Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2019 Jun;12(6):391-400.
doi: 10.1158/1940-6207.CAPR-18-0377. Epub 2019 Apr 9.

Complementary Longitudinal Serum Biomarkers to CA125 for Early Detection of Ovarian Cancer

Archana R Simmons  1 , Evangelia Ourania Fourkala  2 , Aleksandra Gentry-Maharaj  2 , Andy Ryan  2 , Margie N Sutton  1 , Keith Baggerly  3 , Hui Zheng  4 , Karen H Lu  5 , Ian Jacobs  2 , Steven Skates  4 , Usha Menon  2 , Robert C Bast Jr  6
Affiliations

Complementary Longitudinal Serum Biomarkers to CA125 for Early Detection of Ovarian Cancer

Archana R Simmons et al. Cancer Prev Res (Phila). 2019 Jun.

Abstract

Early detection of ovarian cancer has the potential to impact mortality. A multimodal screening strategy where rising CA125 values over time, analyzed with the risk of ovarian cancer algorithm (ROCA), triggers transvaginal sonography and possible surgery has high sensitivity and specificity, but still fails to detect the 20% of early-stage cases that do not express CA125. Use of multiple biomarkers could detect cases missed by CA125. We have studied the sensitivity and lead time of a multi-marker panel (CA125, HE4, MMP-7, and CA 72-4) compared with CA125 alone. We used PRoBE design principles to select preclinical longitudinal specimens from 75 women (50 screen-positive, 25 screen-negative) who developed invasive epithelial ovarian cancer (3-5 serial specimens each) and 547 corresponding healthy controls (1-10 serial specimens each) from the ovarian cancer screening trial, UKCTOCS, in a blinded fashion. We measured the multi-marker concentrations in ultra-low serum volumes (16 μL) utilizing multiplexed bead-based immunoassays with low detection limits, high inter- and intra-assay precision, negligible cross-reactivity, and good correlation with standard immunoassays. While, at least one of the complementary biomarkers rose with CA125 in 44% (22/50) of screen-positive cases, there was no advantage in lead time over CA125. Therefore, we developed single-marker longitudinal algorithms (ROCA-like) to determine the presence of a change point to distinguish between the cases and controls. Using these algorithms, at 98% specificity, HE4 and CA72-4 identified 16% (4/25) of screen-negative cases, while MMP-7 identified none. Taken together, HE4 and CA72-4 show promise as complementary biomarkers to CA125 for longitudinal screening.

PubMed Disclaimer

Conflict of interest statement

Disclosure of Potential Conflicts of interest: Dr. Bast receives royalties from Fujirebio Diagnostics Inc., for the discovery of CA125. Prof Menon has shares awarded to her by UCL in Abcodia Pvt Ltd.

Figures

Figure 1:
Figure 1:
Comparison of multiplex immunoassays for CA125, HE4, MMP-7 and CA72-4 against ELISA methods utilizing early stage ovarian cancer patient samples show good correlation between methods.
Figure 2:
Figure 2:
Representative multi-marker longitudinal profiles of a CA125 screen-positive case (A), Control (B) and CA125 screen-negative case (C).
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2018. CA Cancer J Clin 2018;68(1):7–30 doi 10.3322/caac.21442. - DOI - PubMed
    1. Patriotis C, Simmons A, Lu KH, Bast RC and Skates SJ Ovarian Cancer In: Srivastava S, editor. Biomarkers in Cancer Screening and Early Detection Chichester, UK: : John Wiley & Sons, Ltd; 2017.
    1. Force USPST, Grossman DC, Curry SJ, Owens DK, Barry MJ, Davidson KW, et al. Screening for Ovarian Cancer: US Preventive Services Task Force Recommendation Statement. JAMA 2018;319(6):588–94 doi 10.1001/jama.2017.21926. - DOI - PubMed
    1. Pignata S, Cannella L, Leopardo D, Bruni GS, Facchini G, Pisano C. Follow-up with CA125 after primary therapy of advanced ovarian cancer: in favor of continuing to prescribe CA125 during follow-up. Ann Oncol 2011;22 Suppl 8:viii40–viii4 doi 10.1093/annonc/mdr470. - DOI - PubMed
    1. Rauh-Hain JA, Krivak TC, Del Carmen MG, Olawaiye AB. Ovarian cancer screening and early detection in the general population. Rev Obstet Gynecol 2011;4(1):15–21. - PMC - PubMed

Publication types

MeSH terms