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
甲基化 ctDNA、可溶性 PD-L1 与 NK 细胞活性对非小细胞肺癌根治性放疗后复发风险的预后价值
英文原题：The prognostic value of methylated ctDNA, soluble PD-L1, and NK-cell activity on the risk of relapse after curative radiotherapy of non-small cell lung cancer.
查看英文原题
The prognostic value of methylated ctDNA, soluble PD-L1, and NK-cell activity on the risk of relapse after curative radiotherapy of non-small cell lung cancer.
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研究概要
本研究发现，基线时测量的全部六种生物标志物的组合可能有助于预测肺癌根治性 RT 后的复发风险。需要更大规模、随访时间更长的研究来进一步验证这些结果。
研究思路结论见上方概要
背景
尽管接受了根治性放疗（RT）治疗局限性肺癌，但可能在第一年内复发，且5年生存率较低。在本研究中，我们评估了NK 细胞活性（NKA）、可溶性程序性死亡配体1（sPD-L1）和循环肿瘤DNA（ctDNA）联合预测12个月随访内复发的预后能力。
方法
68例患者在基线、首次随访以及治疗后6个月和9个月时进行了血液样本分析。NKA采用NKVue检测法测定，sPD-L1采用Quantikine ELISA试剂盒测定，ctDNA采用内部开发的肿瘤不可知液滴数字聚合酶链反应（ddPCR）检测法测定，用于检测HOXA9、TFAP2B、MCIDAS和SP9基因附近的甲基化位点。单个标志物采用卡方统计或Fisher精确检验，联合标志物采用ROC分析。
结果
基线NKA降低与12个月随访内发生复发显著相关（p = 0.01）。基线ctDNA阳性也与12个月随访内发生复发显著相关（p = 0.03）。所有四种ctDNA标志物、sPD-L1和NKA的联合模型在预测12个月随访内复发方面的曲线下面积为0.86（95% CI 0.74-0.98）。
展开英文摘要原文
MATERIALS AND METHODS
Sixty-eight patients had blood samples analyzed from baseline, the first follow-up visit, and 6 and 9 months after treatment. NKA was measured with the NKVue assay, sPD-L1 was measured with the Quantikine ELISA kit, and ctDNA was measured using in-house developed tumor-agnostic droplet digital polymerase chain reaction (ddPCR) assays for testing methylated loci near the genes HOXA9, TFAP2B, MCIDAS, and SP9. Chi 2 statistics or Fisher's exact test was used for individual markers, and ROC analyses were used for the combined markers.
RESULTS
Baseline reduced NKA was significantly associated with experiencing a relapse within 12-month follow-up (p = 0.01). Having a positive baseline ctDNA was also significantly associated with experiencing a relapse within 12-month follow-up (p = 0.03). The combination of all four ctDNA markers, sPD-L1, and NKA had an area under the curve of 0.86 (95% CI 0.74-0.98) for predicting a relapse within 12 months of follow-up.
CONCLUSION
Findings from this study suggest that a combination of all six biomarkers measured at baseline may help predict the risk of relapse following curative RT for lung cancer. Larger studies with longer follow-up are needed to further verify the results.
论文信息
- 作者
- Fink TL、Andersen RF、Jacobsen CM、Nederby L、Jørgensen MMA、Kristiansen C、Hansen TS、Wen SWC
- 单位
- Department of Oncology, Lillebaelt Hospital, Vejle, University Hospital of Southern Denmark, 7100, Vejle, Denmark. tlf@rsyd.dk.France
- 期刊
- Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico2026 Sep
- 原文标识
- PubMed 41840317 · DOI 10.1007/s12094-026-04317-5
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