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
. 2022 Feb 9;14(4):863.
doi: 10.3390/cancers14040863.

hPG80 (Circulating Progastrin), a Novel Blood-Based Biomarker for Detection of Poorly Differentiated Neuroendocrine Carcinoma and Well Differentiated Neuroendocrine Tumors

Affiliations

hPG80 (Circulating Progastrin), a Novel Blood-Based Biomarker for Detection of Poorly Differentiated Neuroendocrine Carcinoma and Well Differentiated Neuroendocrine Tumors

Aman Chauhan et al. Cancers (Basel). .

Abstract

Current blood-based biomarkers for neuroendocrine neoplasms (NENs) lack both sensitivity and specificity. Human circulating progastrin (hPG80) is a novel biomarker that can be easily measured in plasma by ELISA. This study is the first to examine hPG80 in NENs. Plasma hPG80 was quantified from 95 stage IV NEN patients, using DxPG80 technology (ECS Progastrin, Switzerland) and compared with hPG80 concentrations in two cohorts of healthy donor controls aged 50-80 (n = 252) and 18-25 (n = 137). Median hPG80 in NENs patients was 5.54 pM compared to 1.5 pM for the 50-80 controls and 0.29 pM the 18-25 cohort (p < 0.0001). Subgroup analysis revealed median hPG80 levels significantly higher than for either control cohort in neuroendocrine carcinoma (NEC; n = 25) and neuroendocrine tumors (NET; n = 70) including the small-cell lung cancer (SCLC) sub-cohort (n = 13). Diagnostic accuracy, estimated by AUCs, was high for NENs, as well as both sub-groups (NEC/NET) when compared to the younger and older control groups. Plasma hPG80 in NENs may be a diagnostic blood biomarker for both low- and high-grade NENs; further study is warranted. A prospective multi-center trial is ongoing in NET to evaluate hPG80 as a means of monitoring disease (NCT04750954).

Keywords: blood-based diagnostic biomarker; circulating progastrin; hPG80; neuroendocrine carcinoma; neuroendocrine neoplasms; neuroendocrine tumors; small-cell carcinoma.

PubMed Disclaimer

Conflict of interest statement

The employees of ECS Progastrin are A.P., Y.M., B.V. and D.J. Those with no competing interest are J.K., S.A., L.P., M.S., B.M.E. and L.A.

Figures

Figure 1
Figure 1
Diagnostic performance of hPG80 in (A) NENs, NEC and NET patient cohorts, (B) by tumor grade, (C) by tumor site as compared to the 18–25-year-old and 50–80-year-old.
Figure 2
Figure 2
Diagnostic accuracy, estimated by the Receiver Operator Characteristic (ROC) Area Under the Curve (AUC)s, is 0.89 for all NENs (A), 0.92 for NECs (B), and 0.87 for NETs (C) when compared to the young 18–25 y control group (square); for the older 50–80 y cohort, the values were 0.75 for all NENs (A), 0.75 for NECs (B), and 0.74 for NETs (C) (triangles).
Figure 3
Figure 3
Sensitivity of hPG80 in the all-patient (neuroendocrine neoplasm) cohorts with a specificity set at 90% as compared to (A) 18–25 y control group and (B) 50–80 y control group.

References

    1. Chauhan A., Kohn E., Del Rivero J. Neuroendocrine Tumors-Less Well Known, Often Misunderstood, and Rapidly Growing in Incidence. JAMA Oncol. 2020;6:21–22. doi: 10.1001/jamaoncol.2019.4568. - DOI - PMC - PubMed
    1. Dasari A., Shen C., Halperin D., Zhao B., Zhou S., Xu Y., Shih T., Yao J.C. Trends in the Incidence, Prevalence, and Survival Outcomes in Patients with Neuroendocrine Tumors in the United States. JAMA Oncol. 2017;3:1335–1342. doi: 10.1001/jamaoncol.2017.0589. - DOI - PMC - PubMed
    1. Oberg K., Modlin I.M., De Herder W., Pavel M., Klimstra D., Frilling A., Metz D.C., Heaney A., Kwekkeboom D., Strosberg J., et al. Consensus on biomarkers for neuroendocrine tumour disease. Lancet Oncol. 2015;16:e435–e446. doi: 10.1016/S1470-2045(15)00186-2. - DOI - PMC - PubMed
    1. Rehfeld J.F., Zhu X., Norrbom C., Bundgaard J.R., Johnsen A.H., Nielsen J.E., Vikesaa J., Stein J., Dey A., Steiner D.F., et al. Prohormone convertases 1/3 and 2 together orchestrate the site-specific cleavages of progastrin to release gastrin-34 and gastrin-17. Biochem. J. 2008;415:35–43. doi: 10.1042/BJ20080881. - DOI - PubMed
    1. Varro A., Voronina S., Dockray G.J. Pathways of processing of the gastrin precursor in rat antral mucosa. J. Clin. Investig. 1995;95:1642–1649. doi: 10.1172/JCI117839. - DOI - PMC - PubMed

Associated data

LinkOut - more resources