Application of circulating tumor DNA detection in the diagnosis and treatment of gastric cancer

doi:10.3969/j.issn.1673-8640.2022.09.017

Abstract

Abstract:

Gastric cancer is one of the most common malignant tumors in the world. Due to its high heterogeneity,the 5-year survival rate is <30%. In the future,it is needed to find new and reliable biological indicators to improve the early diagnosis rate and the prediction accuracy of recurrence and metastasis of gastric cancer,so as to guide the treatment and improve the prognosis. Circulating tumor DNA（ctDNA） is a kind of free DNA released from apoptotic and necrotic tumor cells,which carries the mutation information related to tumor. The ctDNA was usually determined by liquid biopsies. It can be used as a biomarker for the dynamic monitoring of gastric cancer. It is safe,minimally invasive,convenient and repeatable. It has clinical significance in early diagnosis,disease monitoring and individualized treatment. This review expounds the biological characteristics,detection methods and the role of ctDNA in the diagnosis,treatment and prognosis evaluation of gastric cancer,and it discusses the clinical application value of ctDNA in gastric cancer.

Key words: Circulating tumor DNA, Gastric cancer, Biomarker, Liquid biopsy

CLC Number:

R446.7

WANG Rui, LI Zhaoyan, ZHAO Aiguang. Application of circulating tumor DNA detection in the diagnosis and treatment of gastric cancer[J]. Laboratory Medicine, 2022, 37(9): 877-881.

Figures/Tables 1

References 37

[1]	CHEN W, ZHENG R, BAADE P D, et al. Cancer statistics in China,2015[J]. CA Cancer J Clin, 2016, 66(2):115-132. DOI URL
[2]	BRAY F, FERLAY J, SOERJOMATARAM I, et al. Global cancer statistics 2018:GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin, 2018, 68(6):394-424. DOI URL
[3]	ZHENG R, ZENG H, ZHANG S, et al. Estimates of cancer incidence and mortality in China,2013[J]. Chin J Cancer, 2017, 36(1):66. DOI URL
[4]	常敏, 张久聪, 周琴, 等. 胃癌流行病学研究进展[J]. 胃肠病学和肝病学杂志, 2017, 26(9):966-969.
[5]	WARTON K, SAMIMI G. Methylation of cell-free circulating DNA in the diagnosis of cancer[J]. Front Mol Biosci, 2015, 2:13. DOI PMID
[6]	YANG S, TALBI A, WANG X, et al. Pharmacokinetics study of calf thymus DNA in rats and beagle dogs with(3)H-labeling and tracing method[J]. J Pharm Biomed Anal, 2014, 88:60-65. DOI URL
[7]	BRONKHORST A J, UNGERER V, HOLDENRIEDER S. The emerging role of cell-free DNA as a molecular marker for cancer management[J]. Biomol Detect Quantif, 2019, 17:100087.
[8]	KUSTANOVICH A, SCHWARTZ R, PERETZ T, et al. Life and death of circulating cell-free DNA[J]. Cancer Biol Ther, 2019, 20(8):1057-1067. DOI PMID
[9]	ZHOU J, CHANG L, GUAN Y, et al. Application of circulating tumor DNA as a non-invasive tool for monitoring the progression of colorectal cancer[J]. PLoS One, 2016, 11(7):e0159708. DOI URL
[10]	高明正, 张瑾, 潘云, 等. 循环肿瘤DNA研究进展及其临床应用现状[J]. 实用医药杂志, 2019, 36(7):664-668.
[11]	PERKINS G, LU H, GARLAN F, et al. Droplet-based digital PCR:application in cancer research[J]. Adv Clin Chem, 2017, 79:43-91.
[12]	MERKER J D, OXNARD G R, COMPTON C, et al. Circulating tumor DNA analysis in patients with cancer:American Society of Clinical Oncology and College of American Pathologists joint review[J]. J Clin Oncol, 2018, 36(16):1631-1641.
[13]	DEANS Z C, BUTLER R, CHEETHAM M, et al. IQN path ASBL report from the first European cfDNA consensus meeting:expert opinion on the minimal requirements for clinical ctDNA testing[J]. Virchows Arch, 2019, 474(6):681-689. DOI URL
[14]	COHEN J D, LI L, WANG Y, et al. Detection and localization of surgically resectable cancers with a multi-analyte blood test[J]. Science, 2018, 359(6378):926-930. DOI PMID
[15]	LI Q, WU R, WU F, et al. KMT2D promotes proliferation of gastric cancer cells:evidence from ctDNA sequencing[J]. J Clin Lab Anal, 2021, 35(4):e23721.
[16]	GAO Y, ZHANG K, XI H, et al. Diagnostic and prognostic value of circulating tumor DNA in gastric cancer:a meta-analysis[J]. Oncotarget, 2017, 8(4):6330-6340. DOI URL
[17]	LING Z Q, LV P, LU X X, et al. Circulating methylated XAF1 DNA indicates poor prognosis for gastric cancer[J]. PLoS One, 2013, 8(6):e67195. DOI URL
[18]	UCHÔA GUIMARÃES C T, FERREIRA MARTINS N N, CRISTINA DA SILVA OLIVEIRA K, et al. Liquid biopsy provides new insights into gastric cancer[J]. Oncotarget, 2018, 9(19):15144-15156. DOI PMID
[19]	CHEN M, ZHAO H. Next-generation sequencing in liquid biopsy:cancer screening and early detection[J]. Hum Genomics, 2019, 13(1):34. DOI URL
[20]	QIU M Z, LI Q, WANG Z Q, et al. HER2-positive patients receiving trastuzumab treatment have a comparable prognosis with HER2-negative advanced gastric cancer patients:a prospective cohort observation[J]. Int J Cancer, 2014, 134(10):2468-2477. DOI URL
[21]	SHODA K, ICHIKAWA D, FUJITA Y, et al. Monitoring the HER2 copy number status in circulating tumor DNA by droplet digital PCR in patients with gastric cancer[J]. Gastric Cancer, 2017, 20(1):126-135. DOI PMID
[22]	WANG D S, LIU Z X, LU Y X, et al. Liquid biopsies to track trastuzumab resistance in metastatic HER2-positive gastric cancer[J]. Gut, 2019, 68(7):1152-1161. DOI URL
[23]	PECTASIDES E, STACHLER M D, DERKS S, et al. Genomic heterogeneity as a barrier to precision medicine in gastroesophageal adenocarcinoma[J]. Cancer Discov, 2018, 8(1):37-48. DOI PMID
[24]	LIU Y, YANG M, JIANG T, et al. Quantitative analysis of HER2 amplification by droplet digital PCR in the follow-up of gastric cancer patients being treated with trastuzumab after surgery[J]. Gastroenterol Res Pract, 2019, 2019:1750329.
[25]	AGUILAR-MAHECHA A, JOSEPH S, CAVALLONE L, et al. Precision medicine tools to guide therapy and monitor response to treatment in a HER-2+ gastric cancer patient:case report[J]. Front Oncol, 2019, 9:698. DOI URL
[26]	JIN Y, CHEN D L, WANG F, et al. The predicting role of circulating tumor DNA landscape in gastric cancer patients treated with immune checkpoint inhibitors[J]. Mol Cancer, 2020, 19(1):154. DOI PMID
[27]	WANG Y, ZHAO C, CHANG L, et al. Circulating tumor DNA analyses predict progressive disease and indicate trastuzumab-resistant mechanism in advanced gastric cancer[J]. EBioMedicine, 2019, 43:261-269. DOI PMID
[28]	SHAHJEHAN F, KAMATHAM S, KASI P M. Role of circulating tumor DNA in gastrointestinal cancers:update from abstracts and sessions at ASCO 2018[J]. Front Oncol, 2019, 9:358. DOI URL
[29]	DU J, WU X, TONG X, et al. Circulating tumor DNA profiling by next generation sequencing reveals heterogeneity of crizotinib resistance mechanisms in a gastric cancer patient with MET amplification[J]. Oncotarget, 2017, 8(16):26281-26287. DOI PMID
[30]	ZHANG C, CHEN Z, CHONG X, et al. Clinical implications of plasma ctDNA features and dynamics in gastric cancer treated with HER2-targeted therapies[J]. Clin Transl Med, 2020, 10(8):e254. DOI PMID
[31]	KIM Y W, KIM Y H, SONG Y, et al. Monitoring circulating tumor DNA by analyzing personalized cancer-specific rearrangements to detect recurrence in gastric cancer[J]. Exp Mol Med, 2019, 51(8):1-10.
[32]	LI J, LI Z, DING Y, et al. TP53 mutation and MET amplification in circulating tumor DNA analysis predict disease progression in patients with advanced gastric cancer[J]. PeerJ, 2021, 9:e11146. DOI URL
[33]	MATHAI R A, VIDYA R V S, REDDY B S, et al. Potential utility of liquid biopsy as a diagnostic and prognostic tool for the assessment of solid tumors:implications in the precision oncology[J]. J Clin Med, 2019, 8(3):373. DOI URL
[34]	KINUGASA H, NOUSO K, TANAKA T, et al. Droplet digital PCR measurement of HER2 in patients with gastric cancer[J]. Br J Cancer, 2015, 112(10):1652-1655. DOI URL
[35]	KWAK E L, AHRONIAN L G, SIRAVEGNA G, et al. Molecular heterogeneity and receptor coamplification drive resistance to targeted therapy in MET-amplified esophagogastric cancer[J]. Cancer Discov, 2015, 5(12):1271-1281. DOI PMID
[36]	ROLFO C, CARDONA A F, CRISTOFANILLI M, et al. Challenges and opportunities of cfDNA analysis implementation in clinical practice:perspective of the International Society of Liquid Biopsy(ISLB)[J]. Crit Rev Oncol Hematol, 2020, 151:102978. DOI URL
[37]	MARTIGNANO F. Cell-free DNA: an overview of sample types and isolation procedures[J]. Methods Mol Biol, 2019, 1909:13-27. DOI PMID

年份	文献	胃癌组/例	对照组/例	样本来源	变异方式	检测技术	突变基因	临床用途
2015年	MARTIGNANO等^[34]	60	30	血浆	突变	Droplet digital PCR	HER-2	治疗标志物
2015年	KWAK等^[35]	1	0	血浆、肿瘤组织	突变	NGS panel	MET	治疗标志物
2019年	MATHAI等^[33]	70	0	血浆、肿瘤组织	突变	NGS panel	HER-2	治疗标志物
2019年	MARTIGNANO等^[37]	277	0	血浆、肿瘤组织	突变	Mass ARRAY	TP53、PIK3CA、ERBB2、KRAS	诊断/预后的生物标志物

年份	文献	胃癌组/例	对照组/例	样本来源	变异方式	检测技术	突变基因	临床用途
2015年	MARTIGNANO等^[34]	60	30	血浆	突变	Droplet digital PCR	HER-2	治疗标志物
2015年	KWAK等^[35]	1	0	血浆、肿瘤组织	突变	NGS panel	MET	治疗标志物
2019年	MATHAI等^[33]	70	0	血浆、肿瘤组织	突变	NGS panel	HER-2	治疗标志物
2019年	MARTIGNANO等^[37]	277	0	血浆、肿瘤组织	突变	Mass ARRAY	TP53、PIK3CA、ERBB2、KRAS	诊断/预后的生物标志物