Abstract
BackgroundWNT/βcatenin (WNTβ) pathway is activated in early stages of embryonic development. We aimed to evaluate the significance of βcatenin in germ cell tumors (GCTs) and explore associations with the inflamed environment.MethodsSurgical specimens from 247 patients were analyzed. Βcatenin expression was detected in the tumor tissue by immunohistochemistry and correlated with clinical characteristics, outcome, PD-L1 expression and systemic immune-inflammation index (SII). The Ingenuity Pathway Analysis (IPA) was used to investigate the immune-cell related effects of βcatenin and PD-L1 encoding genes.Resultsβcatenin was expressed in 86.2% of GCTs. The expression in seminomas was significantly lower compared to all subtypes of non-seminoma (all P < 0.0001). A high expression (weighted histoscore > 150) was associated with primary mediastinal non-seminoma (P = 0.035), intermediate/poor risk disease (P = 0.033) and high tumor markers (P = 0.035). We observed a positive correlation with the PD-L1 in tumor and an inverse correlation with the SII. IPA uncovered relationships of CTNNB (βcatenin) and CD274 (PD-L1) genes and their effects on differentiation, proliferation and activation of lymphocyte subtypes.ConclusionHerein, we showed that βcatenin is associated with male adult GCT characteristics as well as supressed immune environment.
Highlights
WNT/βcatenin (WNTβ) pathway is activated in early stages of embryonic development
We aimed to evaluate the role of βcatenin in Germ cell tumor (GCT) and find correlations with systemic immune-inflammation and PD-L1 expression in tumor and tumor infiltrating lymphocytes (TILs)
Tumor specimens from 247 patients before administration of systemic therapy included 50 pure seminomas, 128 non-seminomas (86 embryonal carcinomas, 19 yolk sac tumors, 1 choriocarcinoma, 22 teratomas) and 69 mixed GCTs. (Additional file 1: Table S1)
Summary
We aimed to evaluate the significance of βcatenin in germ cell tumors (GCTs) and explore associations with the inflamed environment. Testicular-germ cell tumors (GCTs) are chemotherapy sensitive malignancies [1, 2]. The significance of PD-1/PD-L1 pathway as well as the role of systemic-immune inflammation was previously described in our works [3, 4]. The role of βcatenin and WNTB signalling and its clinical implications in GCTs have not been comprehensively explored. In this retrospective study, we aimed to evaluate the role of βcatenin in GCTs and find correlations with systemic immune-inflammation and PD-L1 expression in tumor and tumor infiltrating lymphocytes (TILs)
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