Unveiling Circulating Targets in Pancreatic Cancer: Insights from Proteogenomic Evidence and Clinical Cohorts

Published: 22 October 2024| Version 1 | DOI: 10.17632/jyyvrrsz44.1
Contributor:
Haokang Feng

Description

Pancreatic cancer (PC), characterized by the absence of effective biomarkers and therapies, remains highly fatal. Data regarding the correlations between PC risk and individual plasma proteome known for minimally invasive biomarkers, are scarce. Here, we analyzed 1,345 human plasma proteins using Proteome-Wide Association Studies, identifying 78 proteins significantly associated with PC risk. Of these, four proteins (ROR1, FN1, APOA5, and ABO) showed the most substantial causal link to PC, confirmed through Mendelian Randomization and Colocalization analyses. Data from two clinical cohorts further demonstrated that FN1 and ABO were notably overexpressed in both blood and tumor samples from PC patients, compared to healthy controls or para-tumor tissues. Additionally, elevated FN1 and ABO levels correlated with shorter median survival in patients. Multiple drugs targeting FN1 or ROR1 are available or in clinical trials. These findings suggest that plasma protein FN1 associated with PC hold potential as both prognostic biomarkers and therapeutic targets. The raw immunostaining and ELISA data from our center’s cohort have been uploaded to the Mendeley database.

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Institutions

Fudan University

Categories

Pancreatic Cancer, Mendelian Randomization

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