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

Simple Summary Current blood-based biomarkers for neuroendocrine neoplasms (NENs) lack both sensitivity and specificity. Human circulating progastrin (hPG(80)) can be easily measured in plasma by ELISA. This study is the first to examine hPG(80) in NENs. The study demonstrated increased levels of hPG(80) in all sub-types of NENs, with a high sensitivity and specificity demonstrated. Plasma hPG(80) 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 hPG(80) as a means of monitoring disease (NCT04750954). Current blood-based biomarkers for neuroendocrine neoplasms (NENs) lack both sensitivity and specificity. Human circulating progastrin (hPG(80)) is a novel biomarker that can be easily measured in plasma by ELISA. This study is the first to examine hPG(80) in NENs. Plasma hPG(80) was quantified from 95 stage IV NEN patients, using DxPG(80) technology (ECS Progastrin, Switzerland) and compared with hPG(80) concentrations in two cohorts of healthy donor controls aged 50-80 (n = 252) and 18-25 (n = 137). Median hPG(80) 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 hPG(80) 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 hPG(80) 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 hPG(80) as a means of monitoring disease (NCT04750954).

Automated summary

Current blood-based biomarkers for neuroendocrine neoplasms lack sensitivity and specificity. This study examined the potential of human circulating progastrin as a biomarker for neuroendocrine neoplasms. The results showed that levels of circulating progastrin were significantly higher in neuroendocrine neoplasms patients and demonstrated high sensitivity and specificity. Plasma circulating progastrin may be a diagnostic blood biomarker for both low- and high-grade neuroendocrine neoplasms, but further research is needed.