N-acetyltransferase 10 (NAT10) is a histone acetyltransferase which is involved in a wide range of cellular processes. Recent evidences indicate that NAT10 is involved in the development of human cancers. Previous study showed that NAT10 acetylates the tumor suppressor p53 and regulates p53 activation. As Tp53 gene is frequently mutated in hepatocellular carcinoma (HCC) and associates with the occurrence and development of HCC, the relationship between NAT10 and HCC was investigated in this study. Immunohistochemistry (IHC) and western blot analysis were performed to evaluate the NAT10 expression in HCC. Immunoprecipitation experiments were performed to verify the interaction of NAT10 with mutant p53 and Mdm2. RNA interference and Western blot were applied to determine the effect of NAT10 on mutant p53. Cell growth curve was used to examine the effect of NAT10 on HCC cell proliferation. NAT10 was upregulated in HCC and increased NAT10 expression was correlated with poor overall survival of the patients. NAT10 protein levels were significantly correlated with p53 levels in human HCC tissues. Furthermore, NAT10 increased mutant p53 levels by counteracting Mdm2 action in HCC cells and promoted proliferation in cells carrying p53 mutation. Increased NAT10 expression levels are associated with shortened patient survival and correlated with mutant p53 levels. NAT10 upregulates mutant p53 level and might enhance its tumorigenic activity. Hence, we propose that NAT10 is a potential prognostic and therapeutic candidate for p53-mutated HCC.

Purpose: The incidence of early-onset CRC is increasing. However, the effect of age of onset on the long-term outcome of colorectal cancer liver metastasis (CRLM) remains unclear. This study aimed to evaluate the association between the age of onset and the oncological outcome of CRLM patients and to investigate whether the prognostic role of RAS mutation is altered with age. Methods: We retrospectively investigated consecutive patients at our institution who underwent initial liver resection between 2006 and 2020. The inverse probability of treatment weighting (IPTW) method was used to balance the confounders among early- (≤45 years; EOCRLM), intermediate- (46–70 years; IOCRLM), and late-onset (>70 years; LOCRLM) groups. The prognostic role of RAS was assessed based on age group. Results: A total of 1189 patients were enrolled: 162 in the EOCRLM group, 930 in the IOCRLM group, and 97 in the LOCRLM group. No difference in disease-free survival (DFS) was found between the three groups. However, EOCRLM were more likely to develop extrahepatic and extrapulmonary metastasis and had significantly lower five-year OS rates than IOCRLM. After IPTW, EOCRLM remained a negative prognostic predictor. RAS mutations were significantly associated with worse survival than wild-type RAS in EOCRLM and IOCRLM. However, RAS mutation did not predict the prognosis of patients with LOCRLM. Conclusions: Patients with EOCRLM had a significantly lower OS than IOCRLM patients and age influences the prognostic power of RAS status. These findings may be helpful for doctors to guide the clinical treatments and develop follow-up strategies.