Serum midkine as a biomarker for malignancy, prognosis, and chemosensitivity in head and neck squamous cell carcinoma

Abstract

Improved therapies for individuals with head and neck squamous cell carcinoma (HNSCC) may be developed by identification of appropriate biomarkers. The aim of this study was to evaluate the usefulness of serum midkine measurement as a biomarker for HNSCC. Pretreatment serum midkine concentrations were measured in 103 patients with HNSCC and 116 control individuals by enzyme‐linked immunosorbent assay. Midkine expression in tumor tissues from 33 patients with HNSCC who underwent definitive surgical resection without preoperative treatment was examined by immunohistochemistry. The cut‐off serum midkine concentrations for predicting the presence of head and neck malignancy and chemosensitivity to induction chemotherapy, as determined using receiver operating characteristic curves, were 482 and 626 pg/mL, respectively. Spearman bivariate correlations showed positive correlations between serum midkine levels and immunohistochemistry staining score (r = 0.612, P < 0.001). The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of serum midkine concentration for detection of HNSCC were 57.3, 85.3, 77.6, 69.2, and 72.1%, respectively. However, for predicting the response to induction chemotherapy, the values were 84.6, 60.9, 71.0, 77.8, and 73.5%, respectively. Serum midkine concentration was identified as an independent prognostic factor by multivariate analysis, using Cox's proportional hazards model (P = 0.027). Overexpression of serum midkine yielded a relative risk of death of 3.77, with 95% confidence limits ranging from 1.15 to 17.0. Serum midkine levels in patients with HNSCC were associated with malignancy, chemosensitivity, and prognosis. Serum midkine may be a useful, minimally invasive biomarker for early detection, therapeutic decision‐making, and predicting prognosis.

Diagnostic impact of high serum midkine level in patients with gastric cancer

“…Similar to previous reports on mesothelioma and head and neck carcinoma, there was no clear association between tumor progression and s‐MK positive rate. Although the number of stage III/IV patients in our present study was not sufficient, we could not find significantly higher positive rates in stage III/IV patients than in stage I/II patients.…”

“…A commercially available enzyme‐linked immunosorbent assay kit for midkine (Cellmid, Sydney, NSW, Australia) was used to measure s‐MK levels . We determined s‐MK levels in the collected samples according to the manufacturer's protocol . Absorbance was measured with a microplate reader (Epoch 2; BioTek Instruments, Inc., Winooski, VT, USA) at a wavelength of 450 nm and was analyzed using Gen5 software (BioTek Instruments, Inc.).…”

“…Recently, an ELISA using monoclonal antibodies against midkine was developed . We evaluated the diagnostic abilities of this assay system using monoclonal antibodies for malignant mesothelioma and head and neck cancer . Only two reports used polyclonal antibody ELISA to evaluate s‐MK levels in patients with gastric cancer .…”

Review of emerging biomarkers in head and neck squamous cell carcinoma in the era of immunotherapy and targeted therapy

“…Blood is a relatively stable body fluid; several serum protein markers have traditionally been used to help predict outcomes in HNSCC patients, including CDK4, midkines, tumor necrosis factor (TNF)‐like weak inducer of apoptosis (TWEAK), IL‐2R, and VEGF‐A . However, some are not always cancer‐specific, giving rise to problems in distinguishing between malignant and inflammatory disease …”

Clinical value of jointly detection pleural fluid Midkine, pleural fluid adenosine deaminase, and pleural fluid carbohydrate antigen 125 in the identification of nonsmall cell lung cancer‐associated malignant pleural effusion

“…In recent years, it has been shown to be highly expressed in most cancers and play a central role in carcinogenesis, and is closely related to its aggressiveness . Thus, MK has become a new marker that is expected to be used in the diagnosis and prognosis of multiple cancers . X Xia’s study showed that MK in the serum and urine from NSCLC patients had a high expression, can be used to determine the prognosis…”