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Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

14-3-3 proteins are ubiquitous adapters combining with phosphorylated serine/threonine motifs to regulate multiple cellular processes. As a negative regulator, 14-3-3 proteins could sequester the phosphorylated YAP1 in cytoplasm to inhibit its activity. In this study, we identified the K50 acetylation (K50ac) of 14-3-3ε protein and investigated its roles and mechanism in cholangiocarcinoma progression. The NAD (+)-dependent protein deacetylases inhibitor, NAM treatment significantly up-regulated the K50ac of 14-3-3ε. K50R mutation resulted in the decrease of K50ac of 14-3-3ε. The K50ac of 14-3-3ε was reversibly mediated by PCAF acetyltransferase and sirt1 deacetylases. K50ac had no obvious effect on the protein stability of 14-3-3ε, but inhibited the combination of 14-3-3ε with phosphorylated YAP1, which resulted in the activation of YAP1 in cholangiocarcinoma. K50R significantly decreased cholangiocarcinoma cell proliferation in vitro and the growth of tumor xenograft in vivo compared with WT (wild type) 14-3-3ε. The level of K50ac were higher in cholangiocarcinoma tissues accompanied by the accumulation of YAP1 in nuclear than para-carcinoma tissues. Our study revealed the underlying mechanism of K50ac of 14-3-3ε and its roles in cholangiocarcinoma, providing a potential targeting for cholangiocarcinoma therapy., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Purpose: 18F-FDG PET/MR has been applied to the diagnosis and preoperative staging in various tumor types; however, reports using PET/MR in hilar cholangiocarcinoma (HCCA) are rare. We investigated the value of PET/MR for preoperative staging and compared it with PET/CT in HCCA. Methods: Fifty-eight patients with HCCA confirmed by pathology were retrospectively analyzed. 18F-FDG PET/CT imaging was performed first, followed with whole-body PET/MR imaging. SUVmax of tumor and normal liver tissue were measured. Paired T test was used to compare SUVmax of tumor and normal liver tissue of PET/CT and PET/MR. In addition, McNemar test was used to compare the accuracy of TNM staging and Bismuth-Corlette typing between PET/CT and PET/MR. Results: There was no significant difference in SUVmax between PET/CT and PET/MR in primary tumor lesions (6.6 ± 5.5 vs. 6.8 ± 6.2, P = 0.439). SUVmax of PET/CT and PET/MR in normal liver parenchyma was significantly different (3.0 ± 0.5 vs. 2.1 ± 0.5, P < 0.001). The accuracy of PET/MR in diagnosing T staging and N staging was significantly higher than those of PET/CT (72.4% vs. 58.6%, P = 0.022 and 84.5% vs. 67.2%, P = 0.002). There was no significant difference between PET/CT and PET/MR in M staging (94.8% vs. 98.3%, P = 0.5). The classification accuracy of PET/MR in Bismuth-Corlette was significantly higher than that of PET/CT (89.7% vs. 79.3%), P = 0.031. Conclusions: The diagnostic accuracy of 18F-FDG PET/MR was superior to that of PET/CT in preoperative T staging, N staging, and Bismuth–Corlette classification of HCCA. In M staging, the diagnostic accuracy of PET/MR was similar to that of PET/CT. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to evaluate the role of dual-time point 18F-FDG PET/CT imaging in the primary diagnosis and staging of hilar cholangiocarcinoma (HCCA). Methods: Dual-time point FDG PET/CT findings, including early phase whole-body scanning and abdominal delayed phased performed 1 and 2 h after radiotracer injection, respectively, were retrospective reviewed in 69 patients conformed HCCA by histology. PET/CT was evaluated based on visual interpretation and the semiquantitative index of SUVmax and tumor-to-normal liver tissue ratio (TNR) for both early and delayed images. Results: For all 69 HCCA patients, the mean SUVmax of the lesion and TNR in delayed phase was significantly higher than that in early phase (6.1 ± 4.7, 2.2 ± 1.7, vs 5.1 ± 3.4, 1.6 ± 1.1; P < 0.001). The sensitivity and accuracy value of detection primary lesions was 69.6% and 70% in early phase vs 76.8% and 76.8% in delay phase, respectively. There was a significant correlation between lesion SUVmax and Ki67 index in both dual-time imaging (r = 0.462, P < 0.001 in early phase vs r = 0.47, P < 0.001 in delay phase). The sensitivity, specificity and accuracy value of metastatic lymph nodes prediction was 50%, 67.3% and 71% in early phase vs 62.5%, 73.3% and 76.8% in delayed phase, respectively. The sensitivity, specificity and accuracy of FDG PET/CT in detecting distant metastasis in our study was 75%, 100% and 97.1%. There was no difference of predicting distant metastasis between early phase and delayed phase. Conclusion: Delayed phase in dual-time point 18F-FDG PET/CT scan provides additional usefulness for detection primary tumor and lymph nodes metastases in HCCA, but there was no added benefit of delayed PET/CT imaging in detection of distant metastases in this study. SUVmax in early and delayed phase could be used to assess tumor aggressiveness in pre-treatment HCCA. [ABSTRACT FROM AUTHOR]