Background: Hepatocellular carcinoma (HCC) is a common malignancy with high mortality worldwide. Despite advancements in diagnosis and treatment in recent years, there is still an urgent unmet need to explore the underlying mechanisms and novel prognostic markers. Anoikis has received considerable attention because of its involvement in the progression of human malignancies. However, the potential mechanism of anoikis-related genes (ANRGs) involvement in HCC progression remains unclear.Methods: We use comprehensive bioinformatics analyses to determine the expression profile of ANRGs and their prognostic implications in HCC. Next, a risk score model was established by least absolute shrinkage and selection operator (Lasso) Cox regression analysis. Then, the prognostic value of the risk score in HCC and its correlation with clinical characteristics of HCC patients were further explored. Additionally, machine learning was utilized to identify the outstanding ANRGs to the risk score. Finally, the protein expression of DAP3 was examined on a tissue microarray (TMA), and the potential mechanisms of DAP3 in HCC was explored.Results: ANRGs were dysregulated in HCC, with a low frequency of somatic mutations and associated with prognosis of HCC patients. Then, nine ANRGs were selected to construct a risk score signature based on the LASSO model. The signature presented a strong ability of risk stratification and prediction for overall survival in HCC patients.Additionally, high risk scores were closely correlated with unfavorable clinical features such as advanced pathological stage, poor histological differentiation and vascular invasion. Moreover, The XGBoost algorithm verified that DAP3 was an important risk score contributor. Further immunohistochemistry determined the elevated expression of DAP3 in HCC tissues compared with nontumor tissues. Finally, functional analyses showed that DAP3 may promote HCC progression through multiple cancer-related pathways and suppress immune infiltration.Conclusion: In conclusion, the anoikis-based signature can be utilized as a novel prognostic biomarker for HCC, and DAP3 may play an important role in the development and progression of HCC.

Purpose Hepatocellular carcinoma (HCC) has high morbidity and poor prognosis due to the propensity of recurrence and metastasis. Emerging studies have confirmed that proline-rich coiled-coil2A (PRRC2A) plays a crucial role in tumorigenesis and immunoregulation. However, its expression status and biological functions in HCC remain poorly documented. Methods The presence and prognostic value of PRRC2A were determined by a tissue microarray (TMA) cohort and multiple databases, mainly from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), Clinical Proteomic Tumor Analysis Consortium (CPTAC). Functional enrichment analysis was applied to identify the mechanisms of PRRC2A in HCC. The biological function of PRRC2A in HCC progression in vitro was determined by CCK-8, colony formation, EdU, transwell migration and invasion assays. Moreover, the Estimation of STromal and Immune cells in Malignant Tumor tissues using Expression data (ESTIMATE), single-sample gene set enrichment analysis (ssGSEA), tumor immune dysfunction and exclusion (TIDE) algorithms, immunophenoscore (IPS) and public available immunotherapy cohorts were performed to classify their associations with tumor-infiltrating immune cells and immunotherapy. Results PRRC2A was upregulated in HCC at both mRNA and protein levels. High PRRC2A expression was correlated with poor prognosis and could be an independent risk factor. Functional enrichment analysis demonstrated that elevated PRRC2A was significantly correlated with the activation of various oncogenic pathways. Additionally, in vitro experiments confirmed that silencing PRRC2A could suppress the proliferation and metastasis capacities of HCC cells. More importantly, PRRC2A was negatively associated with many anti-tumor immune cells, but positively related to the expression of markers of exhaustive T cells. And HCC patients with high PRRC2A were more likely to be nonresponsive to immunotherapy. Conclusion This study explored the predictive value and biological roles of PRRC2A in HCC progression and indicated that it might be a potential biomarker for HCC patients and a predictor for immunotherapy.

NSUN2 is a nuclear RNA methyltransferase which catalyzes 5-methylcytosine (m5C), a posttranscriptional RNA modification. Aberrant m5C modification has been implicated in the development of multiple malignancies. However, its function in pancreatic cancer (PC) needs to be elucidated. Herein, we determined that NSUN2 was overexpressed in PC tissues and related to aggressive clinical features. Silence of NSUN2 by lentivirus weakened the capability of proliferation, migration and invasion of PC cells in vitro and inhibited the growth and metastasis of xenograft tumors in vivo. Contrarily, overexpression of NSUN2 stimulated PC growth and metastasis. Mechanistically, m5C-sequencing (m5C-seq) and RNA-sequencing (RNA-seq) were carried out to identify downstream targets of NSUN2 and results showed that loss of NSUN2 led to decreased m5C modification level concomitant with reduced TIAM2 mRNA expression. Further validation experiments proved that NSUN2 silence accelerated the decay of TIAM2 mRNA in a YBX1-dependent manner. Additionally, NSUN2 exerted its oncogenic function partially through enhancing TIAM2 transcription. More importantly, disruption of the NSUN2/TIAM2 axis repressed the malignant phenotype of PC cells through blocking epithelial-mesenchymal transition (EMT). Collectively, our study highlighted the critical function of NSUN2 in PC and provided novel mechanistic insights into NSUN2/TIAM2 axis as promising therapeutic targets against PC.