Abstract

Simple SummaryCurrent blood-based biomarkers for neuroendocrine neoplasms (NENs) lack both sensitivity and specificity. Human circulating progastrin (hPG80) can be easily measured in plasma by ELISA. This study is the first to examine hPG80 in NENs. The study demonstrated increased levels of hPG80 in all sub-types of NENs, with a high sensitivity and specificity demonstrated. 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).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).

Highlights

  • Neuroendocrine neoplasms (NENs) are heterogeneous tumors that originate from various organs and are of variable aggressiveness based on grade and morphology

  • A common unifying factor for both neuroendocrine tumors (NET) and neuroendocrine carcinoma (NEC) is lack of reliable blood-based diagnostic biomarker. hPG80 is a pan tumor biomarker that has been found to be over-expressed in multiple malignancies. hPG80 synthesis is product of overexpression of GAST gene in cancer cells and human circulating progastrin can be measured accurately with help of DxPG80 Enzyme-Linked Immunosorbent Assay (ELISA) based test [8,16]

  • We investigated the diagnostic value of plasma hPG80 in patients with both low- and high-grade neuroendocrine neoplasms (NENs)

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Summary

Introduction

Neuroendocrine neoplasms (NENs) are heterogeneous tumors that originate from various organs and are of variable aggressiveness based on grade and morphology. The incidence of neuroendocrine tumors (NETs) has increased 6.4-fold, making NETs the second most prevalent gastrointestinal malignancies after colorectal cancer [1,2]. Progastrin esnt accumulate in antral G cells, as compared to G34-Gly and fully matured gastrin [5]. Progastrin is not detectable in the blood in normal subjects, barring few exceptions. As a result of GAST gene expression, high hPG80 levels are detected in blood of cancer patients [7,8,9]. We conducted a pilot study to test the presence of hPG80 in neuroendocrine neoplasms

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