早期胰腺癌分子诊断专家共识（2023年版）

中国医师协会临床精准医疗专业委员会; 中国抗癌协会肿瘤胰腺病学专业委员会

doi:10.12449/JCH240306

早期胰腺癌分子诊断专家共识（2023年版）

DOI: 10.12449/JCH240306

基金项目:

国家自然科学基金 (81770846);

国家自然科学基金 (81642006);

Hirshberg胰腺癌研究基金 (AH201901083);

康德生物癌症研究基金 (KD2021030001)

利益冲突声明：本文不存在任何利益冲突。

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出版历程
- 收稿日期: 2024-01-12
- 录用日期: 2024-02-01
- 出版日期: 2024-03-20

Expert consensus on the molecular diagnosis of early-stage pancreatic cancer （2023 edition）

Research funding:

Natural National Science Foundation of China (81770846);

Natural National Science Foundation of China (81642006);

U.S. Hirshberg Foundation for Pancreatic Cancer Research (AH201901083);

Kante Seeds Grant Foundation for Cancer Research (KD2021030001)

摘要

摘要: 胰腺癌是一种较为常见的消化系统肿瘤，早期诊断困难，恶性程度极高。以肿瘤生物标志物为核心的分子辅助诊断技术，结合现有临床金标准，对于实现早期精准检测、及时治疗干预及降低病死率具有重要的临床意义。研究证实，微小RNA（miRNA）在胰腺肿瘤不同病理时期出现的种类和表达量变化呈现高度特异性，可用于胰腺肿瘤发生、发展的全程监测。单个miRNA的诊断潜力有限，miRNA组合或可有效提升对早期胰腺癌变的诊断性能。本共识基于近年相关研究进展，填补胰腺癌临床诊疗指南中关于分子诊断技术的空白，并提供专家指导意见。
- 胰腺肿瘤 /
- 癌症早期检测 /
- 生物标记，肿瘤 /
- 微RNAs /
- 专家共识
Abstract: Pancreatic cancer is a relatively common tumor of the digestive system， with difficulties in early-stage diagnosis and an extremely high degree of malignancy. Molecular diagnostic technology based on tumor biomarkers， combined with the existing gold standard in clinical practice， is of great clinical significance to achieve early accurate identification， timely treatment and intervention， and reduction in mortality. Previous studies have shown that miRNAs show high specificity in terms of types and expression levels in different pathological stages of pancreatic cancer and can thus be used in monitoring the development and progression of pancreatic cancer. Since a single miRNA has a limited diagnostic potential， the combination of different miRNAs may effectively improve the diagnostic efficiency of early-stage pancreas carcinogenesis. Based on related research advances in recent years， this consensus document aims to fill the gap in molecular diagnostic technology in the guidelines for the clinical diagnosis and treatment of pancreatic cancer and provide expert guidance and recommendations.
- Pancreatic Neoplasms /
- Early Detection of Cancer /
- Biomarkers， Tumor /
- MicroRNAs /
- Expert Consensus

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表 1 GRADE分级系统

Table 1. Grading of recommendations assessment， development and evaluation

类别	分级	定义
证据质量分级	高	非常有把握观察值接近真实值
	中	对观察值有中等把握：观察值有可能接近真实值，但也有可能差别很大
	低	对观察值的把握有限：观察值可能与真实值有很大差别
	极低	对观察值几乎没有把握：观察值与真实值可能有极大差别
推荐强度分级	强	有1项或多项高质量的随机对照研究回答该临床问题
	中	针对该问题，有设计良好的临床研究但样本量小于500
	弱	专家委员会的报告或观点，以及权威专家的临床经验，提示本领域需进行高质量的临床研究

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表 2 胰腺癌高频突变基因

Table 2. High frequency mutant genes of pancreatic cancer

基因	功能	突变频率
KRAS	原癌基因，调控细胞生长分化	>95%
TP53	抑癌基因，细胞凋亡及分化	50%～75%
CDKN2A/p16INK4	抑癌基因，调节细胞周期	95%～98%
DPC4/SMAD4	抑癌基因，参与细胞凋亡	50%
BRCA1	抑癌基因，参与双链DNA的断裂修复	15%
BRCA2	抑癌基因，参与双链DNA的断裂修复	17%
PALB2	抑癌基因，参与双链DNA的断裂修复	5%
注：BRCA，乳腺癌易感基因；PALB2，BRCA2定位协作基因。

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表 3 胰腺癌阳性患者4个miRNA联合检测结果

Table 3. Results of combined detection of 4 miRNAs in pancreatic cancer-positive patients

4个miRNA联合检测	病理学诊断		合计（例）
4个miRNA联合检测	阳性（例）	阴性（例）	合计（例）
阳性（例）	720	26	746
阴性（例）	21	539	560
合计（例）	741	565	1 306

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参考文献(20)

[1]	ZHENG RS, ZHANG SW, ZENG HM, et al. Cancer incidence and mortality in China, 2016[J]. J Natl Cancer Cent, 2022, 2( 1): 1- 9. DOI: 10.1016/j.jncc.2022.02.002.
[2]	KANDA M, MATTHAEI H, WU J, et al. Presence of somatic mutations in most early-stage pancreatic intraepithelial neoplasia[J]. Gastroenterology, 2012, 142( 4): 730- 733. e 9. DOI: 10.1053/j.gastro.2011.12.042.
[3]	MARIN AM, BATISTA M, de AZEVEDO ALK, et al. Screening of exosome-derived proteins and their potential as biomarkers in diagnostic and prognostic for pancreatic cancer[J]. Int J Mol Sci, 2023, 24( 16): 12604. DOI: 10.3390/ijms241612604.
[4]	HANAHAN D, WEINBERG RA. Hallmarks of cancer: The next generation[J]. Cell, 2011, 144( 5): 646- 674. DOI: 10.1016/j.cell.2011.02.013.
[5]	HUANG J, GAO G, GE Y, LIU JZ, et al. Development of a serum-based microRNA signature for early detection of pancreatic cancer: a multicenter cohort study[J]. Dig Dis Sci, 2024.[Forthcoming]
[6]	LI H, CHIANG CL, KWAK KJ, et al. Extracellular vesicular analysis of glypican 1 mRNA and protein for pancreatic cancer diagnosis and prognosis[J]. Adv Sci(Weinh), 2024. DOI: 10.1002/advs.202306373.[ Online ahead of Print]
[7]	KAMAL MA, SIDDIQUI I, BELGIOVINE C, et al. Oncogenic KRAS-induced protein signature in the tumor secretome identifies laminin-C2 and pentraxin-3 as useful biomarkers for the early diagnosis of pancreatic cancer[J]. Cancers(Basel), 2022, 14( 11): 2653. DOI: 10.3390/cancers14112653.
[8]	CAVE DD, BUONAIUTO S, SAINZ B Jr, et al. LAMC2 marks a tumor-initiating cell population with an aggressive signature in pancreatic cancer[J]. J Exp Clin Cancer Res, 2022, 41( 1): 315. DOI: 10.1186/s13046-022-02516-w.
[9]	CHEN XB, LIAO XM, ZHENG BL, et al. Differential plasma proteins identified via iTRAQ-based analysis serve as diagnostic markers of pancreatic ductal adenocarcinoma[J]. Dis Markers, 2023, 2023: 5145152. DOI: 10.1155/2023/5145152.
[10]	LUO XL, LIU JJ, WANG HZ, et al. Metabolomics identified new biomarkers for the precise diagnosis of pancreatic cancer and associated tissue metastasis[J]. Pharmacol Res, 2020, 156: 104805. DOI: 10.1016/j.phrs.2020.104805.
[11]	ZHAO R, REN S, LI CY, et al. Biomarkers for pancreatic cancer based on tissue and serum metabolomics analysis in a multicenter study[J]. Cancer Med, 2023, 12( 4): 5158- 5171. DOI: 10.1002/cam4.5296.
[12]	CAO YY, ZHAO R, GUO K, et al. Potential metabolite biomarkers for early detection of stage-I pancreatic ductal adenocarcinoma[J]. Front Oncol, 2022, 11: 744667. DOI: 10.3389/fonc.2021.744667.
[13]	SAHNI S, PANDYA AR, HADDEN WJ, et al. A unique urinary metabolomic signature for the detection of pancreatic ductal adenocarcinoma[J]. Int J Cancer, 2021, 148( 6): 1508- 1518. DOI: 10.1002/ijc.33368.
[14]	SKUBISZ K, DĄBKOWSKI K, SAMBOROWSKA E, et al. Serum metabolite biomarkers for pancreatic tumors: Neuroendocrine and pancreatic ductal adenocarcinomas-a preliminary study[J]. Cancers(Basel), 2023, 15( 12): 3242. DOI: 10.3390/cancers15123242.
[15]	EISSA MAL, LERNER L, ABDELFATAH E, et al. Promoter methylation of ADAMTS1 and BNC1 as potential biomarkers for early detection of pancreatic cancer in blood[J]. Clin Epigenetics, 2019, 11( 1): 59. DOI: 10.1186/s13148-019-0650-0.
[16]	LI SY, WANG L, ZHAO Q, et al. Genome-wide analysis of cell-free DNA methylation profiling for the early diagnosis of pancreatic cancer[J]. Front Genet, 2020, 11: 596078. DOI: 10.3389/fgene.2020.596078.
[17]	SCHOTT S, YANG RX, STÖCKER S, et al. HYAL2 methylation in peripheral blood as a potential marker for the detection of pancreatic cancer: A case control study[J]. Oncotarget, 2017, 8( 40): 67614- 67625. DOI: 10.18632/oncotarget.18757.
[18]	WU YN, SEUFERT I, AL-SHAHERI FN, et al. DNA-methylation signature accurately differentiates pancreatic cancer from chronic pancreatitis in tissue and plasma[J]. Gut, 2023, 72( 12): 2344- 2353. DOI: 10.1136/gutjnl-2023-330155.
[19]	MAKLER A, ASGHAR W. Exosomal miRNA biomarker panel for pancreatic ductal adenocarcinoma detection in patient plasma: A pilot study[J]. Int J Mol Sci, 2023, 24( 6): 5081. DOI: 10.3390/ijms24065081.
[20]	XIAO D, DONG ZJ, ZHEN LQ, et al. Combined exosomal GPC1, CD82, and serum CA19-9 as multiplex targets: A specific, sensitive, and reproducible detection panel for the diagnosis of pancreatic cancer[J]. Mol Cancer Res, 2020, 18( 2): 300- 310. DOI: 10.1158/1541-7786.MCR-19-0588.