In:
Journal of Gastroenterology, Springer Science and Business Media LLC, Vol. 58, No. 10 ( 2023-10), p. 1055-1067
Kurzfassung:
Abundant collagen deposition is a hallmark of pancreatic ductal adenocarcinomas (PDACs). This study clarified the interactive relationship between tumor-stromal collagen, molecular and immune characteristics, and tumor pr ogression in human PDAC. Methods We performed a comprehensive examination using an integrative molecular pathological epidemiology database on 169 cases with resected PDAC . The amount of tumor-stromal collagen was quantified through digital imaging analysis for Elastica van Gieson-stained whole-section tumor slides. We analyzed the association of tumor-stromal collagen with gene alterations ( KRAS , TP53 , CDKN2A /p16, and SMAD4 ), immune parameters (CD4 + tumor-infiltrating lymphocytes [TILs], CD8 + TILs, FOXP3 + TILs, and tertiary lymphoid structures), and patient prognosis. Results Low amounts of tumor-stromal collagen were associated with poor differentiation (multivariable OR = 3.82, 95%CI = 1.41–12.2, P = 0.008) and CDKN2A /p16 alteration (OR [95%CI] = 2.06 [1.08–4.02] , P = 0.03). Tumors with low collagen levels had shorter overall survival (HR [95%CI] = 2.38 [1.59–3.56], P 〈 0.0001). In the S-1 and gemcitabine (GEM) treatment groups, low tumor-stromal collagen was linked to poor prognosis of patients with PDAC (S-1 group: multivariable HR [95%CI] = 2.76 [1.36–5.79] , P = 0.005; GEM group: multivariate HR [95%CI] = 2.91 [1.34–6.71] , P = 0.007). Additionally, low amounts of tumor-stromal collagen were also linked to low levels of CD4 + TILs ( P = 0.046), CD8 + TILs ( P = 0.09), and tertiary lymphoid structures ( P = 0.001). Conclusions Tumor-stromal collagen deposition may play a crucial role in modulating tumor-immune microenvironment and determining response to adjuvant chemotherapy and patient survival outcomes.
Materialart:
Online-Ressource
ISSN:
0944-1174
,
1435-5922
DOI:
10.1007/s00535-023-02020-8
Sprache:
Englisch
Verlag:
Springer Science and Business Media LLC
Publikationsdatum:
2023
ZDB Id:
1473159-9
