Abstract C030: Serum levels and tumor tissue organization of decorin in pancreatic cancer: Links to chemoresistance and disease aggressiveness

Abstract

Abstract Pancreatic cancer has nearly paralleling incidence and mortality rates. Only 15-20% of the tumors are resectable at presentation, and for the majority of patients the situation is palliative. Treatment options are limited to standard chemotherapy, and tumor response is often transient. The longitudinal observational clinical study Chemotherapy, Host response And Molecular dynamics in Periampullary cancer (CHAMP) aims to contribute with new insights on this devastating disease through longitudinal blood sampling during adjuvant and palliative chemotherapy and comprehensive analysis of tissue from resected as well as postmortem sampled tumor tissue. In the present study, encompassing the first 100 patients enrolled in the CHAMP study, 92 serum proteins related to inflammation and cancer were analyzed by proximity extension assay in on-treatment blood samples from baseline to six months. The results revealed that the small leucin-rich proteoglycan decorin was among the top up-regulated proteins during chemotherapy. After three months of treatment, high levels of serum decorin were significantly associated with a shorter overall survival (log rank p = 0.005). Decorin expression was also assessed by immunohistochemistry in resected tumors from 25 patients and in postmortem sampled primary tumors and metastases from 9 patients. In the latter, particularly strong expression of decorin, both in the tumor cells and in the stroma, was denoted in cases with a short overall survival. While there was no significant correlation between decorin in the tumors and in serum at baseline, strong correlations were seen at one and three months (Spearman’s rho = 0.70 and 0.85, respectively). To further validate the potential prognostic value of decorin, immunohistochemical analysis was performed on tumors from a retrospective cohort of 104 resected tumors with long-term follow-up. Survival analysis showed that high decorin expression in both the stromal compartment and in tumor cells was associated with shorter overall survival (log rank p = 0.036 and 0.001, respectively). Multivariable cox regression analysis, adjusted for conventional prognostic factors, further confirmed that decorin was an independent factor of shorter overall survival (hazard ratio: 1.74, 95% confidence interval 1.10-2.75 for stromal decorin, and hazard ratio: 1.83, 95% confidence interval 1.04-3.21 for tumor-cell specific decorin). In conclusion, these findings suggest that decorin may be associated with chemotherapy resistance in pancreatic cancer. Future studies are encouraged to further explore the mechanistic basis for these observations, and to validate the potential utility of serum-decorin as a biomarker to monitor treatment response. Citation Format: Maja Svensson, Johan Ohlsson, Sofie Olsson Hau, Alexandra Petersson, Karin Jirström. Serum levels and tumor tissue organization of decorin in pancreatic cancer: Links to chemoresistance and disease aggressiveness [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Pancreatic Cancer; 2023 Sep 27-30; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(2 Suppl):Abstract nr C030.