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.
Highlights
Ovarian cancer (OC) is one of the most common cancer among women, with approximately 313,959 new diagnoses and 207,252 deaths worldwide in 2020 [1]
We aim to explore the occurrence and presentation level of anti-PDLIM1 autoantibodies in the sera of patients with ovarian cancer and further to evaluate its potential as a biomarker for the detection of OC
OC tissue microarray consisting of tissues from 294 OC patients (14 of 294 were invalid), 20 adjacent tissues, and 8 normal ovarian tissues was obtained from Shanxi Avila Biotechnology Ltd., Co. (Xian, China), and duplicate cores per case of cancer to make sure of a solid result
Summary
Ovarian cancer (OC) is one of the most common cancer among women, with approximately 313,959 new diagnoses and 207,252 deaths worldwide in 2020 [1]. The measurement of CA125 level has been embraced by primary care for ovarian cancer, but the measurements with better sensitivity and specificity are especially in need for early disease [5]. To address this issue, substantial work needs to be put into the exploration of novel biomarkers that could improve early diagnosis and treatment effect. The detection of autoantibodies (AAbs) triggered by tumorassociated antigens (TAAs) is showing great potential for the development of blood-based biomarkers [6, 7]. Serum 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)
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