Serum Autoantibodies against LRDD, STC1, and FOXA1 as Biomarkers in the Detection of Ovarian Cancer.

Yaru Duan,Cuipeng Qiu,Hua Ye,Peng Wang,Jianxiang Shi,Xiao Wang,Guiying Sun,Chi Cui,Liping Dai,Arianna Vignini

doi:10.1155/2022/6657820

Abstract

Purpose This study is aimed at evaluating serum autoantibodies against four tumor-associated antigens, including LRDD, STC1, FOXA1, and EDNRB, as biomarkers in the immunodiagnosis of ovarian cancer (OC). Methods The autoantibodies against LRDD, STC1, FOXA1, and EDNRB were measured using an enzyme-linked immunosorbent assay (ELISA) in 94 OC patients and 94 normal healthy controls (NHC) in the research group. In addition, the diagnostic values of different autoantibodies were validated in another independent validation group, which comprised 136 OC patients, 136 NHC, and 181 patients with benign ovarian diseases (BOD). Results In the research group, autoantibodies against LRDD, STC1, and FOXA1 had higher serum titer in OC patients than NHC (P < 0.001). The area under receiver operating characteristic curves (AUCs) of these three autoantibodies were 0.910, 0.879, and 0.817, respectively. In the validation group, they showed AUCs of 0.759, 0.762, and 0.817 and sensitivities of 49.3%, 42.7%, and 48.5%, respectively, at specificity over 90% for discriminating OC patients from NHC. For discriminating OC patients from BOD, they showed AUCs of 0.718, 0.729, and 0.814 and sensitivities of 47.1%, 39.0%, and 51.5%, respectively, at specificity over 90%. The parallel analyses demonstrated that the combination of anti-LRDD and anti-FOXA1 autoantibodies achieved the optimal diagnostic performance with the sensitivity of 58.1% at 87.5% specificity and accuracy of 72.8%. The positive rate of the optimal autoantibody panel improved from 62.4% to 87.1% when combined with CA125 in detecting OC patients. Conclusion Serum autoantibodies against LRDD, STC1, and FOXA1 have potential diagnostic values in detecting OC.

Highlights

Ovarian cancer (OC) remains the deadliest cancer in women worldwide
Due to the absence of specific symptoms at the early stage, the vast majority of OC patients were diagnosed at an advanced stage, and only 20% of OC patients were initially diagnosed at an early stage [5]
Sera from OC patients were obtained from a tertiary level hospital (Zhengzhou, China) from March 1, 2011, to April 30, 2012, and sera of normal healthy controls (NHC) were collected from the cardiovascular disease investigation project (Henan Province, China) without the benign ovarian disease (BOD) or disease associated with the immune system

Summary

Introduction

Ovarian cancer (OC) remains the deadliest cancer in women worldwide. There were an estimated 22,530 new cases and 13,980 deaths from OC in the United States in 2019, making it the leading cause of cancer deaths among gynecologic malignancies [1]. Advances in OC treatment significantly improved the five-year survival of OC patients over the last three decades, the overall cure rate remained less than 30% [2]. When the lesion is restricted within the ovaries, up to 90% of patients can be cured following routine surgery and chemotherapy, and the five-year survival rate is approximately 50% for disease limit to the pelvis (stage II) with treatment strategies [3]. The five-year survival rate for the disease beyond the pelvis (stage III-IV) is less than 20% [4]. Due to the absence of specific symptoms at the early stage, the vast majority of OC patients were diagnosed at an advanced stage (stage III or stage IV), and only 20% of OC patients were initially diagnosed at an early stage [5].

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Results