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.
Highlights
Head and neck squamous cell carcinoma (HNSCC) is the seventh most frequent cancer in the world, with over 680,000 patients diagnosed annually [1]
Recent studies have reported the early detection of head and neck cancers owing to the progression of diagnostic technologies, such as positron-emission tomography (PET), high-resolution electronic endoscopy, and optical imaging technologies [3,4,5,6]
There are no criteria published by the American Joint Committee on Cancer (AJCC) regarding stage classification for external auditory canal (EAC; n = 2) and occult primary (OP; n = 4) cases, we defined their stages in this study, using the Pittsburgh classification [28] for T classification of EAC cases and the Seventh International Union Against Cancer (UICC) TNM staging system of oropharyngeal or hypopharyngeal cancer for N and M classifications for OP cases
Summary
Head and neck squamous cell carcinoma (HNSCC) is the seventh most frequent cancer in the world, with over 680,000 patients diagnosed annually [1]. Recent studies have reported the early detection of head and neck cancers owing to the progression of diagnostic technologies, such as positron-emission tomography (PET), high-resolution electronic endoscopy, and optical imaging technologies (e.g., narrow band imaging [NBI] and i-scan) [3,4,5,6]. Detection is the key to improved prognosis in patients with HNSCC. Early detection of HNSCC provides considerable benefits to patients, including improved prognoses and functional preservation in deglutition, phonation, and articulation by transoral resection of local tumors. Some molecules have been reported as serum tumor markers for HNSCC, the sensitivity of these molecules for early detection of HNSCC is insufficient. The development of more sensitive tumor markers for the detection of early stage HNSCC would improve cancer screening and posttreatment follow up
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