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. 2024 May 29;16(11):2060.
doi: 10.3390/cancers16112060.

Serum β-hCG as a Biomarker in Pancreatic Neuroendocrine Tumors: Rethinking Single-Analyte Approach

Paweł Komarnicki  1 , Paweł Gut  1 , Maja Cieślewicz  1 , Jan Musiałkiewicz  1 , Adam Maciejewski  1 , Michalina Czupińska  1 , George Mastorakos  2 , Marek Ruchała  1
Affiliations

Serum β-hCG as a Biomarker in Pancreatic Neuroendocrine Tumors: Rethinking Single-Analyte Approach

Paweł Komarnicki et al. Cancers (Basel). .

Abstract

Despite recent advances, neuroendocrine tumors (NETs) remain a challenging topic, due to their diversity and the lack of suitable biomarkers. Multianalyte assays and the shift to an omics-based approach improve on the conventional single-analyte strategy, albeit with their own drawbacks. We explored the potential of serum β-hCG as a biomarker for NETs and discussed its role in disease monitoring. We recruited 40 patients with non-functioning pancreatic NETs, all with liver metastases. Serum β-hCG concentrations were measured at 3-month intervals over 48 months. We performed a comparative and a repeated measures analysis of β-hCG depending on WHO grade (G1, G2), liver tumor burden (LTB; below 10%, 10-25%), and RECIST 1.1. (stable disease, progressive disease). Patients with progressive disease (p < 0.001), 10-25% LTB (p < 0.001) and WHO Grade 2 (p < 0.001) displayed higher β-hCG concentrations. Throughout the study, β-hCG concentrations consistently increased across the entire cohort. Delta β-hCG during the study period was greater in patients with 10-25% LTB (p < 0.001), progressive disease (p < 0.001), and G2 (p = 0.003). Serum β-hCG correlates with established indicators of malignancy and disease progression in metastatic NETs, supporting further studies as a monitoring and prognostic biomarker. Despite promising results from novel biomarkers, there is still a place for single-analyte assays in NETs.

Keywords: beta subunit; chorionic gonadotropin; human; neuroendocrine tumors; pancreatic neoplasms; tumor biomarkers.

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Conflict of interest statement

P.K.: honoraria from Novartis, Ipsen, clinical trial remuneration from Neurocrine Biosciences, Crinetics Pharmaceuticas, Ascendis Pharma; P.G.: honoraria from Novartis, Ipsen; M.C.: no conflict of interest; J.M.: honoraria from Novartis; A.M.: no conflict of interest; M.C.: no conflict of interest; G.M.: no conflict of interest; M.R.: honoraria from Novartis, Pfizer, Ipsen, Berlin-Chemie Menarini, Genzyme, Merck, IBSA. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Figures

Figure 1
Figure 1
The changes in β-hCG concentration over the 48-month study period depending on the treatment response according to RECIST 1.1. Mean β-hCG concentrations at a given time point determined by a sample number are presented as squares in patients with stable disease (SD) and circles in patients with progressive disease (PD). Vertical lines display 95% confidence intervals in each of the time points.
Figure 2
Figure 2
The changes in β-hCG concentration over the study period depending on tumor grading based on 2022 WHO criteria. Mean β-hCG concentrations at a given time point determined by a sample number are presented as squares in patients with G1 tumors and circles in patients with G2 tumors. Vertical lines display 95% confidence intervals in each of the time points.
Figure 3
Figure 3
The changes in β-hCG concentration over the 48-month study period in subgroups depending on liver tumor burden (LTB). Mean β-hCG concentrations at a given time point determined by a sample number are presented as squares in patients with LTB up to 10% and circles in patients with LTB between 10 and 25%. Vertical lines display 95% confidence intervals in each of the time points.
Figure 4
Figure 4
Delta β-hCG concentration in patients with stable disease (SD) and progressive disease (PD) according to RECIST 1.1. Delta β-hCG represents the individual variation between final and initial β-hCG concentrations (measured in mIU/mL). Box plots depict the interquartile range (Q1 to Q3), with the median highlighted by the internal line. The whiskers extend to the minimum and maximum values of the dataset.
Figure 5
Figure 5
Delta β-hCG concentration in patients with G1 and G2 tumors defined by 2022 WHO grading. Delta β-hCG represents the individual variation between final and initial β-hCG concentrations (measured in mIU/mL). Box plots depict the interquartile range (Q1 to Q3), with the median highlighted by the internal line. The whiskers extend to the minimum and maximum values of the dataset.
Figure 6
Figure 6
Delta β-hCG concentration in patients with up to 10% and 10–25% liver tumor burden (LTB). Delta β-hCG represents the individual variation between final and initial β-hCG concentrations (measured in mIU/mL). Box plots depict the interquartile range (Q1 to Q3), with the median highlighted by the internal line. The whiskers extend to the minimum and maximum values of the dataset.
Figure 7
Figure 7
ROC curve analysis illustrating the prognostic accuracy of initial β-hCG concentration on the occurrence of progressive disease. The dotted line represents the ROC curve if the classification is randomly estimated. The red dot indicates the optimal operating point for sensitivity and specificity.
Figure 8
Figure 8
Gantt diagrams illustrating study group characteristics and the overlap between variables in the study subjects.
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