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浙江大学学报（医学版）
J Zhejiang Univ (Med Sci)  2019, Vol. 48 Issue (3): 326-333    DOI: 10.3785/j.issn.1008-9292.2019.06.14
    
Advances in serum biomarkers for early diagnosis of gastric cancer
ZHANG Yunzhu(),ZHU Chunpeng,LU Xinliang*()
Department of Gastroenterology, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China
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Abstract  

Early diagnosis is the key to improve the prognosis of gastric cancer. How to screen out high-risk subjects of gastric cancer in population is a hot spot. Serum-based early detection of gastric cancer is suitable for high-risk population screening, which is more convenient and safer. This article reviews the diagnostic value of serum biomarkers for gastric cancer, including serum DNA methylation, various RNAs, pepsinogen, gastrin, osteopontin, MG7-Ag and CA724. Until now, there is still lack of ideal biomarkers for gastric cancer, and searching for specific RNAs may be promising for early diagnosis and screening of gastric cancer.

Key words： Stomach neoplasms/diagnosis      Stomach neoplasms/blood      Biomarkers, tumor/blood      Early diagnosis      Review     
Received: 14 December 2018      Published: 04 September 2019
CLC:  R446  
  R735.2  
Corresponding Authors: LU Xinliang     E-mail: zyz1109@zju.edu.cn;lux@zju.edu.cn
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ZHANG Yunzhu
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Cite this article:

ZHANG Yunzhu, ZHU Chunpeng, LU Xinliang. Advances in serum biomarkers for early diagnosis of gastric cancer. J Zhejiang Univ (Med Sci), 2019, 48(3): 326-333.

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http://www.zjujournals.com/med/10.3785/j.issn.1008-9292.2019.06.14     OR     http://www.zjujournals.com/med/Y2019/V48/I3/326


胃癌早期诊断的血清生物学标志物研究进展

早期诊断是胃癌患者良好预后的关键，如何在人群中筛查胃癌高危者是当前的一个热点。基于血清的胃癌早期诊断检测适用于高风险人群筛查，更加方便、安全。本文介绍了胃癌的血清生物学标志物的研究进展，包括血清DNA甲基化、各种RNA、胃蛋白酶原、胃泌素、骨桥蛋白、MG7-Ag和CA724等血清生物学标志物在胃癌诊断方面的价值，并指出寻找胃癌特异的RNA是比较有前景的早期诊断和筛查方法。


关键词： 胃肿瘤/诊断,  胃肿瘤/血液,  生物标记, 肿瘤/血液,  早期诊断,  综述 
[1]   王宁, 刘硕, 杨雷 et al. 2018全球癌症统计报告解读[J]. 肿瘤综合治疗电子杂志, 2019, 5 (1): 87- 97
WANG Ning , LIU Shuo , YANG Lei et al. Interpretation on the report of Global Cancer Statistics 2018[J]. Journal of Multidisciplinary Cancer Management (Electronic Version), 2019, 5 (1): 87- 97
[2]   左婷婷, 郑荣寿, 曾红梅 et al. 中国胃癌流行病学现状[J]. 中国肿瘤临床, 2017, 44 (1): 52- 58
ZUO Tingting , ZHENG Rongshou , ZENG Hongmei et al. Epidemiology of stomach cancer in China[J]. Chinese Journal of Clinical Oncology, 2017, 44 (1): 52- 58
doi: 10.3969/j.issn.1000-8179.2017.01.881
[3]   SIEGEL R , MA J , ZOU Z et al. Cancer statistics[J]. CA Cancer J Clin, 2014, 64 (1): 9- 29
doi: 10.3322/caac.21208
[4]   YAMASHITA S , KISHINO T , TAKAHASHI T et al. Genetic and epigenetic alterations in normal tissues have differential impacts on cancer risk among tissues[J]. Proc Natl Acad Sci U S A, 2018, 115 (6): 1328- 1333
doi: 10.1073/pnas.1717340115
[5]   PUNEE T , KAZMI H R , KUMARI S et al. Epigenetic mechanisms and events in gastric cancer-emerging novel biomarkers[J]. Pathol Oncol Res, 2018, 24 (4): 757- 770
doi: 10.1007/s12253-018-0410-z
[6]   BAYLIN S B , OHM J E . Epigenetic gene silencing in cancer-a mechanism for early oncogenic pathway addiction?[J]. Nat Rev Cancer, 2006, 6 (2): 107- 116
doi: 10.1038/nrc1799
[7]   PATEL T N , ROY S , RAVI R . Gastric cancer and related epigenetic alterations[J]. Ecancermedicalscience, 2017, 11:714
[8]   WEN J , ZHENG T , HU K et al. Promoter methylation of tumor-related genes as a potential biomarker using blood samples for gastric cancer detection[J]. Oncotarget, 2017, 8 (44): 77783- 77793
[9]   OOKI A , YAMASHITA K , YAMAGUCHI K et al. DNA damage-inducible gene, reprimo functions as a tumor suppressor and is suppressed by promoter methylation in gastric cancer[J]. Mol Cancer Res, 2013, 11 (11): 1362- 1374
doi: 10.1158/1541-7786.MCR-13-0091
[10]   BERNAL C , AGUAYO F , VILLARROEL C et al. Reprimo as a potential biomarker for early detection in gastric cancer[J]. Clin Cancer Res, 2008, 14 (19): 6264- 6269
doi: 10.1158/1078-0432.CCR-07-4522
[11]   Cancer Genome Atlas Research Network . Comprehensive molecular characterization of gastric adenocarcinoma[J]. Nature, 2014, 513 (7517): 202- 209
doi: 10.1038/nature13480
[12]   LING Z Q , TANAKA A , LI P et al. Microsatellite instability with promoter methylation and silencing of hMLH1 can regionally occur during progression of gastric carcinoma[J]. Cancer Lett, 2010, 297 (2): 244- 251
doi: 10.1016/j.canlet.2010.05.017
[13]   GRABSCH H I , TAN P . Gastric cancer pathology and underlying molecular mechanisms[J]. Dig Surg, 2013, 30 (2): 150- 158
doi: 10.1159/000350876
[14]   LEUNG W K , TO K F , CHU E S et al. Potential diagnostic and prognostic values of detecting promoter hypermethylation in the serum of patients with gastric cancer[J]. Br J Cancer, 2005, 92 (12): 2190- 2194
doi: 10.1038/sj.bjc.6602636
[15]   HU G , QIN L , ZHANG X et al. Epigenetic silencing of the MLH1 promoter in relation to the development of gastric cancer and its use as a biomarker for patients with microsatellite instability:a systematic analysis[J]. Cell Physiol Biochem, 2018, 45 (1): 148- 162
doi: 10.1159/000486354
[16]   LIU L , YANG X . Implication of reprimo and hMLH1 gene methylation in early diagnosis of gastric carcinoma[J]. Int J Clin Exp Pathol, 2015, 8 (11): 14977- 14982
[17]   LIN Z , LUO M , CHEN X et al. Combined detection of plasma ZIC1, HOXD10 and RUNX3 methylation is a promising strategy for early detection of gastric cancer and precancerous lesions[J]. J Cancer, 2017, 8 (6): 1038- 1044
doi: 10.7150/jca.18169
[18]   NI S , YE M , HUANG T . Short stature homeobox 2 methylation as a potential noninvasive biomarker in bronchial aspirates for lung cancer diagnosis[J]. Oncotarget, 2017, 8 (37): 61253- 61263
[19]   WIELSCHER M , VIERLINGER K , KEGLER U et al. Diagnostic performance of plasma DNA methylation profiles in lung cancer, pulmonary fibrosis and COPD[J]. EBioMedicine, 2015, 2 (8): 929- 936
doi: 10.1016/j.ebiom.2015.06.025
[20]   HU W , ZHENG W , LIU Q et al. Diagnostic accuracy of DNA methylation in detection of gastric cancer:a meta-analysis[J]. Oncotarget, 2017, 8 (68): 113142- 113152
[21]   MAEDA M , MORO H , USHIJIMA T . Mechanisms for the induction of gastric cancer by Helicobacter pylori infection:aberrant DNA methylation pathway[J]. Gastric Cancer, 2017, 20 (Suppl 1): 8- 15
[22]   YANG F , XUE X , ZHENG L et al. Long non-coding RNA GHET1 promotes gastric carcinoma cell proliferation by increasing c-Myc mRNA stability[J]. FEBS J, 2014, 281 (3): 802- 813
doi: 10.1111/febs.12625
[23]   ENDERLE D, SPIEL A, COTICCHIAC M, et al. Characterization of RNA from exosomes and other extracellular vesicles isolated by a novel spin column-based method[J/OL]. PLoS One, 2015, 10(8): e0136133.
[24]   LIU T , ZHANG X , GAO S et al. Exosomal long noncoding RNA CRNDE-h as a novel serum-based biomarker for diagnosis and prognosis of colorectal cancer[J]. Oncotarget, 2016, 7 (51): 85551- 85563
[25]   ZHAO R , ZHANG Y , ZHANG X et al. Exosomal long noncoding RNA HOTTIP as potential novel diagnostic and prognostic biomarker test for gastric cancer[J]. Mol Cancer, 2018, 17 (1): 68
doi: 10.1186/s12943-018-0817-x
[26]   FU M , HUANG Z , ZANG X et al. Long noncoding RNA LINC00978 promotes cancer growth and acts as a diagnostic biomarker in gastric cancer[J]. Cell Prolif, 2018, 51 (1):
[27]   ZHAO Y , GUO Q , CHEN J et al. Role of long non-coding rnahulc in cell proliferation, apoptosis and tumor metastasis of gastric cancer:a clinical and in vitro investigation[J]. Oncol Rep, 2014, 31 (1): 358- 364
doi: 10.3892/or.2013.2850
[28]   SHIN V Y , CHU K M . MiRNA as potential biomarkers and therapeutic targets for gastric cancer[J]. World J Gastroenterol, 2014, 20 (30): 10432- 10439
doi: 10.3748/wjg.v20.i30.10432
[29]   ZHANG Z , LI Z , GAO C et al. miR-21 plays a pivotal role in gastric cancer pathogenesis and progression[J]. Lab Invest, 2008, 88 (12): 1358- 1366
doi: 10.1038/labinvest.2008.94
[30]   WU J , LI G , WANG Z et al. Circulating microRNA-21 is a potential diagnostic biomarker in gastric cancer[J]. Dis Markers, 2015, 2015:435656
[31]   YANG R , FU Y , ZENG Y et al. Serum miR-20a is a promising biomarker for gastric cancer[J]. Biomed Rep, 2017, 6 (4): 429- 434
doi: 10.3892/br.2017.862
[32]   WANG N , WANG L , YANG Y et al. A serum exosomal microRNA panel as a potential biomarker test for gastric cancer[J]. Biochem Biophys Res Commun, 2017, 493 (3): 1322- 1328
doi: 10.1016/j.bbrc.2017.10.003
[33]   HANSEN T B , JENSEN T I , CLAUSEN B H et al. Natural RNA circles function as efficient microRNA sponges[J]. Nature, 2013, 495 (7441): 384- 388
doi: 10.1038/nature11993
[34]   MEMCZAK S, PAPAVASILEIOU P, PETERS O, et al. Identification and characterization of circular RNAs as a new class of putative biomarkers in human blood[J/OL]. PLoS One, 2015, 10(10): e0141214.
[35]   LI W H , SONG Y C , ZHANG H et al. Decreased expression of Hsa_circ_00001649 in gastric cancer and its clinical significance[J]. Dis Markers, 2017, 2017:4587698
[36]   HUANG M , HE Y R , LIANG L C et al. Circular RNA hsa_circ_0000745 may serve as a diagnostic marker for gastric cancer[J]. World J Gastroenterol, 2017, 23 (34): 6330- 6338
doi: 10.3748/wjg.v23.i34.6330
[37]   TONG Y , WU Y , SONG Z et al. The potential value of serum pepsinogen for the diagnosis of atrophic gastritis among the health check-up populations in China:a diagnostic clinical research[J]. BMC Gastroenterol, 2017, 17 (1): 88
doi: 10.1186/s12876-017-0641-6
[38]   KITAHARA F , KOBAYASHI K , SATO T et al. Accuracy of screening for gastric cancer using serum pepsinogen concentrations[J]. Gut, 1999, 44 (5): 693- 697
doi: 10.1136/gut.44.5.693
[39]   SUN L , TU H , LIU J et al. A comprehensive evaluation of fasting serum gastrin-17 as a predictor of diseased stomach in Chinese population[J]. Scand J Gastroenterol, 2014, 49 (10): 1164- 1172
doi: 10.3109/00365521.2014.950693
[40]   MIKI K . Gastric cancer screening by combined assay for serum anti-Helicobacter pylori IgG antibody and serum pepsinogen levels-"ABC method"[J]. Proc Jpn Acad Ser B Phys Biol Sci, 2011, 87 (7): 405- 414
doi: 10.2183/pjab.87.405
[41]   IKEDA F , SHIKATA K , HATA J et al. Combination of Helicobacter pylori antibody and serum pepsinogen as a good predictive tool of gastric cancer incidence:20-year prospective data from the hisayama study[J]. J Epidemiol, 2016, 26 (12): 629- 636
doi: 10.2188/jea.JE20150258
[42]   CHOI H S , LEE S Y , KIM J H et al. Combining the serum pepsinogen level and Helicobacter pylori antibody test for predicting the histology of gastric neoplasm[J]. J Dig Dis, 2014, 15 (6): 293- 298
doi: 10.1111/1751-2980.12144
[43]   YIN L K , SUN X Q , MOU D Z . Value of combined detection of serum CEA, CA72-4, CA19-9 and TSGF in the diagnosis of gastric cancer[J]. Asian Pac J Cancer Prev, 2015, 16 (9): 3867- 3870
doi: 10.7314/APJCP.2015.16.9.3867
[44]   KUCERA R , SMID D , TOPOLCAN O et al. Searching for new biomarkers and the use of multivariate analysis in gastric cancer diagnostics[J]. Anticancer Res, 2016, 36 (4): 1967- 1971
[45]   LIANG Y , WANG W , FANG C et al. Clinical significance and diagnostic value of serum CEA, CA19-9 and CA72-4 in patients with gastric cancer[J]. Oncotarget, 2016, 7 (31): 49565- 49573
[46]   GUNALDI M , GOKSU S , ERDEM D et al. Prognostic impact of platelet/lymphocyte and neutrophil/lymphocyte ratios in patients with gastric cancer:a multicenter study[J]. Int J Clin Exp Med, 2015, 8 (4): 5937- 5942
[47]   WU Y , JIANG M , QIN Y et al. Single and combined use of neutrophil-lymphocyte ratio, platelet-lymphocyte ratio and carcinoembryonic antigen in diagnosing gastric cancer[J]. Clin Chim Acta, 2018, 481:20- 24
doi: 10.1016/j.cca.2018.02.027
[48]   WU C Y , WU M S , CHIANG E P et al. Elevated plasma osteopontin associated with gastric cancer development, invasion and survival[J]. Gut, 2007, 56 (6): 782- 789
doi: 10.1136/gut.2006.109868
[49]   CHEN T, SUN L, HE C, et al. Serum OPN expression for identification of gastric cancer and atrophic gastritis and its influencing factors[J/OL]. PLoS One, 2014, 9(12): e114005.
[50]   ZENG Z , FU S , HU P et al. The diagnostic value of monoclonal gastric cancer 7 antigen:a systematic review with meta-analysis[J]. Clin Exp Med, 2014, 14 (3): 337- 343
doi: 10.1007/s10238-013-0246-5
[51]   ZHANG L , REN J , PAN K et al. Detection of gastric carcinoma-associated MG7-Ag by serum immuno-PCR assay in a high-risk Chinese population, with implication for screening[J]. Int J Cancer, 2010, 126 (2): 469- 473
doi: 10.1002/ijc.24739
[52]   SUN L , TU H , CHEN T et al. Three-dimensional combined biomarkers assay could improve diagnostic accuracy for gastric cancer[J]. Sci Rep, 2017, 7 (1): 11621
doi: 10.1038/s41598-017-12022-1
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