• Contract signed with: 
    Les Hospices Civils de Lyon

  • Principal investigator:
    Benoît You

hPG80 is a biomarker for patients treated for gastro-intestinal cancers.

A retrospective study on the BIG-RENAPE cohort.

Last updated: August 3, 2020

1

Scientific context

There is a need for early predictor of clinical benefits able to compress the time line required to evaluate new treatments (1).

 

Moreover, peritoneal carcinomatosis frequently developed by gastrointestinal cancer patients is poorly assessable using conventional imaging (2).

 

In addition, the traditional morphological RECIST criteria were found not adequate for assessing treatment efficacy with anti-angiogenic drugs (3).

 

Strategies that may help characterize tumor size changes or treatment efficacy during treatment are to be developed. If some serum markers (liquid biopsy) were shown to be surrogate markers of treatment efficacy, they could be used to identify the patients who benefit the most from the treatment or who may be candidates for iterative surgery (4)

2

hPG80, a new blood based biomarker

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. 

3

Objective

Assessment of hPG80 usability in follow up with surgery. 

4

Patients

Patients recorded in prospective BIG-RENAPE project database, NCT02823860 (Lyon, FRANCE). Biological data were extracted from the data base.

 

Analysis was performed in HCL Lyon Sud facility (Pierre-Bénite, FRANCE).

 

194 patients with peritoneal involvements from gastrointestinal cancers, treated with peri-operative chemotherapy regimens and cytoreductive surgery. 

Blood samples were collected at inclusion (n=194) and between 8 and 24 hours after cytoreductive surgery, performed with or without hyperthermic intraperitoneal chemotherapy (HIPEC) (n=85).

5

Results

In this cohort, median hPG80 significantly decreased from inclusion to the post-operative period from 3.08 to 1.57 pM[AP1] , p<0.0001 with two-tailed unpaired Mann-Whitney test. 

The individual curves showed that 74.2% of patients had hPG80 titer declines >25%. The remaining patients experienced stable concentrations (16.1% of patients), or hPG80 level increases >25% (9.7% of patients). 

b&w_carcinome-peritoneal.png
Evo_carcinose-peritoneal.png

6

Conclusion

hPG80 is a good biomarker for peritoneal carcinomatosis patients to assess surgery efficacy.

 

Levels are significantly decreased after surgery and individual follow-up shows that minimal residual disease might be questioned via the presence of hPG80 in the blood. 

These results have been published in You et al, EBioMedicine, 2020.

7

Bibliography

1. Kola I, Landis J: Can the pharmaceutical industry reduce attrition rates? Nat Rev Drug Discov 3:711-5, 2004.


2. Laghi A, Bellini D, Rengo M, et al: Diagnostic performance of computed tomography and

magnetic resonance imaging for detecting peritoneal metastases: systematic review and meta-analysis. 

Radiol Med 122:1-15, 2017.

3. Nishino M, Jagannathan JP, Krajewski KM, et al: Personalized tumor response assessment in the era of molecular medicine: cancer-specific and therapy-specific response criteria to complement pitfalls of RECIST. AJR Am J Roentgenol 198:737-45.

4. McMullen JRW, Selleck M, Wall NR, et al: Peritoneal carcinomatosis: limits of diagnosis and the case for liquid biopsy. Oncotarget 8:43481-43490, 2017.

5. You B, Mercier F, Assenat E, et al : The oncogenic and druggable hPG80 (Progastrin) is overexpressed in multiple cancers and detected in the blood of patients. EBioMedicine 51:102574, 2020.