Combined Detection of ACTN4 and SCC-Ag is a Promising Serological Biomarker for Cervical Intraepithelial Neoplasia 3 or Worse: A Case–Control Study

PURPOSE: Cervical cancer (CC) is a common malignancy in women. Squamous cell carcinoma antigen (SCC-Ag) and cancer antigen (CA)-125 are widely used to help diagnose CC, but novel tumour markers with superior sensitivity and specificity are needed. α-Actinin 4(ACTN4) is overexpressed in CC, though its diagnostic value for CC is unclear. This study examined the diagnostic value of ACTN4 and SCC-Ag as biomarkers for cervical intraepithelial neoplasia (CIN) 3 or worse. METHODS: Women screened for CC at Fujian Medical University Union Hospital were recruited from 2017.1 to 2018.5. Cervical tissues and blood were collected at the same time. Patients pathologically diagnosed as CIN3+ or NILM/CIN1/CIN2 were classified into the case and control groups, respectively. ACTN4 mRNA and protein levels were detected through quantitative PCR and immunohistochemistry, respectively, and ACTN4 and SCC-Ag concentrations were analysed by ELISA. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), positive likelihood rate (PLR), negative likelihood rate (NLR), and Youden index (YI) of ACTN4 and SCC-Ag were evaluated. The optimum cut-off points for ACTN4 and SCC-Ag were determined by receiver operating characteristic (ROC) curve analysis, and accuracy was evaluated by the area under the ROC curve. RESULTS: In total, 105 patients were classified as CIN3+ cases and 106 as controls. The median ACTN4 levels in case and control tissues were 10.6 and 4.15, respectively. The ACTN4 and SCC-Ag concentrations were significantly higher in cases than controls (P(ACTN4)=0.0007; P(SCC-Ag)=0.0067). The sensitivity, specificity, PPV, NPV, PLR, NLR and YI of ACTN4 were 68.6%, 76.3%, 76.3%, 72.5%, 2.89, 0.41 and 44.9, respectively; SCC-Ag had a similar diagnostic value (P>0.05), and ACTN4 combined with SCC-Ag had a superior diagnostic value (75.6%, 87.5%, 88.6%, 73.7%, 6.05, 0.28, and 63.1, respectively). CONCLUSION: Combined ACTN4 and SCC-Ag detection is a promising serological biomarker for patients with CIN3 or worse.