Abstract
Serum tumor markers are blood-based biomarkers that are potentially useful in cancer detection, surveillance following curative surgery, prediction of drug response or resistance, and monitoring therapy in advance setting.
International guidelines do not accept tumor markers in the process of gastric cancer (GC) diagnosis. Their usefulness in GC can be mainly acknowledged in monitoring the effectiveness of antineoplastic therapy and the surveillance period and in identifying patients at risk for GC. The majority of the commonly used tumor biomarkers are neither specific nor sensitive; moreover, the issue of the almost complete lack of prospectively validated data remains.
The four most frequently used tumor biomarkers in GC follow-up are carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA 19-9), carbohydrate antigen 125 (CA 125), and carbohydrate antigen 72-4 (CA 72-4). In particular, the value of pretreatment serum CEA also represents an independent prognostic factor; CA 19-9 value is often used for the diagnosis of GC; CA 72-4 is considered the major marker for GC, mainly for detecting advanced stages; and elevated serum CA 125 levels are associated with a variety of benign and malignant causes of pelvic mass, including peritoneal metastasis of GC.
Specific gastric biomarkers, i.e., pepsinogen (PG) I, PGII, gastrin-17 (G-17), and anti-Helicobacter pylori (HP) antibodies, are being used to identify patients at risk for development of GC, particularly combined in a panel test (GastroPanel) which provides comprehensive information on both the structure and the function of the entire stomach mucosa.
In the era of precision medicine, liquid biopsy may represent a prognostic or predictive biomarker and a noninvasive tool for monitoring disease in terms of evaluation of response to systemic therapy as well as in monitoring clonal evolution. It could also be useful for screening and earlier detection, but patients with early stage disease often harbor a plasma concentration of mutant template molecules which is beyond the limit of detection of the most diffuse technologies.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Abbreviations
- AG:
-
Atrophic gastritis
- AUC:
-
Area under the curve
- CA 19-9:
-
Carbohydrate antigen 19-9
- CA 72-4:
-
Carbohydrate antigen 72-4
- CA 125:
-
Carbohydrate antigen 125
- CEA:
-
Carcinoembryonic antigen
- cfDNA:
-
Cell-free DNA
- CI:
-
Confidence interval
- CTCs:
-
Circulating tumor cells
- DSS:
-
Disease-specific survival
- DFS:
-
Disease-free survival
- G-17:
-
Gastrin-17
- GC:
-
Gastric cancer
- HP:
-
Helicobacter pylori
- HR:
-
Hazard ratio
- IgG:
-
Immunoglobulin G
- IM:
-
Intestinal metaplasia
- NCA:
-
Nonspecific cross-reacting antigen
- OR:
-
Odds ratio
- OS:
-
Overall survival
- PG:
-
Pepsinogen
- TAG-72:
-
Tumor-associated glycoprotein 72
References
McShane LM, et al. Reporting recommendations for tumor marker prognostic studies. J Clin Oncol. 2005;23:9067–72.
Sun Z, Zhang N. Clinical evaluation of CEA, CA19-9, CA72-4 and CA125 in gastric cancer patients with neoadjuvant chemotherapy. World J Surg Oncol. 2014;12:397.
Sturgeon CM, et al. National Academy of Clinical Biochemistry Laboratory Medicine Practice Guidelines for use of tumor markers in liver, bladder, cervical, and gastric cancers. Clin Chem. 2010;56:e1–48.
Smyth EC, et al. Gastric cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2016;27:v38–49.
SyrjäNen K. A panel of serum biomarkers (GastroPanel®) in non-invasive diagnosis of atrophic gastritis. Systematic review and meta-analysis. Anticancer Res. 2016;36:5133–44.
Zagari RM, et al. Systematic review with meta-analysis: diagnostic performance of the combination of pepsinogen, gastrin-17 and anti-Helicobacter pylori antibodies serum assays for the diagnosis of atrophic gastritis. Aliment Pharmacol Ther. 2017;46:657–67.
Gold P, Freedman SO. Specific carcinoembryonic antigens of the human digestive system. J Exp Med. 1965;122:467–81.
Benchimol S, et al. Carcinoembryonic antigen, a human tumor marker, functions as an intercellular adhesion molecule. Cell. 1989;57:327–34.
Hammarström S. The carcinoembryonic antigen (CEA) family: structures, suggested functions and expression in normal and malignant tissues. Semin Cancer Biol. 1999;9:67–81.
Öbrink B. CEA adhesion molecules: multifunctional proteins with signal-regulatory properties. Curr Opin Cell Biol. 1997;9:616–26.
Burtis CA, Ashwood ER, Bruns DE. Tietz textbook of clinical chemistry and molecular diagnostics – E-book. St. Louis: Elsevier Health Sciences; 2012.
Sell S. Serological cancer markers. New York: Springer Science & Business Media; 2012.
Cascinu S, Labianca R. La Medicina Oncologica: Diagnosi, Terapia e gestione clinica. Milano: Edra Masson; 2015.
Deng K, et al. The prognostic significance of pretreatment serum CEA levels in gastric cancer: a meta-analysis including 14651 patients. PLoS One. 2015;10(4):e0124151.
Shimada H, Noie T, Ohashi M, Oba K, Takahashi Y. Clinical significance of serum tumor markers for gastric cancer: a systematic review of literature by the Task Force of the Japanese Gastric Cancer Association. Gastric Cancer. 2014;17:26–33.
Takahashi Y, et al. The usefulness of CEA and/or CA19-9 in monitoring for recurrence in gastric cancer patients: a prospective clinical study. Gastric Cancer. 2003;6:142–5.
Wang T, et al. Carbohydrate antigen 19-9-positive gastric adenocarcinoma: autopsy findings and review of the literature. Case Rep Gastroenterol. 2017;11:545–53.
Koprowski H, et al. Colorectal carcinoma antigens detected by hybridoma antibodies. Somatic Cell Genet. 1979;5:957–71.
Hotakainen K, Tanner P, Alfthan H, Haglund C, Stenman U-H. Comparison of three immunoassays for CA 19-9. Clin Chim Acta. 2009;400:123–7.
Song Y, et al. Clinicopathologic and prognostic value of serum carbohydrate antigen 19-9 in gastric cancer: a meta-analysis. Dis Markers. 2015;2015:549843. https://doi.org/10.1155/2015/549843.
Fernandes LL, et al. CA72-4 antigen levels in serum and peritoneal washing in gastric cancer: correlation with morphological aspects of neoplasia. Arq Gastroenterol. 2007;44:235–9.
Căinap C, et al. Classic tumor markers in gastric cancer. Current standards and limitations. Clujul Med. 2015;88:111–5.
Emoto S, et al. Clinical significance of CA125 and CA72-4 in gastric cancer with peritoneal dissemination. Gastric Cancer. 2012;15:154–61.
Sharma S. Tumor markers in clinical practice: general principles and guidelines. Indian J Med Paediatr Oncol. 2009;30:1–8.
Chen X-Z, et al. Correlation between serum CA724 and gastric cancer: multiple analyses based on Chinese population. Mol Biol Rep. 2012;39:9031–9.
Abbas M, et al. The relevance of gastric cancer biomarkers in prognosis and pre- and post- chemotherapy in clinical practice. Biomed Pharmacother. 2017;95:1082–90.
Aloe S, et al. Prognostic value of serum and tumor tissue CA 72-4 content in gastric cancer. Int J Biol Markers. 2008;18:21–7.
Bast RC, et al. Reactivity of a monoclonal antibody with human ovarian carcinoma. J Clin Invest. 1981;68:1331–7.
Yin BWT, Lloyd KO. Molecular cloning of the CA125 ovarian cancer antigen: identification as a new mucin, MUC16. J Biol Chem. 2001;276:27371–5.
Sturgeon CM, et al. National Academy of Clinical Biochemistry Laboratory Medicine Practice Guidelines for use of tumor markers in testicular, prostate, colorectal, breast, and ovarian cancers. Clin Chem. 2008;54:e11–79.
Diamandis EP. Tumor markers: physiology, pathobiology, technology, and clinical applications. Washington, DC: American Association for Clinical Chemistry; 2002.
Kabawat SE, et al. Tissue distribution of a coelomic-epithelium-related antigen recognized by the monoclonal antibody OC125. Int J Gynecol Pathol. 1983;2:275–85.
Hwang GI, et al. Predictive value of preoperative serum CEA, CA19-9 and CA125 levels for peritoneal metastasis in patients with gastric carcinoma. Cancer Res Treat. 2004;36:178–81.
Nakata B, et al. Serum CA 125 level as a predictor of peritoneal dissemination in patients with gastric carcinoma. Cancer. 1998;83:2488–92.
Samloff IM. Immunologic studies of human group I pepsinogens. J Immunol. 1971;1950(106):962–8.
Nasrollahzadeh D, et al. Accuracy and cut-off values of pepsinogens I, II and gastrin 17 for diagnosis of gastric fundic atrophy: influence of gastritis. PLoS One. 2011;6:e26957.
Samloff IM, Varis K, Ihamaki T, Siurala M, Rotter JI. Relationships among serum pepsinogen I, serum pepsinogen II, and gastric mucosal histology. A study in relatives of patients with pernicious anemia. Gastroenterology. 1982;83:204–9.
Slpponen P, Kekki M, Haapakoski J, Ihamäki T, Siurala M. Gastric cancer risk in chronic atrophic gastritis: statistical calculations of cross-sectional data. Int J Cancer. 1985;35:173–7.
Dinis-Ribeiro M, et al. Meta-analysis on the validity of pepsinogen test for gastric carcinoma, dysplasia or chronic atrophic gastritis screening. J Med Screen. 2004;11:141–7.
Huang Y, et al. Significance of serum pepsinogens as a biomarker for gastric cancer and atrophic gastritis screening: a systematic review and meta-analysis. PLoS One. 2015;10:e0142080.
Miki K. Gastric cancer screening by combined assay for serum anti-Helicobacter pylori IgG antibody and serum pepsinogen levels – ‘ABC method’. Proc Jpn Acad Ser B Phys Biol Sci. 2011;87:405–14.
Lomba-Viana R, et al. Serum pepsinogen test for early detection of gastric cancer in a European Country. Eur J Gastroenterol Hepatol. 2012;24:37–41.
Farias CB, et al. Stimulation of proliferation of U138-MG glioblastoma cells by gastrin-releasing peptide in combination with agents that enhance cAMP signaling. Oncology. 2008;75:27–31.
Sawada M, Dickinson CJ. The G cell. Annu Rev Physiol. 1997;59:273–98.
Dockray GJ, Varro A, Dimaline R, Wang T. The gastrins: their production and biological activities. Annu Rev Physiol. 2001;63:119–39.
The EUROGAST Study Group. An international association between Helicobacter pylori infection and gastric cancer. Lancet. 1993;341:1359–63.
Yamada T. Helicobacter pylori in peptic ulcer disease. JAMA J Am Med Assoc. 1994;272:65.
Hallissey MT, Dunn JA, Fielding JW. Evaluation of pepsinogen A and gastrin-17 as markers of gastric cancer and high-risk pathologic conditions. Scand J Gastroenterol. 1994;29:1129–34.
Sun L, et al. A comprehensive evaluation of fasting serum gastrin-17 as a predictor of diseased stomach in Chinese population. Scand J Gastroenterol. 2014;49:1164–72.
Wang X, et al. The diagnostic value of gastrin-17 detection in atrophic gastritis: a meta-analysis. Medicine (Baltimore). 2016;95:e3599.
Correa P. Chronic gastritis: a clinico-pathological classification. Am J Gastroenterol. 1988;83:504–9.
Correa P. Human gastric carcinogenesis: a multistep and multifactorial process – First American Cancer Society Award Lecture on Cancer Epidemiology and Prevention. Cancer Res. 1992;52:6735–40.
de Vries AC, Haringsma J, Kuipers EJ. The detection surveillance and treatment of premalignant gastric lesions related to Helicobacter pylori infection. Helicobacter. 2007;12(1):1–15.
Agréus L, et al. Rationale in diagnosis and screening of atrophic gastritis with stomach-specific plasma biomarkers. Scand J Gastroenterol. 2012;47:136–47.
De Re V, et al. Pepsinogens to distinguish patients with gastric intestinal metaplasia and Helicobacter pylori infection among populations at risk for gastric cancer. Clin Transl Gastroenterol. 2016;7:e183.
Syrjänen KJ, Sipponen P, Härkönen M, Peetsalu A, Korpela S. Accuracy of the GastroPanel test in the detection of atrophic gastritis. Eur J Gastroenterol Hepatol. 2015;27:102–4.
Kurilovich S, et al. Stomach-specific Biomarkers (GastroPanel) can predict the development of gastric cancer in a Caucasian population: a longitudinal nested case-control study in Siberia. Anticancer Res. 2016;36:247–53.
Perakis S, Speicher MR. Emerging concepts in liquid biopsies. BMC Med. 2017;15(1):75.
Haber DA, Velculescu VE. Blood-based analyses of cancer: circulating tumor cells and circulating tumor DNA. Cancer Discov. 2014;4:650–61.
Bettegowda C, et al. Detection of circulating tumor DNA in early- and late-stage human malignancies. Sci Transl Med. 2014;6:224ra24.
Butler TM, Spellman PT, Gray J. Circulating-tumor DNA as an early detection and diagnostic tool. Curr Opin Genet Dev. 2017;42:14–21.
Nordgård O, Tjensvoll K, Gilje B, Søreide K. Circulating tumour cells and DNA as liquid biopsies in gastrointestinal cancer. Br J Surg. 2018;105:e110–20.
Bardelli A, Pantel K. Liquid Biopsies, What We Do Not Know (Yet). Cancer Cell. 2017;31:172–9.
Cohen JD, et al. Detection and localization of surgically resectable cancers with a multi-analyte blood test. Science. 2018;359(6378):926–30. https://doi.org/10.1126/science.aar3247.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2019 Springer Nature Switzerland AG
About this chapter
Cite this chapter
Steffan, A., Cervo, S., Fanotto, V., Puglisi, F. (2019). Serum Biomarkers in Gastric Cancer. In: Canzonieri, V., Giordano, A. (eds) Gastric Cancer In The Precision Medicine Era. Current Clinical Pathology. Humana, Cham. https://doi.org/10.1007/978-3-030-04861-7_6
Download citation
DOI: https://doi.org/10.1007/978-3-030-04861-7_6
Published:
Publisher Name: Humana, Cham
Print ISBN: 978-3-030-04860-0
Online ISBN: 978-3-030-04861-7
eBook Packages: MedicineMedicine (R0)