Jing Jin1, Hae Yoen Jung1, Yuli Wang2, Julie Xie2, Yong Il Yeom3, Ja-June Jang4, Kyong Bun Lee5. 1. Department of Pathology, Seoul National University College of Medicine, 28 Yongon-dong, Chongno-gu, Seoul 110-799, Republic of Korea. 2. Pfizer Global Research and Development, 10770 Science Center Drive, San Diego, CA 92121, USA. 3. Korea Research Institute of Bioscience & Biotechnology, 125 Gwahangno, Daejeon 304-806, Republic of Korea. 4. Department of Pathology, Seoul National University College of Medicine, 28 Yongon-dong, Chongno-gu, Seoul 110-799, Republic of Korea; Department of Pathology, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul 110-744, Republic of Korea. 5. Department of Pathology, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul 110-744, Republic of Korea. Electronic address: azirang@chol.com.
Abstract
BACKGROUND AND AIMS: TRAF2- and NCK-interacting kinase (TNIK) is a member of the germinal center kinase family and a transcription factor 4 (TCF4) interactor is recruited to promoters of Wnt target genes via phosphorylation of the TCF/β-catenin complex. The aim of this study was to evaluate the TNIK, the active form of TNIK (p-TNIK), and β-catenin expression in hepatocellular carcinoma (HCC), and to identify the prognostic significance of p-TNIK. METHODS: We assessed the expression status of TNIK, p-TNIK, and β-catenin by using immunohistochemical analysis of 302 HCCs in 8 tissue microarray blocks, and we evaluated their clinicopathologic features and survival rates based on their p-TNIK expression. RESULTS: Of 302 HCCs, 92.7% stained positive for TNIK in the cytoplasm. Nuclear expression of p-TNIK was identified in 7.9% HCCs. Aberrant cytoplasmic expression of β-catenin was identified in 77.2% and nuclear expression in 3.3%. p-TNIK nuclear staining was positively correlated to β-catenin nuclear expression (P=0.036). Cytoplasmic and nuclear expression of p-TNIK was more frequently observed in high Edmondson-Steiner (ES) nuclear grade groups (P=0.030). Nuclear p-TNIK expression was also associated with pathological M1 stage (pM1 stage) patients (P<0.0001). Aberrant cytoplasmic expression of β-catenin was more frequently identified in larger tumors (P=0.014). Univariate (DFS, P=0.049; OS, 0.037) and multivariate analysis (DFS, P=0.006; OS, P=0.003) confirmed the independent prognostic significance of nuclear p-TNIK expression. CONCLUSION: This is the first time that nuclear p-TNIK expression was studied in HCC, and p-TNIK nuclear expression was associated with poor prognosis and is a candidate prognostic marker for HCC.
BACKGROUND AND AIMS: TRAF2- and NCK-interacting kinase (TNIK) is a member of the germinal center kinase family and a transcription factor 4 (TCF4) interactor is recruited to promoters of Wnt target genes via phosphorylation of the TCF/β-catenin complex. The aim of this study was to evaluate the TNIK, the active form of TNIK (p-TNIK), and β-catenin expression in hepatocellular carcinoma (HCC), and to identify the prognostic significance of p-TNIK. METHODS: We assessed the expression status of TNIK, p-TNIK, and β-catenin by using immunohistochemical analysis of 302 HCCs in 8 tissue microarray blocks, and we evaluated their clinicopathologic features and survival rates based on their p-TNIK expression. RESULTS: Of 302 HCCs, 92.7% stained positive for TNIK in the cytoplasm. Nuclear expression of p-TNIK was identified in 7.9% HCCs. Aberrant cytoplasmic expression of β-catenin was identified in 77.2% and nuclear expression in 3.3%. p-TNIK nuclear staining was positively correlated to β-catenin nuclear expression (P=0.036). Cytoplasmic and nuclear expression of p-TNIK was more frequently observed in high Edmondson-Steiner (ES) nuclear grade groups (P=0.030). Nuclear p-TNIK expression was also associated with pathological M1 stage (pM1 stage) patients (P<0.0001). Aberrant cytoplasmic expression of β-catenin was more frequently identified in larger tumors (P=0.014). Univariate (DFS, P=0.049; OS, 0.037) and multivariate analysis (DFS, P=0.006; OS, P=0.003) confirmed the independent prognostic significance of nuclear p-TNIK expression. CONCLUSION: This is the first time that nuclear p-TNIK expression was studied in HCC, and p-TNIK nuclear expression was associated with poor prognosis and is a candidate prognostic marker for HCC.
Authors: Liang-Hao Ding; Yongjia Yu; Elijah F Edmondson; Michael M Weil; Laurentiu M Pop; Maureen McCarthy; Robert L Ullrich; Michael D Story Journal: Sci Rep Date: 2021-07-07 Impact factor: 4.379