Early recurrence (within 2 years after resection) is the primary cause of poor outcomes among hepatocellular carcinoma (HCC) patients, and liver cancer stem cells are the main contributors to postsurgical HCC recurrence. Nucleolar and spindle‐associated protein 1 (NUSAP1) has been reported to be involved in tumor progression. We investigated the function and clinical value of NUSAP1 in early recurrence of HCC. Data from public datasets and our cohort were used to assess the association between NUSAP1 expression and early HCC recurrence. Gain‐ and loss‐of‐function experiments were carried out in vivo and in vitro. The predictive effect of NUSAP1 on early HCC recurrence was further evaluated by a validation cohort. We found that elevated NUSAP1 expression in HCC specimens was correlated with poor outcome, especially in cases with postoperative early recurrence. Functional studies indicated that NUSAP1 significantly promotes HCC progression. A postsurgical recurrence murine model further revealed that upregulated NUSAP1 dramatically increased the likelihood of HCC early recurrence. RNA sequencing data revealed that the gene sets of cancer stemness and the signal transducer and activator of transcription 3 (STAT3) pathway were enriched by NUSAP1 overexpression. Mechanistically, NUSAP1 enhanced cancer stemness through stimulating STAT3 nuclear translocation and activation through receptor of activated protein C kinase 1 (RACK1). In a validation cohort with 112 HCC patients, NUSAP1 effectively predicted HCC early recurrence. Our results indicated that NUSAP1 promotes early recurrence of HCC by sustaining cancer stemness and could serve as a valuable predictive indicator for postsurgical intervention in HCC patients.

Background:Pancreatic ductal adenocarcinoma (PDAC) accounts for 85% of pancreatic carcinoma cases. Patients with PDAC have a poor prognosis. The lack of reliable prognostic biomarkers makes treatment challenging for patients with PDAC. Using a bioinformatics database, we sought to identify prognostic biomarkers for PDAC. Material/Methods:Using proteomic analysis of the Clinical Proteomics Tumor Analysis Consortium (CPTAC) database, we were able to identify core differential proteins between early and advanced pancreatic ductal adenocarcinoma tissue, and then we used survival analysis, Cox regression analysis, and area under the ROC curves to screen for more significant differential proteins. Additionally, the Kaplan-Meier plotter database was utilized to determine the relationship between prognosis and immune infiltration in PDAC. Results:We identified 378 differential proteins in early (n=78) and advanced stages (n=47) of PDAC (P<0.05). PLG, COPS5, FYN, ITGB3, IRF3, and SPTA1 served as independent prognostic factors of patients with PDAC. Patients with higher COPS5 expression had shorter overall survival (OS) and recurrence-free survival, and those with higher PLG, ITGB3, and SPTA1, and lower FYN and IRF3 expression had shorter OS. More importantly, COPS5, IRF3 were negatively associated with macrophages and NK cells, but PLG, FYN, ITGB3, and SPTA1 were positively related to the expression of CD8+ T cells and B cells. COPS5 affected the prognosis of PDAC patients by acting on B cells, CD8+ T cells, macrophages, and NK cells immune infiltration, while PLG, FYN, ITGB3, IRF3, and SPTA1 affected PDAC patient prognosis through some immune cells. Conclusions:PLG, COPS5, FYN, IRF3, ITGB3 and SPTA1 could be potential immunotherapeutic targets and valuable prognostic biomarkers of PDAC.