Expression of CLIC1 as a potential biomarker for oral squamous cell carcinoma: a preliminary study

Abstract

PurposeCLIC1, a member of the highly conserved class ion-channel protein family, is frequently upregulated in multiple human malignancies and has been demonstrated to play a critical role in cell proliferation, apoptosis, and invasion. However, limited is known about its expression, biological functions, and action mechanism in oral malignancies. We aimed to evaluate whether CLIC1 could be a biomarker for oral squamous cell carcinoma (OSCC).MethodsImmunohistochemistry was used to analyze the expression of CLIC1 in tissue. CLIC1 protein and mRNA were measured through Western immunoblotting and quantitative real-time PCR. CLIC1 protein expression in plasma was detected via ELISA. A total of 72 OSCC specimens were recruited in this study for evaluation of correlations of CLIC1 with clinicopathological features and survival.ResultsCLIC1 was significantly overexpressed in tissue and plasma of OSCC patients. It was found that upregulated CLIC1 was distinctly correlated with histological grade, TNM stage, and tumor size. Meanwhile, Kaplan–Meier survival analysis showed that OSCC patients with high CLIC1 expression had remarkably poorer overall survival rate than those with low CLIC1 expression. Multivariate Cox regression analysis revealed that CLIC1 was the independent prognostic factor for overall survival rate of OSCC patients. In addition, Pearson correlation analysis showed that CLIC1 was associated with multiple tumor-associated genes.ConclusionThese results indicated that CLIC1 acts as a molecular target in OSCC and may present a novel diagnostic marker and therapeutic target for OSCC.

Intracellular Chloride Ion Channel Protein-1 Expression in Clear Cell Renal Cell Carcinoma

“…Recently, indeed, Thuringer et al have reported this very crosstalk between glioblastoma cells and endothelial cells that is mediated by CLIC1 released through extracellular vesicles by tumor cells and captured by endothelial cells, which are induced to sprout and form tubes in 3D matrices (34). CLIC1 has already been reported as a potential biomarker for some malignant tumors (6,10,16) and a potential therapeutic target for new treatments in cancer. Its expression in both tumor and endothelial cells may pave the way for the development of future anti-CLIC1 therapy, able to target both tumor and its associated vessels.…”

“…Amongst the six members of intracellular chloride ion channel protein family (CLICs), CLIC1 and CLIC4 have been extensively studied regarding their involvement in tumor development (4). Indeed, CLIC1 is overexpressed in several tumor types, such as gastric cancer (5), oral squamous cell carcinomas (6) or glioblastoma (7). Recently, Barbieri et al reported that CLIC1 inhibition induces glioblastoma growth inhibition, mainly by acting on CLIC1-rich glioblastoma stem cells, decreasing their proliferation and subsequently tumor progression (8).…”

Chloride Intracellular Channel 1 is a Potential Biomarker for Breast Cancer

“… 24 Xu et al detected highly expressed CLIC1 protein in the blood of patients with oral squamous cell carcinoma. After the patients were treated with surgery and chemotherapy, the expression level of CLIC1 protein was significantly reduced, 25 which suggested that CLIC1 may become a tumor therapeutic target and a biomarker for judging the therapeutic effect. In addition, CLIC1 significantly affected the prognosis of ovarian cancer patients.…”

Characterization of Cancer Stem Cell Characteristics and Development of a Prognostic Stemness Index Cell-Related Signature in Oral Squamous Cell Carcinoma

“…TNM represents an effective clinical tool for predicting OSCC prognoses [25]. Moreover, molecular biomarkers could become a beneficial supplement to TNM for improving the predictive accuracy [26]. Also, these molecules exert key functions on OSCC progression as well as serve as novel therapeutic targets [27].…”