Midkine is a potential novel marker for malignant mesothelioma with different prognostic and diagnostic values from mesothelin.
We evaluated possible diagnostic and prognostic values of serum midkine in malignant pleural mesothelioma in comparison with those of serum mesothelin, a well-established diagnostic biomarker.



Serum mesothelin and midkine levels were determined with an enzyme-linked immunosorbent assay. We examined specimens from 95 Turkish cases with malignant pleural mesothelioma, 56 metastatic cancers to pleura, 27 other types of benign pleural diseases and 20 benign asbestos pleurisy. The cut-off values were 1.5 nmol/L for mesothelin and 421 pg/mL for midkine.



Sensitivity and specificity of mesothelin were 51.6 and 71.4%, 51.6 and 85.2%, and 51.6 and 85% for differentiating mesothelioma from metastatic cancers to pleura, other benign pleural diseases and benign asbestos pleurisy, respectively. Sensitivity and specificity of midkine were 61.1 and 41.1%, 61.1 and 48.1%, and 61.1 and 75% to distinguish mesothelioma from metastatic cancers to pleura, other benign pleural diseases and benign asbestos pleurisy, respectively. Combination of both biomarkers did not improve the differential diagnostic efficacy. Mesothelin levels were elevated in the epitheloid type and in the advanced cases, but were not related to the prognosis. In contrast, elevated baseline levels of midkine were independently associated with a poor prognosis of mesothelioma patients after adjusting for the stage, the histological subtypes and treatment schedules (HR = 1.84; 95% CI: 1.09-3.09) (p = 0.022).



Serum mesothelin showed moderate sensitivity and high specificity to differentiate malignant pleural mesothelioma from metastatic malignancy to pleura and from benign pleural diseases. In contrast, midkine was a useful marker for predicting prognosis of mesothelioma patients.
Department of Chest Diseases, Medical Faculty, Lung and Pleural Cancers Research and Clinical Center, Eskisehir Osmangazi University, 26 000, Eskisehir, Turkey.
Guntulu
G
Ak
Department of Respirology, Graduate School of Medicine, Chiba University, Chiba, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan.
Yuji
Y
Tada
Department of Surgery, School of Medicine, Toho University, 6-11-1 Omorinishi, Ota-ku, Tokyo, 143-8541, Japan.
Hideaki
H
Shimada
Department of Public Health, Medical Faculty, Lung and Pleural Cancers Research and Clinical Center, Eskisehir Osmangazi University, 26 000, Eskisehir, Turkey.
Selma
S
Metintas
Department of Clinical Oncology, School of Medicine, Toho University, 6-11-1 Omorinishi, Ota-ku, Tokyo, 143-8541, Japan.
Masaaki
M
Ito
Department of Pathology, Tokyo Women's Medical University, Yachiyo Medical Center, Yachiyo, 477-96 Owadasinden, Yachiyo, 276-8524, Japan.
Kenzo
K
Hiroshima
Division of Pathology and Cell Therapy, Chiba Cancer Center Research Institute, 666-2 Nitona, Chuo-ku, Chiba, 260-8717, Japan. mtagawa@chiba-cc.jp.|Department of Molecular Biology and Oncology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan. mtagawa@chiba-cc.jp.
Masatoshi
M
Tagawa
Department of Chest Diseases, Medical Faculty, Lung and Pleural Cancers Research and Clinical Center, Eskisehir Osmangazi University, 26 000, Eskisehir, Turkey. muzaffermetintas@gmail.com.
Muzaffer
M
Metintas
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood*; D015331:Cohort Studies; D016207:Cytokines / Q000097:blood*; D005260:Female; D058851:GPI-Linked Proteins / Q000097:blood*; D006801:Humans; D008175:Lung Neoplasms / Q000097:blood* / Q000175:diagnosis / Q000453:epidemiology*; D008297:Male; D000090204:Mesothelin; D008654:Mesothelioma / Q000097:blood* / Q000175:diagnosis / Q000453:epidemiology*; D000086002:Mesothelioma, Malignant; D008875:Middle Aged; D000078792:Midkine; D011379:Prognosis; D012372:ROC Curve; D014421:Turkey / Q000453:epidemiology
D014408:Biomarkers, Tumor; D016207:Cytokines; D058851:GPI-Linked Proteins; D000078792:Midkine; D000090204:Mesothelin
Biomarker; Mesothelin; Mesothelioma; Midkine; Prognosis