CXCL10 serves as a potential serum biomarker complementing SCC-Ag for diagnosing cervical squamous cell carcinoma

Background Cervical squamous cell carcinoma (CESC) is the most common histological type of cervical cancer which is the major cause of death in women worldwide. Although squamous cell carcinoma antigen (SCC-Ag) is widely used to detect CESC, it is not sensitive and specific enough to predict the disease. Methods We investigated serum CXC motif chemokine 10 (CXCL10) as potential diagnostic biomarker in detecting CESC in this study. Serum levels of CXCL10 and SCC-Ag were measured by ELISA or automated immunoassay in 345 participants, including 189 patients with different stages of CESC, 75 patients with cervical intraepithelial neoplasia, and 81 healthy individuals. Performances of CXCL10 and SCC-Ag as single biomarkers were analyzed by the ROC curves. The changes of serum levels of CXCL10 and SCC-Ag in 10 longitudinal followed-up CESC patients with partial response (PR) during chemoradiotherapy or chemotherapy were evaluated. Results The two markers showed similar diagnostic capacity in distinguishing both CESC early stage from healthy controls (AUCCXCL10 = 0.740, AUCSCC-Ag = 0.710) and all CESC from healthy controls (AUCCXCL10 = 0.775, AUCSCC-Ag =0.793). Moreover, CXCL10 showed ability in distinguishing cervical intraepithelial neoplasia from healthy control (AUCCXCL10 = 0.727) and cervical cancer SCC-Ag-negative from healthy control. (AUCCXCL10 = 0.739). The combination of CXCL10 and SCC-Ag displayed significant improvement of AUCs than individual SCC-Ag or CXCL10 in the analysis groups (healthy vs all cervical cancer, healthy vs cervical cancer early stage). The AUCs were improved to 0.877 (AUCSCC-Ag = 0.793, P < 0.05) to distinguish healthy controls from all CESC and 0.828(AUCSCC-Ag = 0.710, P < 0.05) to distinguish healthy controls from CESC early stage by the combination of the two markers, respectively. Significant differences of serum CXCL10 levels were found between CESC patients at late tumor stage and CESC patients at early tumor stage (P < 0.01). Serum CXCL10 levels of the CESC patients who had partial response after treatment significantly decreased during treatment (P = 0.013), whose consistent and inconsistent frequency with the response were the same as serum SCC-Ag levels. Conclusions The results indicated that CXCL10 is a potential serum biomarker complementing SCC-Ag in prediction of CESC. CXCL10 showed ability in the diagnosis of SCC-Ag negative CESC and the combination of CXCL10 and SCC-Ag inhibited improved performance compared with SCC-Ag alone.

Automated summary

The study found that CXCL10 can serve as a serum biomarker for predicting cervical squamous cell carcinoma. CXCL10 showed good diagnostic ability in early detection, differentiating cervical intraepithelial neoplasia and SCC-Ag-negative cervical cancer, and the combination of CXCL10 and SCC-Ag improved the predictive performance.