Progastrin, a New Blood Biomarker for Multiple Cancers Allowing a New Strategy for Screening, Early Detection and Monitoring

Background: The majority of cancers evolve for years before becoming symptomatic. But once symptomatic, it is often too late for the patients to be cured. It is thus of paramount importance to improve early cancer screening in the general population as well as in genetically predisposed individuals. Moreover, although there is an undeniable progress in treatments, in particular in the immuno-oncology field, there is a growing need for circulating biomarkers to monitor treatment efficacy to better impact patient health and social economics. Aim: Progastrin (PG) is abnormally released in the blood of patients with colorectal cancer (CRC), as the gene coding for PG is a direct target of the WNT/β-catenin oncogenic pathway involved in tumorigenesis of many organs and activated from the very first steps of tumorigenesis, allowing the detection of PG in early stage cancers. The objective was to assess the diagnostic value of PG in a series of different types of cancers (early and advanced stages), as well as the role of PG as a circulating biomarker for treatment follow-up in patients with peritoneal carcinomatosis, a metastatic disease where imaging monitoring is impossible (due to the small size of lesions). Methods: Progastrin was measured in plasma EDTA samples using the ELISA cancerREAD technology. For the evaluation of PG in cancer patients, 673 samples were collected for comparison with 119 healthy volunteers. For the follow-up monitoring, patients were enrolled during management of peritoneal carcinomatosis (before or after neoadjuvant chemotherapy, or surgery). The diagnostic value of PG concentrations at inclusion in 190 GI cancer patients was assessed against 80 control samples. Results: Progastrin was detected in 77% of cancer patients, all cancers combined. The diagnosis area under the ROC curve of PG was 0.9114, P < 0.0001. Sensitivity ranged from 71% (breast cancer) to 87% (skin melanoma). All the 15 different types of cancers tested were positive. Early stage detection was assessed for colorectal and breast cancers with a sensitivity of 62.5% for adenomatous polyps, and 68.2% for stage 0 and I breast cancers. Sensitivity increased up to 82% for stage II colorectal cancer and to 78% for stage II-IV breast cancers. For the follow-up of peritoneal carcinomatosis patients, median PG levels decreased whatever the GI subtype with sequential treatments from 4.4 pM at inclusion time, to 1.3 after adjuvant chemotherapy. A trend for better PFS was observed in patients with PG decline after surgery. Conclusion: Progastrin assay is a simple and inexpensive blood test exhibiting high diagnostic accuracy for multiple gastro-intestinal, gynecologic, skin cancers. It may be used for cancer screening before tumor localization. It also exhibits promising therapeutic monitoring value during treatment in advanced CRC patients. Assessment of PG value as a multitumor screening biomarker, and as a monitoring test, is ongoing.