JMIR Publications

ABSTRACT

Background:

The pro-inflammatory cytokine IL-6 is involved in the development and progression of tumorigenesis through the activation of the JAK-STAT3 cascade in pancreatic cancer. Inhibiting the IL-6/GP130/STAT3 sequence might therefore be a potential therapeutic strategy for pancreatic cancer.

Objective:

This study aims to evaluate the activation of the IL-6/GP130/STAT3 pathway on previously obtained biopsies of patients with pancreatic adenocarcinoma, expressed as percentage in stroma and tumor. Furthermore, it evaluates the association of the pathway activation with tumour stage, survival, and metabolic parameters including the need for oral antidiabetic medication, insulin therapy, and HbA1c levels.

Methods:

This is a retrospective, cross-sectional study on patients with pancreatic adenocarcinoma that were treated at the Hospital of Fribourg, Switzerland, between 2010 and 2024. Previously taken pathology samples will be stained using immunohistochemistry for the IL-6 /GP130/STAT3 pathway activation. To calculate the sample size, we assume that patients with strong IL-6 pathway activation have a worse prognosis than those with less activation. If we assume further a difference of 5% in activation, 84 patients in each group would correspond to 90% power, and 104 patients each to 95% power. Regarding our second primary outcome, the relationship between IL-6 activation and diabetes, we will analyse Diabetes as a dichotomous variable and the activation of the STAT3/IL6 pathway as a continuous variable. Percentages of IL-6 pathway activation and measured clinical features will be reported. Means of values (pathway activation, laboratory values) will be compared. Survival differences between patients with strong versus weak pathway activation will be compared in a Cox hazard analysis. Hazard ratios (between patients with weak and strong pathway activation) will be calculated for all examined metabolic parameters (need for oral antidiabetic medication, insulin therapy, HbA1c) to explore a possible association between pathway activation and diabetes. A 95% confidence interval will be reported. Numbers of cases with missing data for all analyses will be reported.

Results:

The study is funded by a Research Grant of HFR (Hospital Freiburg/Fribourg, 2/2021). Ethics approval of the Ethics Committee Bern, Switzerland, was granted in 10/2024 (Project-ID 2024-01215). We have identified 175 patients with remaining tissue samples in our database. On 22.04.2025 80 samples have been stained for pathway activation and 63 patient records have been added to RedCap.

Conclusions:

The strength of our study protocol is that it will be one of the first translational studies on the IL-6/STAT3 pathway in pancreatic cancer. We will be able to show association of this pathway with clinical parameters in pancreatic cancer patients. This might lead to further research in targeted therapies, taking disease phenotype into account.