Résumé
Background and aims: Alpha-fetoprotein (AFP) is the most widely used biomarker for hepatocellular carcinoma (HCC) patient follow-up, even though around 30% of HCC do not express AFP and its capacity to reliably monitor treatment efficacy is questioned. Interestingly, progastrin, a direct target of the oncogenic Wnt/beta-catenin pathway that is commonly activated in HCC, is secreted as such from tumor cells of various origin, from the very first steps of tumorigenesis. Here, we show the first study evaluating the potency of blood progastrin levels to monitor treatment efficacy and compared it with AFP.
Methods: Progastrin was quantified in the blood of 87 patients with HCC (focal (n=23), locally advanced (n=49) or metastatic (n=19). AFP was available in 79 patients. The cancerREAD technology (CE marked since 2017) specifically designed to detect progastrin with a high sensitivity and not any maturation products such as gastrin or gastrin glycine extended was used to assay progastrin in the blood. Patients received a systemic (nevaxar, tepotinib, regorafenib, nivolumab, anti FGR, or carbozantinib) and/or a local treatment. Variations in the levels of progastrin and AFP were analyzed in relationship with evolution of the disease: progression, decrease, stable, in remission, without taking into account the different treatment regimens.
Results: Progastrin was detected in 80% of the patients (cut-off value 1 pM, range 0 to 75.9 pM, mean value +/- SE 16.29 +/-1.97 pM). Patients in remission had a significantly lower blood progastrin compared to focal (p=0.019), locally advanced (p=0.0001) or metastatic HCC (p=0.015) (Focal 16.96 +/- 4.82 pM; locally advanced 18.57 +/- 2.75 pM; metastatic 17.81 +/- 4.9 pM; in remission 4.89 +/- 1.05 pM). AFP was above 10 ng/ml (a common threshold value) in 59.4% of the samples; levels of progastrin were not statistically correlated with those of AFP. Blood samples for follow-up of treatment were available for 48 patients. Compared to AFP, progastrin was a better biomarker of the evolution of the disease in 35.1% of the patients. Both biomarkers were equivalent in 32.4% and none were good in 10.8%. AFP was better than progastrin only in 21.6%.
Conclusion: Thus, and for the first time, we showed that not only progastrin is a better blood biomarker than AFP to detect HCC but also is better for the follow-up of HCC patients, whatever the treatment of the patient. This is the first study that shows the potential of progastrin (alone or in combination with AFP) as a tool for follow-up of cancer treatment efficacy.
Citation Format: Alexandre Prieur, Marie Dupuy, Dominique Joubert, Eric Assenat. Progastrin a new biomarker for hepatocellular cancer patient follow-up [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2222.