Recent research published in the British Journal of Cancer investigated several autoantibodies (AAb), antigens, and antigen-autoantibody (Ag-AAb) complexes for their ability to complement the biomarker CA125 in the early detection of ovarian cancer.
Study: Autoantibodies, Antigen-Autoantibody Complexes, and Antigens Complement CA125 for Early Detection of Ovarian Cancer. Image Source: mi_viri/Shutterstock.com
Ovarian cancer causes a significant number of deaths worldwide. In the US, a total of 19,880 women were diagnosed with ovarian cancer this year.
Recent advances in cytoreductive surgery and chemotherapy have improved survival rates in patients with epithelial ovarian cancer. However, survival chances largely depend on the stage of the disease at the time of detection.
If ovarian cancer is detected in stage 1, the patient has a five-year survival rate of over 90%. However, if the disease is detected in stage II, with the cancer confined to the pelvis, the chances of a five-year survival rate drop to 70%.
This percentage further decreases in stage III and eventually the cure rate drops to 20% if the disease is detected in stage IV. Computer-assisted studies estimated that early detection of ovarian cancer, i.e., stages I or II, could improve the cure rate by 10–30%.
Two US-based clinical studies, namely the United Kingdom Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) and the Normal Risk Ovarian Cancer Screening Study (NROSS), investigated the association between rising CA125 levels and the Risk of Ovarian Cancer Algorithm (ROCA).
It is noteworthy that the NROSS screening reduced the detection of advanced stage diseases (III-IV) by 34% compared to UKCTOCS controls. Therefore, early diagnosis of ovarian cancer is critical to improve the cure rate.
Elevated CA125 levels were found in sera of 60-70% of patients at early stages of epithelial ovarian cancer.
Increased sensitivity or higher detection rates could be achieved by the presence of additional biomarkers that complement CA125. In this regard, over 120 biomarkers have been identified, including antigens, AAb, and Ag-AAb.
AAb against antigens associated with ovarian cancer could be a promising candidate for enhancing the sensitivity of CA125. These could be easily produced in response to very low amounts of tumor-associated antigens.
This strategy could play a crucial role in the early detection of ovarian cancer, as AAb could be detected months or years before the increase in CA125.
About the Study
The current study compared panels of autoantibodies, Ag-AAb complexes, and ovarian cancer-associated antigens to determine the best complement of CA125 crucial for early detection of ovarian cancer.
The present study was conducted in collaboration with the National Cancer Institute Early Detection Research Network (EDRN).
A total of 26 different biomarkers were evaluated in a single set of serum samples in this study. Additionally, the effectiveness of five additional tests for Anti-TP53-AAb was examined using serum samples from healthy controls and patients with early and late-stage ovarian cancer.
The serum samples were used to identify the most promising classifier that includes the biomarkers in the group of CA125, human epididymis protein 4 (HE4), and HE4 Ag-AAb complexes. CA125 sensitivity alone confirmed this performance.
In the current study, increased CA 125 levels were detected with a specificity of 98% in the EDRN validation panel in 66% of patients with early-stage (I-II) ovarian cancer. This finding indicates the need for further improvement in the sensitivity of this panel.
HE4 is a protein produced by epithelial ovarian cancer cells. In the current study, HE4 detected 11% of ovarian cancer cases that were missed by CA125 in the entire EDRN set. About 19% of early-stage cases showed increased levels of HE4 Ag-AAb complexes.
The EDRN validation set showed an increased osteopontin level (OPN) in 13% of early-stage ovarian cancer cases. OPN is a glycoprotein synthesized by arterial smooth muscle cells, osteoblasts, various epithelial cells, macrophages, and activated T-cells in body fluids.
This protein is also overexpressed by cancer types originating in different regions, such as the ovary.
CA125 alone could only detect 62% of early-stage cases, while the panel detected 75%. Furthermore, a significant improvement in sensitivity for the EDRN validation set was achieved.
In the current study, increased anti-p53-AAb levels were observed in 20 to 25% of sera from ovarian cancer patients. The RAPID assay was more sensitive in detecting TP53-AAb in 22% of all cases.
In the early stage of ovarian cancer, an elevation was only observed for anti-CTAG1-AAb and anti-IL8-AAb.
CTAG1A recognized 8% of early-stage cases and 19% of late-stage cases with a specificity of 98%. Anti-IL-8-AAb showed higher sensitivity in detecting early ovarian cancer stages.
The classifier including all three autoantibodies and complexes, trained on EDRN set Anti-CTAG1, Anti-IL-8, and Anti-TP53, was able to detect 22% of early-stage cases with a specificity of 95%.
It should be noted that the sensitivity of three AAb did not surpass CA125 alone. However, AAb had an advantage over CA125.
The current study identified three biomarkers, HE4, HE4 Ag-AAb complexes, and OPN, which complement CA125. This strategy could improve the early detection of ovarian cancer with a specificity of 98%.
In some cases, there may be a potential lead time of over 18 months, which could be crucial for the effectiveness of treatment.