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
CD274（PD-L1）与 CD3+ 淋巴细胞在预测接受新辅助化疗的晚期结直肠癌患者高危风险中的临床作用
英文原题：Clinical role of CD274 (PD-L1) and CD3+ lymphocytes in predicting high risk in advanced colorectal cancer patients receiving neoadjuvant chemotherapy.
查看英文原题
Clinical role of CD274 (PD-L1) and CD3+ lymphocytes in predicting high risk in advanced colorectal cancer patients receiving neoadjuvant chemotherapy.
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中文摘要
肿瘤免疫反应的机制一直是癌症研究的重点。本研究考察CD274（程序性细胞死亡配体1，PD-L1）及CD3+TIL（肿瘤浸润淋巴细胞）对接受新辅助化疗的晚期结直肠癌（CRC）患者预后的临床意义。研究回顾分析了2008年至2018年接受手术的III/IV期CRC患者原发肿瘤标本。PD-L1和CD3+ TIL均与病理T分期（分别p=0.020和p=0.025）、肿瘤分级（p=0.005和p=0.004）、手术切缘阳性（均p=0.001）及微卫星不稳定性（MSI，均p<0.001）等显著相关。两项标志物也均为MSI的独立相关因素（PD-L1：OR=1.84，95% CI 1.27–4.02，p=0.003；CD3+ TIL：OR=1.92，95% CI 1.31–4.35，p=0.008）。
单变量分析显示，PD-L1高表达、CD3+ TIL低水平以及两者并存均与较差的无复发生存期（RFS）和总生存期（OS）相关。多变量分析显示，PD-L1高表达联合CD3+ TIL低水平对较差RFS和OS的预测更佳（RFS HR=2.85，95% CI 1.36–3.84；OS HR=2.74，95% CI 1.32–3.71；均p<0.001）。PD-L1高表达本身也是OS和RFS的独立预后指标。结果提示，在接受化疗的CRC患者中，PD-L1高表达联合CD3+ TIL低水平可可靠预测较差生存，因此这些标志物可能有助于规划和实施适当的靶向治疗。
展开英文摘要原文
In cancer research, the mechanism underlying the immune response to a tumour has been of great interest. In this study, we investigated the role of CD274 (programmed cell death-ligand 1 - PD-L1) and CD3+ tumour-infiltrating lymphocytes (TILs) in the prognosis of advanced colorectal cancer (CRC) patients treated with neoadjuvant chemotherapy.
We retrospectively examined primary tumour specimens from stage III/IV CRC patients operated on between 2008 and 2018.
We found a significant association between these biomarkers and pT stage (PD-L1, p = 0. 020; CD3+TILs, p = 0. 025), tumour grade (PD-L1, p = 0. 005; CD3+TILs, p = 0. 004), positive surgical margin (PD-L1, p = 0. 001; CD3+TILs, p = 0. 001), MSI (PD-L1, p < 0. 001; CD3+TILs, p < 0. 001), etc.
We also discovered that these biomarkers are independent risk factors for MSI (PD-L1, OR = 1. 84 [1. 27-4. 02], p = 0. 003; CD3+TILs, OR = 1. 92 [1. 31-4. 35], p = 0. 008). Univariate analysis results revealed that patients with high PD-L1, low CD3+TIL, and both showed poor relapse-free survival (RFS) and poor overall survival (OS) (PD-L1: RFS, p = 0. 008 and OS, p = 0.
001; CD3+TILs: RFS, p = 0. 003 and OS, p = 0. 005; PD-L1 and CD3+TILs: RFS, p < 0. 001 and OS, p < 0. 001). The results of the multivariate analysis showed that the combined use of high PD-L1 and low CD3+TILs was a better predictor of poor RFS and OS (PD-L1 and CD3+TILs: RFS, hazard ratio - HR, = 2. 85 [95% CI: 1. 36-3. 84], p < 0. 001); OS, HR = 2. 74 [1. 32-3. 71], p < 0. 001).
We also found a high PD-L1 parameter as another independent overall and relapse-free survival parameter.
Our findings suggest that a combination of high PD-L1 and low CD3+TIL can reliably predict poor survival in CRC patients receiving chemotherapy.
Therefore, these biomarkers may be promising for the planning and execution of appropriate targeted therapies.
论文信息
- 作者
- Benek S、Zengin M
- 第一作者单位
- Department of General Surgery, Tekirdağ University, Tekirdağ, Turkey.Turkey
- 通讯作者单位
- Department of Pathology, Ankara Training and Research Hospital, Ankara, Turkey.Turkey
- 期刊
- Polish journal of pathology : official journal of the Polish Society of Pathologists2023
- 原文标识
- PubMed 37728469 · DOI 10.5114/pjp.2023.129520