Megakaryocyte potentiating factor as a tumor marker of malignant pleural mesothelioma: Evaluation in comparison with mesothelin

Iwahori, Kota; Osaki, Tadashi; Serada, Satoshi; Fujimoto, Minoru; Suzuki, Hidekazu; Kishi, Yoshiro; Yokoyama, Akihito; Hamada, Hironobu; Fujii, Yoshihiro; Yamaguchi, Kentaro; Hirashima, Tomonori; Matsui, Kaoru; Tachibana, Isao; Nakamura, Yusuke; Kawase, Ichiro; Naka, Tetsuji

doi:10.1016/j.lungcan.2008.02.012

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Volume 62, Issue 1 , Pages 45-54, October 2008

Megakaryocyte potentiating factor as a tumor marker of malignant pleural mesothelioma: Evaluation in comparison with mesothelin

Kota Iwahori
- Department of Respiratory Medicine, Allergy, and Rheumatic Diseases, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Suita, Osaka 565-0871, Japan
- Laboratory for Immune Signal, National Institute of Biomedical Innovation, 7-6-8 Saito-Asagi, Ibaraki, Osaka 567-0085, Japan
Tadashi Osaki
- Department of Respiratory Medicine, Allergy, and Rheumatic Diseases, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Suita, Osaka 565-0871, Japan
- Corresponding author. Tel.: +81 6 6879 3833; fax: +81 6 6879 3839.
Satoshi Serada
- Laboratory for Immune Signal, National Institute of Biomedical Innovation, 7-6-8 Saito-Asagi, Ibaraki, Osaka 567-0085, Japan
Minoru Fujimoto
- Laboratory for Immune Signal, National Institute of Biomedical Innovation, 7-6-8 Saito-Asagi, Ibaraki, Osaka 567-0085, Japan
Hidekazu Suzuki
- Department of Thoracic Malignancy, Osaka Prefectural Medical Center for Respiratory and Allergic Diseases, 3-7-1 Habikino, Habikino, Osaka 583-8588, Japan
Yoshiro Kishi
- Department of Research and Development, Ina Institute, Medical & Biological Laboratories, Co., Ltd., 1063-103 Terasawaoka, Ina, Nagano 396-0002, Japan
Akihito Yokoyama
- Department of Hematology and Respiratory Medicine, Kochi University, 185-1, Okohchou-kohatu, Nanngoku, Kohchi 783-8505, Japan
Hironobu Hamada
- Department of Integrated Medicine and Informatics, Ehime University Graduate School of Medicine, Sizukawa, Ohonn, Ehime 791-0295, Japan
Yoshihiro Fujii
- Department of Research and Development, Ina Institute, Medical & Biological Laboratories, Co., Ltd., 1063-103 Terasawaoka, Ina, Nagano 396-0002, Japan
Kentaro Yamaguchi
- Department of Product Development, Ina Institute, Medical & Biological Laboratories, Co., Ltd., 1063-103 Terasawaoka, Ina, Nagano 396-0002, Japan
Tomonori Hirashima
- Department of Thoracic Malignancy, Osaka Prefectural Medical Center for Respiratory and Allergic Diseases, 3-7-1 Habikino, Habikino, Osaka 583-8588, Japan
Kaoru Matsui
- Department of Thoracic Malignancy, Osaka Prefectural Medical Center for Respiratory and Allergic Diseases, 3-7-1 Habikino, Habikino, Osaka 583-8588, Japan
Isao Tachibana
- Department of Respiratory Medicine, Allergy, and Rheumatic Diseases, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Suita, Osaka 565-0871, Japan
Yusuke Nakamura
- Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan
Ichiro Kawase
- Department of Respiratory Medicine, Allergy, and Rheumatic Diseases, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Suita, Osaka 565-0871, Japan
Tetsuji Naka
- Laboratory for Immune Signal, National Institute of Biomedical Innovation, 7-6-8 Saito-Asagi, Ibaraki, Osaka 567-0085, Japan

Received 30 October 2007; received in revised form 30 January 2008; accepted 14 February 2008. published online 04 April 2008.

Summary

Purpose

An early and reliable blood test is one deficiency in diagnosis of malignant pleural mesothelioma (MPM). Megakaryocyte potentiating factor (MPF) and mesothelin variants (MSLN), members of the mesothelin gene family, have been studied as candidate serum markers for MPM. We developed a novel enzyme-linked immunosorbent assay (ELISA) system to compare the diagnostic efficacy of MPF and MSLN in MPM and control groups.

Experimental design

MPF and MSLN were assayed with ELISA in 27 consecutive MPM patients and 129 controls including patients with lung cancer and asymptomatic asbestos-exposed subjects.

Results

Statistically significant elevation of serum MPF and MSLN levels was noted in MPM patients in comparison with every control group. The area under the receiver operating characteristic curve (AUC) was calculated for differentiation of MPM and lung cancer, healthy asbestos-exposed subjects, and healthy adults. While the AUC for serum MPF was 0.879, cut-off=19.1ng/ml (sensitivity=74.1%, specificity=90.4%), the AUC for serum MSLN was 0.713, cut-off=93.5ng/ml (sensitivity=59.3%, specificity=86.2%). Comparison between AUC for MPF and MSLN values shows that MPF is significantly superior to MSLN (p=0.025). Finally, there was a significant correlation between MPF and MSLN values for MPM (Pearson's correlation coefficient=0.77; p<0.001).

Conclusions

These findings suggest that diagnostic value of MPF for MPM was better than that of MSLN although both markers showed almost equal specificity for MPM.

Abbreviations: MPM, malignant pleural mesothelioma, MPF, megakaryocyte potentiating factor, MSLN, mesothelin variants 1 and 3, ELISA, enzyme-linked immunosorbent assay

Keywords: Mesothelioma, Megakaryocyte potentiating factor, Mesothelin, Tumor markers