Progastrin: A new specific early cancer screening biomarker.

Abstract

11545 Background: One in two people will be diagnosed with cancer during his/her lifetime. Because we are lacking effective screening tests, most cancers are detected in late stages, when survival rates are very low. Here, we show the development of the first early cancer screening test for multiple cancers using progastrin (PG) as biomarker. The gene coding for PG is a target gene of the Wnt oncogenic pathway that is activated in almost all type of cancers, at the earliest stages of development. We showed that the neutralization of PG by a specific humanized antibody could be used for colorectal cancer treatment. Moreover, as PG is secreted by cancer cells, we can specifically detect it in the blood of persons having a cancer at early stage. Methods: Antibodies directed against PG were produced and selected for target specificity and affinity. ELISA is the most reliable assay to detect biomarker on the blood. Hence, selected antibodies were used to set up an ELISA sandwich to detect PG in the blood of patients with various types of cancers and at various stages. Results: We first set up a prototype ELISA using polyclonal antibodies. We validated our test using 223 blood samples from patients with polyps and colorectal cancers at various stages for which we observed an increased levels of PG. Then, we showed the presence of PG in the blood of 212 patients with other types of cancer, including liver, pancreatic and breast cancers, confirming that PG could be used as a biomarker for multiple types of cancers. Next, we set up our industrial ELISA using polyclonal and monoclonal antibodies called DECODE Lab and tested 245 new blood samples from patients with various types of cancer including early stages. Strikingly, using our test we were able to detect breast (AUC = 0.9638; sensitivity 70%), colorectal (AUC = 0.9635; sensitivity 73%), melanoma (AUC = 0.9882; sensitivity 87%) and cervix utery (AUC = 0.9827; sensitivity 84%) all stages combined with a high specificity of 97.5%. Finally, for early stage patients with melanoma and breast cancer, we had a sensitivity of 68% and 81% respectively. Conclusions: Taken together, the results presented here show that PG is a reliable biomarker for early cancer screening. The ELISA test that we developed is very efficient and now available for the clinic.