Midkine is a potential novel marker for malignant mesothelioma with different prognostic and diagnostic values from mesothelin

Our plain-English summary of Midkine is a potential novel marker for malignant mesothelioma with different prognostic and diagnostic values from mesothelin, by G. Ak, Y. Tada, H. Shimada, et al (BMC Cancer, 2017).

The study

• Authors: G. Ak, Y. Tada, H. Shimada, S. Metintas, M. Ito, K. Hiroshima, M. Tagawa, M. Metintas
• Journal: BMC Cancer
• Published: 2017;17(1):212
• Cited by: 18 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: 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.

Methods: 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.

Results: 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).

Conclusions: 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.

In plain English

The authors measured the blood markers mesothelin and midkine in stored serum from 198 patients at Eskisehir Osmangazi University Hospital, Turkey. Of these, 95 had malignant pleural mesothelioma, 56 had cancers spread to the pleura from elsewhere, 20 had benign asbestos pleurisy and 27 had other benign pleural diseases. Most patients came from an area of Turkey with environmental asbestos exposure. Mesothelin separated mesothelioma from the other diseases. At its cut-off it identified 51.6% of mesothelioma cases, with specificity from 71.4% to 85.2% across comparison groups. Midkine identified 61.1% of cases, but its specificity was lower, from 41.1% to 75% across comparison groups. Combining the markers did not improve diagnosis. Neither marker separated early-stage mesothelioma from benign asbestos pleurisy. In mesothelioma patients, mesothelin was not related to prognosis. High midkine was independently associated with poorer survival (hazard ratio 1.84; 95% CI 1.09-3.09). Median survival was 13.7 months (95% CI 11.33-16.13) below the midkine cut-off and 8.4 months (95% CI 6.50-10.36) above it. The authors concluded that midkine is a novel biomarker with a different clinical value from mesothelin.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Diagnostic and prognostic biomarker study comparing patient groups, using serum samples from a hospital tissue bank
• Who was studied: 198 patients diagnosed and treated at Eskisehir Osmangazi University Hospital, Turkey: 95 with malignant pleural mesothelioma, 56 with metastatic cancers to the pleura, 20 with benign asbestos pleurisy and 27 with other benign pleural diseases. Study dates are not given.
• Exposure: The study measured serum mesothelin (cut-off 1.5 nmol/L) and serum midkine (cut-off 421 pg/mL). Asbestos exposure was not measured. Most patients came from an area of Turkey with environmental asbestos exposure, and no fiber type is named.
• Main results:
  • Mesothelin differentiated mesothelioma from non-mesothelioma diseases. Midkine was of limited value, discriminating mesothelioma only from benign asbestos pleurisy.
  • Mesothelin had a sensitivity of 51.6% in every comparison. Its specificity was 71.4% versus metastatic cancers to the pleura, 85.2% versus other benign pleural diseases and 85% versus benign asbestos pleurisy.
  • Midkine had a sensitivity of 61.1% in every comparison. Its specificity was 41.1% versus metastatic cancers to the pleura, 48.1% versus other benign pleural diseases and 75% versus benign asbestos pleurisy.
  • Combining the two markers did not improve diagnostic accuracy.
  • Neither marker distinguished early-stage (stage I to II) mesothelioma from benign asbestos pleurisy. Mesothelin had an AUC of 0.655, sensitivity 42.9% and specificity 85%; midkine had an AUC of 0.557, sensitivity 33.3% and specificity 95.0%.
  • In mesothelioma patients, mesothelin levels were higher in the epitheloid type and in advanced cases, but were not related to prognosis.
  • Baseline levels of neither marker were associated with response to chemotherapy. Response was evaluated in 45 of 51 patients given cisplatin plus pemetrexed-based treatment.
  • In mesothelioma patients, high serum midkine was independently associated with poor prognosis after adjustment for stage, histological subtype and treatment (HR = 1.84; 95% CI 1.09-3.09; p = 0.022).
  • Median survival was 13.7 months (95% CI 11.33-16.13) for mesothelioma patients with midkine below 421 pg/ml, and 8.4 months (95% CI 6.50-10.36) for those above (log-rank p = 0.003).
• The authors' conclusion: The authors concluded that mesothelin is a useful diagnostic marker with moderate sensitivity and relatively high specificity but is not associated with prognosis. They concluded that midkine differentiates mesothelioma only from benign asbestos pleurisy, but its baseline level predicted prognosis, making it a novel biomarker with a different clinical value from mesothelin.
• Limitations the authors state:
  • The authors said the chemotherapy-response findings need careful evaluation, because sensitivity to chemotherapy differed among histological types and stages. They said this should be examined prospectively over time.
  • The authors had not analyzed midkine levels in the tumor specimens themselves.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer, Mesothelioma.

Medical terms in this study, explained in our Lexicon: Malignant Mesothelioma, Mesothelin, Pleural Mesothelioma, Biomarker, Pleura, Pleurisy, Mesothelioma, Prognosis.

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