Plasma Proteomics Analysis Identifying IGFBP2 as a Potential Diagnostic Biomarker for Laryngeal Squamous Cell Carcinoma

ABSTRACT Objective Currently, there are no blood biomarkers available for the early diagnosis of laryngeal squamous cell carcinoma (LSCC). The objective of this study was to search for potential plasma biomarkers for the diagnosis of LSCC. Methods Plasma samples were taken from patients with LSCC and healthy controls for proteomic analysis. An enzyme‐linked immunosorbent assay (ELISA) was employed to measure the expression levels of differentially expressed proteins in plasma. The expression of differential protein in LSCC cells was downregulated. Subsequently, the function of LSCC cells was evaluated using wound healing, transwell migration, incorporation of 5‐ethynyl‐2′‐deoxyuridine (EdU), and colony formation assays. Analysis of Plasma IGFBP2 Levels in Relation to Clinical Data and Evaluation of IGFBP2 as a Diagnostic and Prognostic Biomarker Using TCGA Database. Results A total of 16 differentially expressed proteins were identified in the plasma from patients with LSCC and healthy controls. Significant differences in protein expression patterns were observed between the LSCC patient group and the healthy control group. The expression of insulin‐like growth factor binding protein 2 (IGFBP2) in plasma of LSCC patients was significantly higher than that of healthy controls. After suppression of IGFBP2 expression, the migration, invasion, and proliferation abilities of LSCC cells were reduced and the expression of signal transduction and signal transducer and activator of transcription 3 (STAT3) was negatively regulated. The analysis of IGFBP2 expression in the TCGA‐LSCC data set showed a significant upregulation in tumor tissue compared to adjacent normal tissue. Furthermore, no significant differences in plasma IGFBP2 levels were observed with regard to gender, smoking status, history of malignancy, or tumor subsite. A positive correlation was observed between T stage and IGFBP2 levels. Kaplan–Meier survival analysis revealed that higher IGFBP2 expression levels were significantly associated with worse overall survival (OS) and progression‐free survival (PFS). Univariable Cox regression analysis identified high IGFBP2 expression as a significant predictor of poor prognosis (hazard ratio [HR] = 3.52, 95% confidence interval [CI]: 1.84–6.75, p < 0.001). Furthermore, multivariable Cox regression analysis confirmed the independent prognostic value of IGFBP2 expression, with a hazard ratio (HR) of 3.32 (95% CI: 1.63–6.78, p < 0.001). Conclusions IGFBP2 may play a role in the occurrence and development of LSCC as an oncogene and may be used as a potential plasma biomarker for the diagnosis of LSCC. IGFBP2 may be related to STAT3 in mechanism.