Abstract
Hyaluronan (HA) accumulation has been associated with poor survival in various cancers, but the mechanisms for this phenomenon are still unclear. The aim of this study was to investigate the prognostic significance of stromal HA accumulation and its association with host immune response in pancreatic ductal adenocarcinoma (PDAC). The study material consisted of 101 radically treated patients for PDAC from a single geographical area. HA staining was evaluated using a HA-specific probe, and the patterns of CD3, CD8, CD73 and PD-L1 expression were evaluated using immunohistochemistry. HA staining intensity of tumour stromal areas was assessed digitally using QuPath. CD3- and CD8-based immune cell score (ICS) was determined. High-level stromal HA expression was significantly associated with poor disease-specific survival (p = 0.037) and overall survival (p = 0.013) In multivariate analysis, high-level stromal HA expression was an independent negative prognostic factor together with histopathological grade, TNM stage, CD73 positivity in tumour cells and low ICS. Moreover, high-level stromal HA expression was associated with low ICS (p = 0.017). In conclusion, stromal HA accumulation is associated with poor survival and low immune response in PDAC.
Highlights
Hyaluronan (HA) accumulation has been associated with poor survival in various cancers, but the mechanisms for this phenomenon are still unclear
Stromal HA accumulation appeared to associate with low immune cell score (ICS) (p = 0.017)
In the present study, using a larger, consecutive patient series from a single geographical area of Northern Finland without apparent selection bias, we showed the role of stromal HA accumulation as an independent prognostic factor for poor survival in pancreatic cancer
Summary
Hyaluronan (HA) accumulation has been associated with poor survival in various cancers, but the mechanisms for this phenomenon are still unclear. The aim of this study was to investigate the prognostic significance of stromal HA accumulation and its association with host immune response in pancreatic ductal adenocarcinoma (PDAC). High-level stromal HA expression was significantly associated with poor disease-specific survival (p = 0.037) and overall survival (p = 0.013) In multivariate analysis, high-level stromal HA expression was an independent negative prognostic factor together with histopathological grade, TNM stage, CD73 positivity in tumour cells and low ICS. Stromal HA accumulation is associated with poor survival and low immune response in PDAC. Abbreviations HA Hyaluronan ICS Immune cell score PDAC Pancreatic ductal adenocarcinoma DSS Disease-specific survival OS Overall survival TMA Tissue microarray. Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive solid malignancies with 5-year survival rates of 2–9%1,2 This is partly related to advanced disease stage at the time of diagnosis ruling out curative surgery. Medicine Research Unit, Medical Research Center Oulu, University of Oulu and Oulu University Hospital, Oulu, Scientific Reports | (2021) 11:12216
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