Precise management of kidney cancer requires the identification of prognostic factors. hPG₈₀ (circulating progastrin) is a tumor promoting peptide present in the blood of patients with various cancers, including renal cell carcinoma (RCC). In this study, we evaluated the prognostic value of plasma hPG₈₀ in 143 prospectively collected patients with metastatic RCC (mRCC). The prognostic impact of hPG₈₀ levels on overall survival (OS) in mRCC patients after controlling for hPG₈₀ levels in non-cancer age matched controls was determined and compared to the International Metastatic Database Consortium (IMDC) risk model (good, intermediate, poor). ROC curves were used to evaluate the diagnostic accuracy of hPG₈₀ using the area under the curve (AUC). Our results showed that plasma hPG₈₀ was detected in 94% of mRCC patients. hPG₈₀ levels displayed high predictive accuracy with an AUC of 0.93 and 0.84 when compared to 18-25 year old controls and 50-80 year old controls, respectively. mRCC patients with high hPG₈₀ levels (>4.5 pM) had significantly lower OS compared to patients with low hPG₈₀ levels (<4.5 pM) (12 versus 31.2 months, respectively; p = 0.0031). Adding hPG₈₀ levels (score of 1 for patients having hPG₈₀ levels > 4.5 pM) to the six variables of the IMDC risk model showed a greater and significant difference in OS between the newly defined good-, intermediate- and poor-risk groups (p = 0.0003 compared to p = 0.0076). Finally, when patients with IMDC intermediate-risk group were further divided into two groups based on hPG₈₀ levels within these subgroups, increased OS were observed in patients with low hPG₈₀ levels (<4.5 pM). In conclusion, our data suggest that hPG₈₀ could be used for prognosticating survival in mRCC alone or integrated to the IMDC score (by adding a variable to the IMDC score or by substratifying the IMDC risk groups), be a prognostic biomarker in mRCC patients.

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