胃癌高通量测序临床应用中国专家共识

中国抗癌协会胃癌专业委员会

doi:10.12354/j.issn.1000-8179.2023.20230030

胃癌高通量测序临床应用中国专家共识

doi: 10.12354/j.issn.1000-8179.2023.20230030

中国抗癌协会胃癌专业委员会^,

详细信息

通讯作者:
徐惠绵　xuhuimian@126.com

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出版历程
- 收稿日期: 2023-01-09
- 录用日期: 2023-02-28
- 修回日期: 2023-02-16

Chinese expert consensus on the clinical application of next-generation sequencing for gastric cancer

China Anti-Cancer Association Commitee of Gastric Cancer^,

More Information

Corresponding author: Huimian Xu; E-mail: xuhuimian@126.com

摘要

摘要: 胃癌是消化系统最常见的恶性肿瘤之一，异质性较强，具有复杂的分子特征。HER2、MSI、TMB和NTRK融合等肿瘤相关标志物及分子病理学检测革新了胃癌诊疗模式。根据患者的病理特征和基因检测结果进一步筛选靶向和免疫药物的潜在获益人群，是胃癌精准治疗的未来发展方向。高通量测序（next-generation sequencing，NGS）在胃癌诊断、治疗方案选择、预后监测中发挥着日益重要的作用。然而，国内目前对胃癌NGS的理解与应用尚有不足。中国抗癌协会胃癌专业委员会专家组基于循证医学证据制定《胃癌高通量测序临床应用中国专家共识》，旨在提高中国临床医生与患者对于胃癌NGS的认识，以指导与规范其在国内的临床应用。
- 胃癌 /
- 精准诊疗 /
- 高通量测序 /
- 专家共识
Abstract: Gastric cancer is one of the most common malignant tumors in the digestive system, with high heterogeneity and complex molecular characteristics. The emergence of tumor-associated biomarkers, such as HER2, MSI, TMB, and NTRK fusion, and molecular pathological diagnostics have revolutionized the diagnosis and treatment methods of gastric cancer. Screening potential beneficiaries of targeted therapies and immunotherapies based on pathological characteristics and genetic testing results may be a future direction for developing precise treatments for gastric cancer. Next-generation sequencing (NGS) plays an increasingly important role in diagnosing, selecting treatment strategies, and prognostic monitoring of gastric cancer. However, the NGS of gastric cancer remains poorly understood in China. Hence, China Anti-Cancer Association Commitee of Gastric Cancer formulated the Chinese expert consensus on the NGS of gastric cancer based on evidence-based medicine to improve the understanding of clinicians and patients on the NGS of gastric cancer and to guide and standardize its clinical applications in China.
- gastric cancer /
- precise diagnosis and treatment /
- next-generation sequencing (NGS) /
- expert consensus

HTML全文

表 1 共识推荐等级

推荐等级	证据类别标准
Ⅰ级推荐	基于高级别证据，专家组意见高度一致
Ⅱ级推荐	基于高级别证据，专家组意见基本一致
	基于低级别证据，专家组意见高度一致
Ⅲ级推荐	基于低级别证据，专家组意见基本一致
不推荐	专家组存在意见分歧

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表 2 遗传性胃癌筛查基因

证据来源	遗传性疾病类型	筛查基因
van der Post等^[8]	HDGC	CDH1
Sahasrabudhe等^[9]	HDGC	CTNNA1、PALB2、RAD51C
Li等^[10]	GAPPS	APC
Latham等^[12]	LS	MLH1、MSH2、MSH6、PMS2、EPCAM
MacFarland等^[13]	JPS	SMAD4、BMPR1A
Jiang等^[14]	PJS	STK11
Buckley等^[15]	HBOCS	BRCA1、BRCA2
Dinarvand等^[16]	FAP	APC
Aelvoet等^[17]	MAP	MUTYH
2022 V2版NCCN指南（胃癌证据不足）	共济失调毛细血管扩张症	ATM
2022 V2版NCCN指南（胃癌证据不足）	布鲁姆综合征	BLM/RECQL3
2022 V2版NCCN指南（胃癌证据不足）	李-佛美尼综合征	TP53
2022 V2版NCCN指南（胃癌证据不足）	着色性干皮症	7种不同的基因
2022 V2版NCCN指南（胃癌证据不足）	多发性错构瘤综合征	PTEN

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表 3 NTRK融合检测技术特征和优劣势比较

方法	敏感性	特异性	检测NTRK1/2/3	鉴定融合伴侣	确定表达	筛查
IHC	高^a	高^b	是	否	是	是
FISH	高	高	独立探针^c	否	否	否
RNA-based	高	高	是	是	是	是
DNA-based^*	中等	高	是	是	否	是
^a：假阴性主要来源于NTRK3融合；^b：在没有平滑肌/神经元分化的情况下；^c：NTRK基因的3个亚型需要3组探针；^*：通过基于DNA的方法检测到的重排可能不会导致融合表达。

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表 4 基于NGS的胃癌组织和液态分子检测内容和时机

患者分层	标志物	检测意义	样本类型和推荐等级
Ⅰ～Ⅳ期所有患者	ERBB2扩增	抗HER2靶向治疗疗效预测	组织（Ⅱ级）/血液（Ⅱ级）
Ⅰ～Ⅳ期所有患者	MSI-H	LS遗传评估，早期无法化疗获益，晚期ICIs疗效预测	组织（Ⅰ级）
Ⅰ～Ⅲ期术后辅助治疗	MRD	术后复发监测	血液（Ⅲ级）
Ⅱ～Ⅳ期接受化疗的患者	DPYD基因多态性	氟尿嘧啶剂量调整	血液（Ⅲ级）
Ⅱ～Ⅳ期接受化疗的患者	UGT1A1基因多态性	伊立替康剂量调整	血液（Ⅲ级）
晚期患者治疗阶段	ctDNA	疗效预测和耐药评估	血液（Ⅲ级）
标准治疗失败的晚期患者	NTRK1/2/3融合和点突变	NTRK抑制剂靶向治疗疗效和耐药评估	组织（Ⅱ级）
	TMB	晚期患者ICIs治疗疗效预测	组织（Ⅱ级）
	EBV	ICIs治疗潜在获益，分子分型	组织（Ⅲ级）
	POLE/POLD	ICIs治疗正相关	组织（Ⅲ级）
	TP53、B2M、JAK1/2、PTEN	ICIs治疗负相关	组织（Ⅲ级）
	EGFR/MDM2/MDM4扩增、DNMT3A	ICIs治疗超进展	组织（Ⅲ级）
	RTK-RAS-PI3K突变、CCNE1扩增	抗HER2治疗原发继发耐药	组织（Ⅲ级）
	BRAF V600E	BRAF/MEK抑制剂治疗获益	组织（Ⅲ级）
	FGFR2/EGFR/MET扩增、RET/ROS1/ALK融合	TKIs抑制剂疗效预测	组织（Ⅲ级）
	NRG1融合	NRG1抑制剂疗效评估	组织（Ⅲ级）

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