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RESEARCH PRODUCT

Stromal hyaluronan accumulation is associated with low immune response and poor prognosis in pancreatic cancer

Raija TammiMaarit AhtiainenKyösti TahkolaJukka-pekka MecklinJan BöhmIlmo KellokumpuJuha P. VäyrynenJohanna LaukkarinenMarkku Tammi

subject

0301 basic medicineMalehyaluronaanibiomarkkeritB7-H1 Antigen0302 clinical medicineProspective StudiesHyaluronic Acid5'-NucleotidasehaimasyöpäCancerAged 80 and overMultidisciplinaryQGastroenterologyRMiddle AgedPrognosisSurvival RateOncology030220 oncology & carcinogenesisimmuunivasteImmunohistochemistryMedicineFemalesyöpätauditCarcinoma Pancreatic DuctalStromal cellScienceImmunologyGPI-Linked Proteins3121 Internal medicineArticle03 medical and health sciencesImmune systemPancreatic cancerCarcinomamedicineHumansSurvival rateAgedbusiness.industryImmunityCancerennusteetmedicine.disease3126 Surgery anesthesiology intensive care radiologyPancreatic Neoplasms030104 developmental biologyCancer researchStromal CellsbusinessCD8Follow-Up Studies

description

AbstractHyaluronan (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.

10.1038/s41598-021-91796-xhttps://trepo.tuni.fi/handle/10024/133203