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循环肿瘤DNA分析用于预测可切除胃癌患者的预后及分子洞察:一项前瞻性研究的结果

Circulating tumor DNA analysis for prediction of prognosis and molecular insights in patients with resectable gastric cancer: results from a prospective study.

作者信息

Liu Zheng, Shi Zhongyi, Jiang Wenchao, Shen Zhenbin, Chen Weidong, Shen Kuntang, Sun Yihong, Tang Zhaoqing, Wang Xuefei

机构信息

Department of Gastrointestinal Surgery Zhongshan Hospital Fudan University Shanghai China.

Gastric Cancer Center Zhongshan Hospital Fudan University Shanghai China.

出版信息

MedComm (2020). 2025 Jan 19;6(2):e70065. doi: 10.1002/mco2.70065. eCollection 2025 Feb.

DOI:10.1002/mco2.70065
PMID:39830022
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11742430/
Abstract

This study aimed to evaluate the prognostic value of plasma circulating tumor DNA (ctDNA) level in patients with resectable gastric cancer (GC). A total of 59 patients were prospectively enrolled, with their ctDNA detected and paired tumor tissue collected at various peri-operative time points. Patients with higher 1-month post-operative ctDNA levels demonstrated shorter overall survival status (hazard ratio [HR] = 5.30,  = 0.0022) and a higher risk of recurrence (HR = 3.85,  = 0.011). The model combining ctDNA with conventional serum tumor markers for GC, including carcinoembryonic antigen, carbohydrate antigen 19-9, and CA72-4, shows high predictive effectiveness for GC prognosis with an area under the curve of 0.940 ( = 0.002), which is higher than net ctDNA and other models without ctDNA. Patients with lower ctDNA levels were more likely to have positive stromal programmed cell death ligand 1 expression ( = 0.046). Additionally, DCAF4L2 mutation was identified as the crucial gene mutation in ctDNA suggesting poor prognosis of patients with GC. Overall, this study highlights that post-operative ctDNA can serve as an effective biomarker for prognostic prediction and recurrence surveillance in resectable GC.

摘要

本研究旨在评估血浆循环肿瘤DNA(ctDNA)水平在可切除胃癌(GC)患者中的预后价值。前瞻性纳入了59例患者,在围手术期的不同时间点检测其ctDNA,并收集配对的肿瘤组织。术后1个月ctDNA水平较高的患者总生存状态较短(风险比[HR]=5.30,P=0.0022),复发风险较高(HR=3.85,P=0.011)。将ctDNA与GC的传统血清肿瘤标志物(包括癌胚抗原、糖类抗原19-9和CA72-4)相结合的模型对GC预后具有较高的预测效能,曲线下面积为0.940(P=0.002),高于单纯ctDNA及其他不含ctDNA的模型。ctDNA水平较低的患者更有可能出现基质程序性细胞死亡配体1表达阳性(P=0.046)。此外,DCAF4L2突变被确定为ctDNA中的关键基因突变,提示GC患者预后不良。总体而言,本研究强调术后ctDNA可作为可切除GC预后预测和复发监测的有效生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1fbd/11742430/a77833950c49/MCO2-6-e70065-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1fbd/11742430/f7a1bc38a806/MCO2-6-e70065-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1fbd/11742430/6bcf7bc4838c/MCO2-6-e70065-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1fbd/11742430/f58e5d241a28/MCO2-6-e70065-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1fbd/11742430/f2affac7a783/MCO2-6-e70065-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1fbd/11742430/a77833950c49/MCO2-6-e70065-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1fbd/11742430/f7a1bc38a806/MCO2-6-e70065-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1fbd/11742430/6bcf7bc4838c/MCO2-6-e70065-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1fbd/11742430/f58e5d241a28/MCO2-6-e70065-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1fbd/11742430/f2affac7a783/MCO2-6-e70065-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1fbd/11742430/a77833950c49/MCO2-6-e70065-g001.jpg

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本文引用的文献

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Molecular residual disease and efficacy of adjuvant chemotherapy in patients with colorectal cancer.结直肠癌患者的分子残留疾病与辅助化疗疗效。
Nat Med. 2023 Jan;29(1):127-134. doi: 10.1038/s41591-022-02115-4. Epub 2023 Jan 16.
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Signatures of EMT, immunosuppression, and inflammation in primary and recurrent human cutaneous squamous cell carcinoma at single-cell resolution.
单细胞分辨率解析原发性和复发性人类皮肤鳞状细胞癌中的 EMT、免疫抑制和炎症特征。
Theranostics. 2022 Oct 31;12(17):7532-7549. doi: 10.7150/thno.77528. eCollection 2022.
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Prognostic and predictive value of a pathomics signature in gastric cancer.胃癌中病理组学特征的预后和预测价值。
Nat Commun. 2022 Nov 12;13(1):6903. doi: 10.1038/s41467-022-34703-w.
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Japanese Gastric Cancer Treatment Guidelines 2021 (6th edition).日本胃癌治疗指南 2021(第 6 版)。
Gastric Cancer. 2023 Jan;26(1):1-25. doi: 10.1007/s10120-022-01331-8. Epub 2022 Nov 7.
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Metastasis Related Epithelial-Mesenchymal Transition Signature Predicts Prognosis and Response to Immunotherapy in Gastric Cancer.转移相关上皮-间充质转化特征可预测胃癌的预后和免疫治疗反应。
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