2529 - A protein level signature of four selected genes associated with survival outcomes of patients with pancreatic ductal adenocarcinoma

Background

Compared with quantification of messenger RNA, a protein level quantification allows for more relevant clinical outcome predictions and the identification of potential therapeutic targets. The aim of this study was to identify a novel protein level signature that was associated with overall survival in patients with resected pancreatic ductal adenocarcinoma (PDAC).

Methods

Data of 105 patients with resected PDAC were retrieved from TRGAted. Reverse-phase protein array (RPPA) quantification data of 218 proteins were collected. By using the LASSO regression model, a protein-level-based classifier was built. Time-dependent receiver operating characteristic (ROC) analysis was used to assess the prognostic accuracy of the classifier. Survival curves were compared by using the Kaplan-Meier analysis.

Results

Using the LASSO model, we built a classifier based on four proteins: BAK, IGFBP2, PDL1, and BRAF-pS445. Survival analysis revealed IGFBP2 and BRAF-pS445 were two favourable prognostic markers, and BAK and PDL1 were unfavourable prognostic markers. Using the classifier, we were able to classify patients between those at high risk of disease progression (high-risk group) and those at low risk of disease progression (low-risk group). Progression-free survival was significantly different between these two groups (11.7 vs 19.9 months for high-risk and low-risk groups, respectively; P < 0.0001). The median overall survival was 13.1 and 36.7 months for the high-risk and low-risk groups, respectively (hazard ratio [HR]: 4.09; 95% CI: 2.39 - 6.98; P < 0.0001). Five-year survival rate was 0% for the high-risk group, and 46% for the low-risk group. The prognostic accuracy (area under the ROC curve) of the classifier were 0.75, 0.77, and 0.81 at 1, 3, and 5 years, respectively. Multivariate Cox regression analysis showed that the classifier was an independent prognostic factor (P < 0.0001).

Conclusions

This protein-level classifier is a novel prognostic tool in patients with resected PDAC. It may facilitate individualized management of patients with this disease.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Jie Hua.

Funding

The National Science Fund for Distinguished Young Scholars of China (grant number 81625016).

Disclosure

All authors have declared no conflicts of interest.