Skip to main content
Top
Published in: Esophagus 3/2019

01-07-2019 | Esophageal Cancer | Original Article

The effectiveness of serum midkine in detecting esophageal squamous cell carcinoma

Authors: Fumiaki Shiratori, Masaaki Ito, Satoshi Yajima, Takashi Suzuki, Yoko Oshima, Tatsuki Nanami, Kimihiko Funahashi, Hideaki Shimada

Published in: Esophagus | Issue 3/2019

Login to get access

Abstract

Background

Studies investigating serum midkine (s-MK) concentrations have employed a polyclonal antibody enzyme-linked immunosorbent assay system (ELISA), because the targeted polyclonal antibody has low specificity. We used a newly developed monoclonal antibody ELISA to investigate the prognostic and diagnostic capabilities of s-MK in patients with esophageal squamous cell carcinoma.

Methods

Serum samples from 102 patients with esophageal squamous cell carcinoma were analyzed using a newly developed monoclonal antibody ELISA specifically developed to detect s-MK. s-MK cutoff value was set at 421 pg/mL (mean + 2 SD) based on data from healthy controls. Clinicopathological characteristics, including tumor stage and positivity rates for two conventional tumor markers, serum p53 (s-p53-Abs) antibodies and SCC-antigen, were evaluated to assess a possible correlation with s-MK. The prognostic capability of a high s-MK level was evaluated using univariate and multivariate methods.

Results

Overall positive rate for s-MK concentrations: 21%. Large tumors (> 50 mm) showed significantly higher concentrations than smaller specimens, but other clinicopathological factors were not associated with s-MK. A combination assay using SCC-antigen together with s-p53-Abs and s-MK clearly increased our capability to detect esophageal squamous cell carcinoma. Although the difference was not statistically significant (P = 0.310), the high s-MK group experienced worse overall survival than our low s-MK group.

Conclusions

s-MK and conventional tumor marker combination increased our capability to detect esophageal squamous cell carcinoma. Although s-MK might be associated with esophageal squamous cell carcinoma progression, it was not an independent risk factor reducing patient survival. This study was registered as UMIN000014530.
Literature
2.
go back to reference Shimada H, Fukagawa T, Haga Y, et al. Does postoperative morbidity worsen the oncological outcome after radical surgery for gastrointestinal cancers? A systematic review of the literature. Ann Gastroenterol Surg. 2017;1:11–23.CrossRefPubMedPubMedCentral Shimada H, Fukagawa T, Haga Y, et al. Does postoperative morbidity worsen the oncological outcome after radical surgery for gastrointestinal cancers? A systematic review of the literature. Ann Gastroenterol Surg. 2017;1:11–23.CrossRefPubMedPubMedCentral
3.
go back to reference Saito F, Shimada H, Ogata H, et al. Detection of the early phase of esophageal cancer progression into lamina propria mucosae by the serum p53 antibody. Esophagus. 2017;14:366–9.CrossRef Saito F, Shimada H, Ogata H, et al. Detection of the early phase of esophageal cancer progression into lamina propria mucosae by the serum p53 antibody. Esophagus. 2017;14:366–9.CrossRef
4.
go back to reference Kadomatsu K, Tomomura M, Muramatsu T. cDNA cloning and sequencing of a new gene intensely expressed in early differentiation stages of embryonal carcinoma cells and in mid-gestation period of mouse embryogenesis. Biochem Biophys Res Commun. 1988;151:1312–8.CrossRefPubMed Kadomatsu K, Tomomura M, Muramatsu T. cDNA cloning and sequencing of a new gene intensely expressed in early differentiation stages of embryonal carcinoma cells and in mid-gestation period of mouse embryogenesis. Biochem Biophys Res Commun. 1988;151:1312–8.CrossRefPubMed
5.
go back to reference Kadomatsu K, Huang RP, Suganuma T, et al. A retinoic acid responsive gene MK found in the teratocarcinoma system is expressed in spatially and temporally controlled manner during mouse embryogenesis. J Cell Biol. 1990;10:607–16.CrossRef Kadomatsu K, Huang RP, Suganuma T, et al. A retinoic acid responsive gene MK found in the teratocarcinoma system is expressed in spatially and temporally controlled manner during mouse embryogenesis. J Cell Biol. 1990;10:607–16.CrossRef
6.
go back to reference Ibusuki M, Fujimori H, Yamamoto Y, et al. Midkine in plasma as a novel breast cancer marker. Cancer Sci. 2009;100:1735–9.CrossRefPubMed Ibusuki M, Fujimori H, Yamamoto Y, et al. Midkine in plasma as a novel breast cancer marker. Cancer Sci. 2009;100:1735–9.CrossRefPubMed
7.
go back to reference Rawnaq T, Dietrich L, Wolters-Eisfeld G, et al. The multifunctional growth factor midkine promotes proliferation and migration in pancreatic cancer. Mol Cancer Res. 2014;12:670–80.CrossRefPubMed Rawnaq T, Dietrich L, Wolters-Eisfeld G, et al. The multifunctional growth factor midkine promotes proliferation and migration in pancreatic cancer. Mol Cancer Res. 2014;12:670–80.CrossRefPubMed
8.
go back to reference Luo J, Wang X, Xia Z, et al. Transcriptional factor specificity protein 1 (SP1) promotes the proliferation of glioma cells by up-regulating midkine (MDK). Mol Biol Cell. 2015;26:430–9.CrossRefPubMedPubMedCentral Luo J, Wang X, Xia Z, et al. Transcriptional factor specificity protein 1 (SP1) promotes the proliferation of glioma cells by up-regulating midkine (MDK). Mol Biol Cell. 2015;26:430–9.CrossRefPubMedPubMedCentral
9.
10.
go back to reference Yamashita T, Shimada H, Tanaka S, et al. Serum midkine as a biomarker for malignancy, prognosis, and chemosensitivity in head and neck squamous cell carcinoma. Cancer Med. 2016;5:415–25.CrossRefPubMedPubMedCentral Yamashita T, Shimada H, Tanaka S, et al. Serum midkine as a biomarker for malignancy, prognosis, and chemosensitivity in head and neck squamous cell carcinoma. Cancer Med. 2016;5:415–25.CrossRefPubMedPubMedCentral
11.
go back to reference Shindo E, Nanki T, Kusunoki N, et al. The growth factor midkine may play a pathophysiological role in rheumatoid arthritis. Mod Rheumatol. 2017;27:54–9.CrossRefPubMed Shindo E, Nanki T, Kusunoki N, et al. The growth factor midkine may play a pathophysiological role in rheumatoid arthritis. Mod Rheumatol. 2017;27:54–9.CrossRefPubMed
12.
go back to reference Shimada H, Nabeya Y, Tagawa M, et al. Preoperative serum midkine concentration is a prognostic marker for esophageal squamous cell carcinoma. Cancer Sci. 2003;94:628–32.CrossRefPubMed Shimada H, Nabeya Y, Tagawa M, et al. Preoperative serum midkine concentration is a prognostic marker for esophageal squamous cell carcinoma. Cancer Sci. 2003;94:628–32.CrossRefPubMed
14.
go back to reference Dindo D, Demartines N, Clavien PA. Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg. 2004;240:205–13.CrossRefPubMedPubMedCentral Dindo D, Demartines N, Clavien PA. Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg. 2004;240:205–13.CrossRefPubMedPubMedCentral
16.
go back to reference Shimada H, Ochiai T, Nomura F. Japan p53 Antibody Research Group Titration of serum p53 antibodies in 1,085 patients with various types of malignant tumors: a multiinstitutional analysis by the Japan p53 Antibody Research Group. Cancer. 2003;97:682–9.CrossRefPubMed Shimada H, Ochiai T, Nomura F. Japan p53 Antibody Research Group Titration of serum p53 antibodies in 1,085 patients with various types of malignant tumors: a multiinstitutional analysis by the Japan p53 Antibody Research Group. Cancer. 2003;97:682–9.CrossRefPubMed
17.
go back to reference Shimada H, Nabeya Y, Okazumi S, et al. Prediction of survival with squamous cell carcinoma antigen in patients with resectable esophageal squamous cell carcinoma. Surgery. 2003;133:486–94.CrossRefPubMed Shimada H, Nabeya Y, Okazumi S, et al. Prediction of survival with squamous cell carcinoma antigen in patients with resectable esophageal squamous cell carcinoma. Surgery. 2003;133:486–94.CrossRefPubMed
Metadata
Title
The effectiveness of serum midkine in detecting esophageal squamous cell carcinoma
Authors
Fumiaki Shiratori
Masaaki Ito
Satoshi Yajima
Takashi Suzuki
Yoko Oshima
Tatsuki Nanami
Kimihiko Funahashi
Hideaki Shimada
Publication date
01-07-2019
Publisher
Springer Singapore
Published in
Esophagus / Issue 3/2019
Print ISSN: 1612-9059
Electronic ISSN: 1612-9067
DOI
https://doi.org/10.1007/s10388-019-00657-0

Other articles of this Issue 3/2019

Esophagus 3/2019 Go to the issue