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Published in: Gastric Cancer 2/2020

01-03-2020 | Gastric Cancer | Original Article

Serum levels of ANOS1 serve as a diagnostic biomarker of gastric cancer: a prospective multicenter observational study

Authors: Mitsuro Kanda, Yun-Suhk Suh, Do Joong Park, Chie Tanaka, Sang-Hoon Ahn, Seong-Ho Kong, Hyuk-Joon Lee, Daisuke Kobayashi, Michitaka Fujiwara, Hideaki Shimada, BeLong Cho, Kenta Murotani, Hyung-Ho Kim, Han-Kwang Yang, Yasuhiro Kodera

Published in: Gastric Cancer | Issue 2/2020

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Abstract

Background

Development of high-performance serum biomarkers will likely improve treatment outcomes of patients with gastric cancer (GC). We previously identified the candidate serum markers, anosmin 1 (ANOS1), dihydropyrimidinase-like 3 (DPYSL3), and melanoma-associated antigen D2 (MAGE-D2) and evaluated their clinical significance through a single-center retrospective analysis. Here we conducted a prospective multicenter observational study aimed at validating the diagnostic performance of these potential markers.

Methods

We analyzed serum levels before and after surgery of the three potential biomarkers in patients with GC and healthy volunteers. Quantification of serum and GC tissue levels was performed using an ELISA.

Results

Area under the curve (AUC) values that discriminated patients with GC from healthy controls were − 0.7058, 0.6188, and 0.5031 for ANOS1, DPYSL3, and MAGED2, respectively. The sensitivity and specificity of the ANOS1 assay were 0.36 and 0.85, respectively. The AUC value of ANOS1 that discriminated patients with stage I GC from healthy controls was 0.7131. Serum ANOS1 levels were significantly elevated in patients with stage I GC compared with those of healthy controls (median 1179 ng/ml and 461 ng/ml, respectively, P < 0.0001) and decreased after resection of primary GC lesions (P < 0.0001). The combination of serum ANOS1 and DPYSL3 levels increased the AUC value that discriminated patients with GC from healthy controls. Serum levels of ANOS1 did not significantly correlate with those of carcinoembryonic antigen, carbohydrate antigen 19–9, or other markers of inflammation.

Conclusions

Serum levels of ANOS1 may serve as a useful diagnostic tool for managing GC.
Appendix
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Literature
1.
go back to reference Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68:394–424.CrossRef Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68:394–424.CrossRef
2.
go back to reference Van Cutsem E, Sagaert X, Topal B, Haustermans K, Prenen H. Gastric cancer. Lancet. 2016;388:2654–64.CrossRef Van Cutsem E, Sagaert X, Topal B, Haustermans K, Prenen H. Gastric cancer. Lancet. 2016;388:2654–64.CrossRef
3.
go back to reference Kanda M, Kodera Y. Recent advances in the molecular diagnostics of gastric cancer. World J Gastroenterol. 2015;21:9838–52.CrossRef Kanda M, Kodera Y. Recent advances in the molecular diagnostics of gastric cancer. World J Gastroenterol. 2015;21:9838–52.CrossRef
4.
go back to reference Ito M, Oshima Y, Yajima S, Suzuki T, Nanami T, Shiratori F, et al. Is high serum programmed death ligand 1 level a risk factor for poor survival in patients with gastric cancer? Ann Gastroenterol Surg. 2018;2:313–8.CrossRef Ito M, Oshima Y, Yajima S, Suzuki T, Nanami T, Shiratori F, et al. Is high serum programmed death ligand 1 level a risk factor for poor survival in patients with gastric cancer? Ann Gastroenterol Surg. 2018;2:313–8.CrossRef
5.
go back to reference Park DJ, Seo AN, Yoon C, Ku GY, Coit DG, Strong VE, et al. Serum VEGF-A and tumor vessel VEGFR-2 levels predict survival in Caucasian but not Asian patients undergoing resection for gastric adenocarcinoma. Ann Surg Oncol. 2015;22(Suppl 3):S1508–S15151515.CrossRef Park DJ, Seo AN, Yoon C, Ku GY, Coit DG, Strong VE, et al. Serum VEGF-A and tumor vessel VEGFR-2 levels predict survival in Caucasian but not Asian patients undergoing resection for gastric adenocarcinoma. Ann Surg Oncol. 2015;22(Suppl 3):S1508–S15151515.CrossRef
6.
go back to reference Kochi R, Yajima S, Nanami T, Suzuki T, Oshima Y, Tokura N, et al. Five-year postsurgical monitoring of serum p53 antibody for locally advanced esophageal squamous cell carcinoma. Clin J Gastroenterol. 2018;11:278–81.CrossRef Kochi R, Yajima S, Nanami T, Suzuki T, Oshima Y, Tokura N, et al. Five-year postsurgical monitoring of serum p53 antibody for locally advanced esophageal squamous cell carcinoma. Clin J Gastroenterol. 2018;11:278–81.CrossRef
7.
go back to reference He CZ, Zhang KH, Li Q, Liu XH, Hong Y, Lv NH. Combined use of AFP, CEA, CA125 and CAl9-9 improves the sensitivity for the diagnosis of gastric cancer. BMC Gastroenterol. 2013;13:87.CrossRef He CZ, Zhang KH, Li Q, Liu XH, Hong Y, Lv NH. Combined use of AFP, CEA, CA125 and CAl9-9 improves the sensitivity for the diagnosis of gastric cancer. BMC Gastroenterol. 2013;13:87.CrossRef
8.
go back to reference Leung WK, Wu MS, Kakugawa Y, Kim JJ, Yeoh KG, Goh KL, et al. Screening for gastric cancer in Asia: current evidence and practice. Lancet Oncol. 2008;9:279–87.CrossRef Leung WK, Wu MS, Kakugawa Y, Kim JJ, Yeoh KG, Goh KL, et al. Screening for gastric cancer in Asia: current evidence and practice. Lancet Oncol. 2008;9:279–87.CrossRef
9.
go back to reference Kanda M, Nomoto S, Oya H, Shimizu D, Takami H, Hibino S, et al. Dihydropyrimidinase-like 3 facilitates malignant behavior of gastric cancer. J Exp Clin Cancer Res. 2014;33:66.CrossRef Kanda M, Nomoto S, Oya H, Shimizu D, Takami H, Hibino S, et al. Dihydropyrimidinase-like 3 facilitates malignant behavior of gastric cancer. J Exp Clin Cancer Res. 2014;33:66.CrossRef
10.
go back to reference Kanda M, Nomoto S, Oya H, Takami H, Shimizu D, Hibino S, et al. The expression of melanoma-associated antigen D2 both in surgically resected and serum samples serves as clinically relevant biomarker of gastric cancer progression. Ann Surg Oncol. 2016;23(Suppl 2):214–21.CrossRef Kanda M, Nomoto S, Oya H, Takami H, Shimizu D, Hibino S, et al. The expression of melanoma-associated antigen D2 both in surgically resected and serum samples serves as clinically relevant biomarker of gastric cancer progression. Ann Surg Oncol. 2016;23(Suppl 2):214–21.CrossRef
11.
go back to reference Kanda M, Shimizu D, Fujii T, Sueoka S, Tanaka Y, Ezaka K, et al. Function and diagnostic value of Anosmin-1 in gastric cancer progression. Int J Cancer. 2016;138:721–30.CrossRef Kanda M, Shimizu D, Fujii T, Sueoka S, Tanaka Y, Ezaka K, et al. Function and diagnostic value of Anosmin-1 in gastric cancer progression. Int J Cancer. 2016;138:721–30.CrossRef
12.
go back to reference Zhang D, Zheng Y, Wang Z, Huang Q, Cao X, Wang F, et al. Comparison of the 7th and proposed 8th editions of the AJCC/UICC TNM staging system for esophageal squamous cell carcinoma underwent radical surgery. Eur J Surg Oncol. 2017;43:1949–55.CrossRef Zhang D, Zheng Y, Wang Z, Huang Q, Cao X, Wang F, et al. Comparison of the 7th and proposed 8th editions of the AJCC/UICC TNM staging system for esophageal squamous cell carcinoma underwent radical surgery. Eur J Surg Oncol. 2017;43:1949–55.CrossRef
13.
go back to reference Szasz AM, Lanczky A, Nagy A, Forster S, Hark K, Green JE, et al. Cross-validation of survival associated biomarkers in gastric cancer using transcriptomic data of 1065 patients. Oncotarget. 2016;7:49322–33.CrossRef Szasz AM, Lanczky A, Nagy A, Forster S, Hark K, Green JE, et al. Cross-validation of survival associated biomarkers in gastric cancer using transcriptomic data of 1065 patients. Oncotarget. 2016;7:49322–33.CrossRef
14.
go back to reference Aikou S, Ohmoto Y, Gunji T, Matsuhashi N, Ohtsu H, Miura H, et al. Tests for serum levels of trefoil factor family proteins can improve gastric cancer screening. Gastroenterology. 2011;141:837–45.e1-7.CrossRef Aikou S, Ohmoto Y, Gunji T, Matsuhashi N, Ohtsu H, Miura H, et al. Tests for serum levels of trefoil factor family proteins can improve gastric cancer screening. Gastroenterology. 2011;141:837–45.e1-7.CrossRef
15.
go back to reference Katai H, Ishikawa T, Akazawa K, Isobe Y, Miyashiro I, Oda I, et al. Five-year survival analysis of surgically resected gastric cancer cases in Japan: a retrospective analysis of more than 100,000 patients from the nationwide registry of the Japanese Gastric Cancer Association (2001–2007). Gastric Cancer. 2018;21:144–54.CrossRef Katai H, Ishikawa T, Akazawa K, Isobe Y, Miyashiro I, Oda I, et al. Five-year survival analysis of surgically resected gastric cancer cases in Japan: a retrospective analysis of more than 100,000 patients from the nationwide registry of the Japanese Gastric Cancer Association (2001–2007). Gastric Cancer. 2018;21:144–54.CrossRef
16.
go back to reference Ahn HS, Shin YS, Park PJ, Kang KN, Kim Y, Lee HJ, et al. Serum biomarker panels for the diagnosis of gastric adenocarcinoma. Br J Cancer. 2012;106:733–9.CrossRef Ahn HS, Shin YS, Park PJ, Kang KN, Kim Y, Lee HJ, et al. Serum biomarker panels for the diagnosis of gastric adenocarcinoma. Br J Cancer. 2012;106:733–9.CrossRef
17.
go back to reference Shimada H. p53 molecular approach to diagnosis and treatment of esophageal squamous cell carcinoma. Ann Gastroenterol Surg. 2018;2:266–73.CrossRef Shimada H. p53 molecular approach to diagnosis and treatment of esophageal squamous cell carcinoma. Ann Gastroenterol Surg. 2018;2:266–73.CrossRef
18.
go back to reference Duraes C, Almeida GM, Seruca R, Oliveira C, Carneiro F. Biomarkers for gastric cancer: prognostic, predictive or targets of therapy? Virchows Arch. 2014;464:367–78.CrossRef Duraes C, Almeida GM, Seruca R, Oliveira C, Carneiro F. Biomarkers for gastric cancer: prognostic, predictive or targets of therapy? Virchows Arch. 2014;464:367–78.CrossRef
19.
go back to reference Murcia-Belmonte V, Esteban PF, Garcia-Gonzalez D, De Castro F. Biochemical dissection of Anosmin-1 interaction with FGFR1 and components of the extracellular matrix. J Neurochem. 2010;115:1256–65.CrossRef Murcia-Belmonte V, Esteban PF, Garcia-Gonzalez D, De Castro F. Biochemical dissection of Anosmin-1 interaction with FGFR1 and components of the extracellular matrix. J Neurochem. 2010;115:1256–65.CrossRef
20.
go back to reference Choy CT, Kim H, Lee JY, Williams DM, Palethorpe D, Fellows G, et al. Anosmin-1 contributes to brain tumor malignancy through integrin signal pathways. Endocr Relat Cancer. 2014;21:85–99.CrossRef Choy CT, Kim H, Lee JY, Williams DM, Palethorpe D, Fellows G, et al. Anosmin-1 contributes to brain tumor malignancy through integrin signal pathways. Endocr Relat Cancer. 2014;21:85–99.CrossRef
21.
go back to reference de Castro F, Seal R, Maggi R. ANOS1: a unified nomenclature for Kallmann syndrome 1 gene (KAL1) and anosmin-1. Brief Funct Genomics. 2017;16:205–10.CrossRef de Castro F, Seal R, Maggi R. ANOS1: a unified nomenclature for Kallmann syndrome 1 gene (KAL1) and anosmin-1. Brief Funct Genomics. 2017;16:205–10.CrossRef
22.
go back to reference Murcia-Belmonte V, Esteban PF, Martinez-Hernandez J, Gruart A, Lujan R, Delgado-Garcia JM, et al. Anosmin-1 over-expression regulates oligodendrocyte precursor cell proliferation, migration and myelin sheath thickness. Brain Struct Funct. 2016;221:1365–85.CrossRef Murcia-Belmonte V, Esteban PF, Martinez-Hernandez J, Gruart A, Lujan R, Delgado-Garcia JM, et al. Anosmin-1 over-expression regulates oligodendrocyte precursor cell proliferation, migration and myelin sheath thickness. Brain Struct Funct. 2016;221:1365–85.CrossRef
23.
go back to reference Qi L, Zhang W, Cheng Z, Tang N, Ding Y. Study on molecular mechanism of ANOS1 promoting development of colorectal cancer. PLoS ONE. 2017;12:e0182964.CrossRef Qi L, Zhang W, Cheng Z, Tang N, Ding Y. Study on molecular mechanism of ANOS1 promoting development of colorectal cancer. PLoS ONE. 2017;12:e0182964.CrossRef
24.
go back to reference Rosslenbroich V, Dai L, Baader SL, Noegel AA, Gieselmann V, Kappler J. Collapsin response mediator protein-4 regulates F-actin bundling. Exp Cell Res. 2005;310:434–44.CrossRef Rosslenbroich V, Dai L, Baader SL, Noegel AA, Gieselmann V, Kappler J. Collapsin response mediator protein-4 regulates F-actin bundling. Exp Cell Res. 2005;310:434–44.CrossRef
25.
go back to reference Chomez P, De Backer O, Bertrand M, De Plaen E, Boon T, Lucas S. An overview of the MAGE gene family with the identification of all human members of the family. Cancer Res. 2001;61:5544–51.PubMed Chomez P, De Backer O, Bertrand M, De Plaen E, Boon T, Lucas S. An overview of the MAGE gene family with the identification of all human members of the family. Cancer Res. 2001;61:5544–51.PubMed
26.
go back to reference Xiao J, Chen HS. Biological functions of melanoma-associated antigens. World J Gastroenterol. 2004;10:1849–53.CrossRef Xiao J, Chen HS. Biological functions of melanoma-associated antigens. World J Gastroenterol. 2004;10:1849–53.CrossRef
27.
go back to reference Papageorgio C, Brachmann R, Zeng J, Culverhouse R, Zhang W, McLeod H. MAGED2: a novel p53-dissociator. Int J Oncol. 2007;31:1205–11.PubMed Papageorgio C, Brachmann R, Zeng J, Culverhouse R, Zhang W, McLeod H. MAGED2: a novel p53-dissociator. Int J Oncol. 2007;31:1205–11.PubMed
28.
go back to reference Feng F, Tian Y, Xu G, Liu Z, Liu S, Zheng G, et al. Diagnostic and prognostic value of CEA, CA19-9, AFP and CA125 for early gastric cancer. BMC Cancer. 2017;17:737.CrossRef Feng F, Tian Y, Xu G, Liu Z, Liu S, Zheng G, et al. Diagnostic and prognostic value of CEA, CA19-9, AFP and CA125 for early gastric cancer. BMC Cancer. 2017;17:737.CrossRef
29.
go back to reference Uda H, Kanda M, Tanaka C, Kobayashi D, Inaoka K, Tanaka Y, et al. Perioperative serum carcinoembryonic antigen levels predict recurrence and survival of patients with pathological T2–4 gastric cancer treated with curative gastrectomy. Dig Surg. 2018;35:55–63.CrossRef Uda H, Kanda M, Tanaka C, Kobayashi D, Inaoka K, Tanaka Y, et al. Perioperative serum carcinoembryonic antigen levels predict recurrence and survival of patients with pathological T2–4 gastric cancer treated with curative gastrectomy. Dig Surg. 2018;35:55–63.CrossRef
30.
go back to reference Yanagawa T, Hayashi Y, Nishida T, Yoshida H, Yura Y, Azuma M, et al. Immunohistochemical demonstration of carcinoembryonic antigen (CEA) on tissue sections from squamous cell head and neck cancer and plasma CEA levels of the patients. Int J Oral Maxillofac Surg. 1986;15:296–306.CrossRef Yanagawa T, Hayashi Y, Nishida T, Yoshida H, Yura Y, Azuma M, et al. Immunohistochemical demonstration of carcinoembryonic antigen (CEA) on tissue sections from squamous cell head and neck cancer and plasma CEA levels of the patients. Int J Oral Maxillofac Surg. 1986;15:296–306.CrossRef
31.
go back to reference Maehara Y, Sugimachi K, Akagi M, Kakegawa T, Shimazu H, Tomita M. Serum carcinoembryonic antigen level increases correlate with tumor progression in patients with differentiated gastric carcinoma following noncurative resection. Cancer Res. 1990;50:3952–5.PubMed Maehara Y, Sugimachi K, Akagi M, Kakegawa T, Shimazu H, Tomita M. Serum carcinoembryonic antigen level increases correlate with tumor progression in patients with differentiated gastric carcinoma following noncurative resection. Cancer Res. 1990;50:3952–5.PubMed
32.
go back to reference Li M, Li JY, Zhao AL, He JS, Zhou LX, Li YA, et al. Comparison of carcinoembryonic antigen prognostic value in serum and tumour tissue of patients with colorectal cancer. Colorectal Dis. 2009;11:276–81.CrossRef Li M, Li JY, Zhao AL, He JS, Zhou LX, Li YA, et al. Comparison of carcinoembryonic antigen prognostic value in serum and tumour tissue of patients with colorectal cancer. Colorectal Dis. 2009;11:276–81.CrossRef
Metadata
Title
Serum levels of ANOS1 serve as a diagnostic biomarker of gastric cancer: a prospective multicenter observational study
Authors
Mitsuro Kanda
Yun-Suhk Suh
Do Joong Park
Chie Tanaka
Sang-Hoon Ahn
Seong-Ho Kong
Hyuk-Joon Lee
Daisuke Kobayashi
Michitaka Fujiwara
Hideaki Shimada
BeLong Cho
Kenta Murotani
Hyung-Ho Kim
Han-Kwang Yang
Yasuhiro Kodera
Publication date
01-03-2020
Publisher
Springer Singapore
Published in
Gastric Cancer / Issue 2/2020
Print ISSN: 1436-3291
Electronic ISSN: 1436-3305
DOI
https://doi.org/10.1007/s10120-019-00995-z

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