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

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.

Comprehensive single-cell analysis reveals heterogeneity of fibroblast subpopulations in ovarian cancer tissue microenvironment

“…This transcription factor was also notably activated in malignant cells. Previous studies have established FOXA1 as a serum biomarker for ovarian cancer, with overexpression evident in ovarian tumor tissue [ 55 ]. Its role in influencing the progression and prognosis of breast and prostate cancer has also been documented, suggesting a notable influence on cancer biology [ 56 , 57 ].…”

Cancer-associated mesothelial cell–derived ANGPTL4 and STC1 promote the early steps of ovarian cancer metastasis

“…STC1 is also secreted by multiple cell types in the tumor microenvironment, including cancer cells, cancer associated fibroblasts, macrophages and adipocytes (48,(50)(51)(52). STC1 reversely correlates with checkpoint therapy efficacy in patients with melanoma and lung cancer and is associated with poor patient survival across multiple cancer types (49,(53)(54)(55)(56)(57)(58)(59)(60). Using RNAi technology and neutralizing antibodies, we discovered that ANGPTL4 and STC1 differentially regulated cancer-associated mesothelial cell tumor-promoting functions, and that neutralization of ANGPTL4 alone or in combination with STC1 prevented metastasis.…”

The stromal-tumor amplifying STC1-Notch1 feedforward signal promotes the stemness of hepatocellular carcinoma

“…STC1 was found to be a biomarker in many diseases [52][53][54][55] . In this study, we found that STC1 was highly expressed in HCC and was closely correlated with poor prognosis in HCC patients.…”