A comprehensive analysis of tumor-stromal collagen in relation to pathological, molecular, and immune characteristics and patient survival in pancreatic ductal adenocarcinoma

Background 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