Liquid biopsy will become the new standard for diagnosing tumors and monitoring treatments (Bardelli et al, Cancer Cell, 2017).
Plasma hPG80 detection assay falls within this framework. ECS-Progastrin has developed a sandwich ELISA assay, which is reliable, simple, robust, inexpensive and used in almost all laboratories and hospitals around the world.
Using our ELISA assay, we have already demonstrated the presence of hPG80 on a first cohort of colorectal cancer patients, mainly patients in late stages (more than 150 patients in stage 3 and 4) and some early stages (20 patients in stage 1 and 2).
Whatever the stage, hPG80 is detected with very good sensitivity.
Similarly, we showed the presence of hPG80 in the blood of 58 patients with adenomatous polyps, with very good sensitivity.
With regard to hyperplastic polyps, we were only able to analyze the presence of hPG80 in a limited number of cases (n = 10). hPG80 was not detected in any of these patients.
This project aims to increase the number of patients with stage I and II colorectal cancer or with hyperplastic or adenomatous polyps, for whom we will measure plasma hPG80 levels.
This will clarify the value of hPG80 as a biomarker for patients with early stages colorectal cancer and for patients with polyps.
Non Pathologic Condition
hPG80 is not found in the blood
of healthy people.
When progastrin is maturated into gastrin, it is released from the cells.
When gastrin is produced by the G cells of the stomach antrum, it plays its role to control acidic secretions during digestion.
Pathologic Condition
hPG80 is detected in the blood
of cancer patients.
When progastrin is not maturated into gastrin, it is released from the cells as such and named hPG80.
This only happens in tumor cells, whatever the tumor cell: progastrin becomes a circulating protein, hPG80, which can be detected in the blood of cancer patients.
Show the presence or absence of hPG80 in the blood of patients with adenomatous polyps or with early colorectal cancer and establish the discriminative accuracy of hPG80 as a biomarker of these pathologies.
Correlate hPG80 levels with cancer stage.
Cancer patients samples were obtained from SIRIC (Montpellier, FRANCE).
Analyzes were performed within Eurobiodev facility (Montpellier, FRANCE).
This retrospective study was approved by Montpellier cancer institute scientific council (ICM-CORT).
Approval date and number: 13/11/2017 (ICM-CORT-2017-23) 96 patients were included in the study.
Healthy blood donors samples were obtained from the French blood agency (EFS, Montpellier, FRANCE).
Analyzes were performed within Eurobiodev facility (Montpellier, FRANCE).
Approval date and number: 17/07/2017 (21PLER2017-0019) 80 non-fasting healthy donors were included in the study.
The presence of hPG80 in early colorectal cancer stages was confirmed.
Median hPG80 levels in CRC early stages patients were significantly higher than those in healthy blood donors (p< 0.0001) (Figure 1).
Median hPG80 concentration was 0.23 pM (IQR 0.00-0.80 pM) in control population, against 2.315 pM (IQR 0.64-3.69 pM), 2.26 pM (IQR 0.70-9.60 pM), and 5.46 pM (IQR 1.67-9.945 pM) in patients with preneoplasic lesions, CRC stage 1 or CRC stage 2, respectively (Figure 1).
There is a significant increase in hPG80 blood levels from adenomatous polyps to stage 2 colorectal cancer.
Figure 1.
Comparison of hPG80 concentrations between healthy blood donors (n=80) and cancers patients, preneoplasic lesions (n=24), stage 1 CRC (n=23), stage 2 CRC (n=49).
Representation in box and Whiskers (2.5-97.5 percentile, dots are outliers).
Two-tailed Mann-Whitney test; ***, p< 0.001; *, p< 0.05.
The diagnostic discriminative accuracy of hPG80 levels was estimated using Receiver Operating Characteristics (ROC) curves in patients with preneoplasic lesions, patients with stage 1 CRC or patients with stage 2 CRC, compared to healthy blood donors control cohort.
The diagnostic discriminative accuracy estimated by the ROC AUC were 0.80 (95% CI: 0.69 to 0.91) for patients with preneoplasic lesions; 0.825 (95% CI: 0.72 to 0.93) for patients with stage 1 CRC; and 0.89 (95% CI: 0.82 to 0.95) for patients with stage 2 CRC, compared to the blood donor control group (Figures 2, 3 and 4).
hPG80 is detected with a very good accuracy in the blood of patients with an adenomatous polyp or with a stage 1 or 2 colorectal cancer.