grade (P = . 03), lymphovascular invasion (P = . 05), and MUC5AC immunopositivity (P = . 02). TME prognostic risk index displayed better predictive ability for both OS (53.
9 versus 46. 1 versus 42. 2) and RFS (24. 8 versus 16. 9 versus 15. 3) than BD or TIL alone. In multivariate analysis, TME prognostic risk index was an independent prognosticator for OS (P = . 003) and RFS (P = . 03). CONCLUSIONS. —: TME risk index in combination with BD and TIL was a stronger predictor of prognostic risk stratification than either BD or TIL alone for both OS and RFS in patients with AC. MUC5AC may modulate the interaction between tumor cells and immunity toward enhancing invasiveness in TME.
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