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000181146 041__ $$aEnglish
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000181146 1001_ $$aAmbrozkiewicz, Filip$$b0
000181146 245__ $$aCTNNB1 mutations, TERT polymorphism and CD8+ cell densities in resected hepatocellular carcinoma are associated with longer time to recurrence.
000181146 260__ $$aHeidelberg$$bSpringer$$c2022
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000181146 520__ $$aHepatocellular carcinoma (HCC) is a fatal disease characterized by early genetic alterations in telomerase reverse transcriptase promoter (TERTp) and β-catenin (CTNNB1) genes and immune cell activation in the tumor microenvironment. As a novel approach, we wanted to assess patient survival influenced by combined presence of mutations and densities of CD8+ cytotoxic T cells.Tissue samples were obtained from 67 HCC patients who had undergone resection. We analysed CD8+ T cells density, TERTp mutations, rs2853669 polymorphism, and CTNNB1 mutations. These variables were evaluated for time to recurrence (TTR) and disease free survival (DFS).TERTp mutations were found in 75.8% and CTNNB1 mutations in 35.6% of the patients. TERTp mutations were not associated with survival but polymorphism rs2853669 in TERTp was associated with improved TTR and DFS. CTNNB1 mutations were associated with improving TTR. High density of CD8+ T-lymphocytes in tumor center and invasive margin correlated with longer TTR and DFS. Combined genetic and immune factors further improved survival showing higher predictive values. E.g., combining CTNNB1 mutations and high density of CD8+ T-lymphocytes in tumor center yielded HRs of 0.12 (0.03-0.52), p = 0.005 for TTR and 0.25 (0.09-0.74), p = 0.01 for DFS.The results outline a novel integrative approach for prognostication through combining independent predictive factors from genetic and immune cell profiles. However, larger studies are needed to explore multiple cell types in the tumor microenvironment.
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000181146 650_7 $$2Other$$aCD8+ cells
000181146 650_7 $$2Other$$aHepatocellular carcinoma
000181146 650_7 $$2Other$$aTERT promoter
000181146 650_7 $$2Other$$ars2853669
000181146 650_7 $$2Other$$aβ-Catenin
000181146 7001_ $$aTrailin, Andriy$$b1
000181146 7001_ $$aČervenková, Lenka$$b2
000181146 7001_ $$aVaclavikova, Radka$$b3
000181146 7001_ $$aHanicinec, Vojtech$$b4
000181146 7001_ $$aAllah, Mohammad Al Obeed$$b5
000181146 7001_ $$aPalek, Richard$$b6
000181146 7001_ $$aTřeška, Vladislav$$b7
000181146 7001_ $$aDaum, Ondrej$$b8
000181146 7001_ $$aTonar, Zbyněk$$b9
000181146 7001_ $$aLiška, Václav$$b10
000181146 7001_ $$0P:(DE-He78)19b0ec1cea271419d9fa8680e6ed6865$$aHemminki, Kari$$b11$$eLast author$$udkfz
000181146 773__ $$0PERI:(DE-600)2041352-X$$a10.1186/s12885-022-09989-0$$gVol. 22, no. 1, p. 884$$n1$$p884$$tBMC cancer$$v22$$x1471-2407$$y2022
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