Diagnostic value of hPG₈₀, as a new multi-cancer blood biomarker, in 16 different cancers: Results of the ONCOPRO prospective study.

3033 Background: hPG 80 (also called circulating progastrin) has been described as a promising multi-cancer blood biomarker. Indeed, hPG 80 is released from cancer cells to blood at the early steps of tumorigenesis due to WNT pathway activation (You et al eBioMedicine 2020). ONCOPRO study was designed to prospectively assess the hPG 80 diagnostic & clinical utility in patients with 16 types of cancers. Methods: ONCOPRO study (NCT03787056) was a large prospective case-control study led in Lyon University Hospital (France), designed to assess the diagnostic, and monitoring value of hPG80 blood titers in 420 patients with 16 newly diagnosed cancers. hPG 80 was measured using kit DxPG80.Lab (Biodena care) at diagnosis, and then at each cycle/visit until recurrence for the curative cohorts, or for 3 treatment lines for the non-curative cohorts. The diagnostic value of hPG 80 (primary endpoint) was assessed by comparing the hPG 80 baseline titers measured in cancer patients to those of 330 healthy volunteers recruited in parallel (age & sex ratios matched with the cancer group), with a sample size calculated for precision of ±0.23 for ROC AUC. Results: Out of 499 cancer patients enrolled between December 2018 and June 2022, 419 were assessable in 16 cancer cohorts (NSCLC & SCLC: n=70; Breast: n=50; Renal: n=50; Prostate: n=50; Liver: n=50; Head&Neck: n=49; Hepatocellular carcinoma (HCC): n=50; Colorectal: n=10; Thyroid: n=10; Pancreas: n=14; Ovarian: n=10; Glioblastoma: n=10; Endometrial: n=10; Bladder: n=10; Superficial oesophago-gastric: n=10; Lymphoma: n=10; Gastric: n=10). The median age of cancer patients was 66 [IQR: 58-73], with 60% men. hPG 80 concentration was significantly higher in cancer patients than in healthy subjects (median, 3.8 vs 2.0 pM, P < 0.001). It was not impacted by renal/liver, or CRP level, but slightly linked to age. hPG 80 titer was found stable on a 24h-hour period. The global diagnostic accuracy in cancer patients / control was ROC AUC, 0.63 [0.59-0.67] in the whole population. The highest diagnostic accuracy was seen in patients with lung cancer (AUC, 0.75 [0.68-0.82]; Sensitivity (Se)/Specificity (Sp) 0.49/0.90 for hPG 80 >7.73 pM) and HCC (AUC, 0.75, 95% CI 0.66-083; Se/Sp 0.48/0.90 for hPG80 > 7.73 pM). Conclusions: This large prospective study confirms that cancer patients have significantly higher blood concentration of hPG 80 than healthy subjects. The data about the different cohorts will guide the future development of hPG 80 . Strong diagnostic accuracy was seen for lung cancers and HCC, with specificity > 90%. The screening programs of these cancers could be enriched by this simple blood hPG 80 ELISA assay, for complementing imaging limited specificity. Clinical trial information: NCT03787056 .