Serum Anti-PDLIM1 Autoantibody as Diagnostic Marker in Ovarian Cancer

Abstract

BackgroundSerum autoantibodies (AAbs) against tumor-associated antigens (TAAs) could be useful biomarkers for cancer detection. This study aims to evaluate the diagnostic value of autoantibody against PDLIM1 for improving the detection of ovarian cancer (OC).MethodsImmunohistochemistry (IHC) test in tissue array containing 280 OC tissues, 20 adjacent tissues, and 8 normal ovarian tissues was performed to analyze the expression of PDLIM1 in tissues. Enzyme-linked immunosorbent assay (ELISA) was employed to measure the autoantibody to PDLIM1 in 545 sera samples from 182 patients with OC, 181 patients with ovarian benign diseases, and 182 healthy controls.ResultsThe results of IHC indicated that 84.3% (236/280) OC tissues were positively stained with PDLIM1, while no positive staining was found in adjacent or normal ovarian tissues. The frequency of anti-PDLIM1 autoantibody was significantly higher in OC patients than that in healthy and ovarian benign controls in both training (n=122) and validation (n=423) sets. The area under the curves (AUCs) of anti-PDLIM1 autoantibody for discriminating OC from healthy controls were 0.765 in training set and 0.740 in validation set, and the AUC of anti-PDLIM1 autoantibody for discriminating OC from ovarian benign controls was 0.757 in validation set. Overall, it was able to distinguish 35.7% of OC, 40.6% of patients with early-stage, and 39.5% of patients with late-stage. When combined with CA125, the AUC increased to 0.846, and 79.2% of OC were detected, which is statistically higher than CA125 (61.7%) or anti-PDLIM1(35.7%) alone (p<0.001). Also, anti-PDLIM1 autoantibody could identify 15% (18/120) of patients that were negative with CA125 (CA125 <35 U/ml).ConclusionsThe anti-PDLIM1 autoantibody response in OC patients was positively correlated with PDLIM1 high expression in OC tissues, suggesting that the autoantibody against PDLIM1 might have the potential to be a novel serological biomarker of OC, serving as a complementary measure of CA125, which could improve the power of OC detection.

Disulfidptosis-related signature elucidates the prognostic, immunologic, and therapeutic characteristics in ovarian cancer

“…The role of MYL6 in OC is currently unknown, but it has been shown that MYL6 expression was upregulated in rhabdomyosarcoma ( Eichenmüller et al, 2007 ), and was negatively associated with cell migration in melanoma ( Vierthaler et al, 2022 ). Previous studies suggested that PDLIM1 was upregulated in OC ( Qiu et al, 2021 ), which was consistent with our findings ( Figure 6D ). PDLIM1 could inhibit tumor metastasis and EMT by interacting with E-cadherin/β-catenin adhesion complex, inhibiting the Hippo signaling pathway ( Chen et al, 2016 ; Huang et al, 2020 ).…”

Oridonin Induces Apoptosis in Esophageal Squamous Cell Carcinoma by Inhibiting Cytoskeletal Protein LASP1 and PDLIM1

“…This protein has a PDZ domain at the amino terminus, while at the carboxyl terminus is a LIM domain. PDLIM1 regulates the actin cytoskeleton organization and is involved in the cells’ morphological changes and migration [ 35 ]. The expression level of PDLIM1 impacts the assembly of focal adhesion.…”

Molecular Biomarkers for the Early Detection of Ovarian Cancer

“…Combining anti-BRCA1-associated RING domain 1 (BARD1) AABs and serum CA125 levels showed a sensitivity of 91% and a specificity of 95% among 741 samples [ 106 ]. Lastly, combining anti-PDZ and LIM domain 1 (PDLIM1) AABs and CA125 levels increased the AUC to 0.846, such that around 80% of patients could be detected [ 107 ].…”