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A Promising Biomarker and Therapeutic Target in Patients with Advanced PDAC: The Stromal Protein βig-h3
Christelle de la Fouchardière1,2,3, Pia Gamradt1,2,3, Sylvie Chabaud3
1Cancer Research Center of Lyon, UMR INSERM 1052, CNRS 5286, F-69373 Lyon, France.
Abstract:
With an overall survival rate of 2-9% at 5 years, pancreatic ductal adenocarcinoma (PDAC) is currently the fourth leading cause of cancer-related deaths in the industrialized world and is predicted to become the second by 2030. Owing to often late diagnosis and rare actionable molecular alterations, PDAC has not yet benefited from the recent therapeutic advances that immune checkpoint inhibitors (ICI) have provided in other cancer types, except in specific subgroups of patients presenting with tumors with high mutational burden (TMB) or microsatellite instability (MSI). The tumor microenvironment (TME) plays a substantial role in therapeutic resistance by facilitating immune evasion. An extracellular stromal protein, βig-h3/TGFβi, is involved in the pathogenesis of PDAC by hampering T cell activation and promoting stiffness of the TME. The study BIGHPANC included 41 patients with metastatic PDAC, and analyzed βig-h3 levels in serum and tumor samples to assess the βig-h3 prognostic value. βig-h3 serum levels are significantly associated with overall survival (HR 2.05, 95%CI 1.07-3.93; p = 0.0301). Our results suggest that βig-h3 serum levels may be considered a prognostic biomarker in patients with metastatic PDAC.
Insights
Pancreatic cancer (PDAC) has poor survival rates. Researchers found that higher levels of the protein βig-h3 in patient serum correlate with shorter survival, suggesting it may be a useful prognostic biomarker for metastatic PDAC.
Area of Science:
- Oncology
- Cancer Biology
- Biomarker Discovery
Background:
- Pancreatic ductal adenocarcinoma (PDAC) has a dismal 5-year survival rate (2-9%) and is projected to become the second leading cause of cancer death by 2030.
- PDAC often evades effective treatment, including immune checkpoint inhibitors (ICI), due to late diagnosis and a tumor microenvironment (TME) that promotes immune evasion.
- The protein βig-h3 (also known as TGFβi) is implicated in PDAC pathogenesis, contributing to T cell suppression and TME stiffening.
Purpose of the Study:
- To investigate the prognostic value of βig-h3 levels in patients with metastatic PDAC.
- To assess the association between serum and tumor βig-h3 levels and overall survival in PDAC patients.
Main Methods:
- The BIGHPANC study analyzed βig-h3 levels in serum and tumor samples from 41 patients with metastatic PDAC.
- Statistical analysis was performed to determine the correlation between βig-h3 levels and overall survival.
Main Results:
- Elevated serum βig-h3 levels were found to be significantly associated with reduced overall survival in metastatic PDAC patients (HR 2.05, 95%CI 1.07-3.93; p = 0.0301).
- The study identified a significant link between βig-h3 serum concentration and patient prognosis.
Conclusions:
- Serum βig-h3 levels demonstrate potential as a prognostic biomarker for patients diagnosed with metastatic PDAC.
- Further research into βig-h3's role could inform therapeutic strategies and improve patient outcomes in pancreatic cancer.
