Background: Hepatocellular carcinoma (HCC) is a primary liver cancer with a high mortality rate. However, the molecular mechanism of HCC formation remains to be explored and studied. Objective: To investigate the expression of TOP2A in hepatocellular carcinoma (HCC) and its prognosis. Methods: The data set of hepatocellular carcinoma was downloaded from GEO database for differential gene analysis, and hub gene was identified by Cytoscape. GEPIA was used to verify the expression of HUB gene and evaluate its prognostic value. Then TOP2A was selected as the research object of this paper by combining literature and clinical sample results. Firstly, TIMER database was used to study TOP2A, and the differential expression of TOP2A gene between normal tissues and cancer tissues was analyzed, as well as the correlation between TOP2A gene expression and immune infiltration of HCC cells. Then, the expression of top2a-related antibodies was analyzed using the Human Protein Atlas database, and the differential expression of TOP2A was verified by immunohistochemistry. Then, SRTING database and Cytoscape were used to establish PPI network for TOP2A and protein–protein interaction analysis was performed. The Oncomine database and cBioPortal were used to express and identify TOP2A mutation-related analyses. The expression differences of TOP2A gene were identified by LinkedOmics, and the GO and KEGG pathways were analyzed in combination with related genes. Finally, Kaplan–Meier survival analysis was performed to analyze the clinical and prognosis of HCC patients. Results: TOP2A may be a new biomarker and therapeutic target for hepatocellular carcinoma.

Objective: This study aims to explore ADH4 expression in hepatocellular carcinoma (HCC), its prognostic impact, and its immune correlation to provide novel insights into HCC prognostication and treatment. Methods: HCC prognostic marker genes were rigorously selected using GEO database, Lasso regression, GEPIA, Kaplan-Meier and pROC analyses. The expression of interested markers (ADH4, DNASE1L3, RDH16, LCAT, HGFAC) in HCC and adjacent tissues was assessed by Immunohistochemistry (IHC). We observed that ADH4 exhibited low expression levels in liver cancer tissues and high expression levels in normal liver tissues. However, the remaining four genes did not manifest any statistically significant differences between hepatocellular carcinoma (HCC) tissue and adjacent non-cancerous tissue. Consequently, ADH4 became the primary focus of our research. ADH4 expression was validated by signed-rank tests and unpaired Wilcoxon rank sum tests across pan-cancer and HCC datasets. Clinical significance and associations with clinicopathological variables were determined using Kaplan-Meier, logistic regression and Cox analyses on TCGA data. The ADH4-related immune responses were explored by Spearman correlation analysis using TIMER2 data. CD68, CD4, and CD19 protein levels were confirmed by IHC in HCC and non-cancerous tissues. Results: ADH4 showed significant downregulation in various cancers, particularly in HCC. Moreover, low ADH4 expression was associated with clinicopathological variables and served as an independent prognostic marker for HCC patients. Additionally, ADH4 affects a variety of biochemical functions and may influence cancer development, prognosis, and treatment by binding to immune cells. Furthermore, at the immune level, the low expression pattern of ADH4 is TME-specific, indicating that ADH4 has the potential to be used as a target for cancer immunotherapy. Conclusion: This study highlights the diagnostic, prognostic and immunomodulatory roles of ADH4 in HCC. ADH4 could serve as a valuable biomarker for HCC diagnosis and prognosis, as well as a potential target for immunotherapeutic interventions.

Objective: This study aimed to investigate the role of ficolin-2 (FCN2) in the development and course of hepatocellular carcinoma (HCC) and to contribute to the evolution of innovative HCC therapeutics.Methods: Oncomine, GEPIA (Gene Expression Profiling Interactive Analysis), TISIDB (Tumor Immune System Interactions and Drug Bank database), UALCAN (University of Alabama at Birmingham Cancer data analysis portal), UCSC (University of California, Santa Cruz), R package, the Kaplan–Meier technique, Cox regression analysis, LinkedOmics, Pearson’s correlation, and a nomogram were used to investigate the prognostic value of FCN2 in HCC. Co-expressed genes were screened. A protein–protein interaction network was created using the STRING database. Finally, immunohistochemistry was performed to establish the expression of FCN2 in HCC tissues. A pan-cancer study centered on HCC-related molecular analysis was also conducted to look for a link between FCN2 and immune infiltration, immune modulators, and chemokine receptors.Results: In HCC tissues, the expression of FCN2 was observed to be lower than that in normal tissues. This was connected to the HCC marker alpha-fetoprotein, showing that FCN2 is involved in the development and progression of cancer. FCN2 may act through Staphylococcus aureus infection, lectins, and other pathways. Furthermore, at the immune level, the expression of FCN2 in HCC was associated with some immune cell infiltration, immunomodulators, and chemokine receptors.Conclusion: FCN2 may be an immune checkpoint inhibitor for HCC, creating a breakthrough in the treatment of HCC.

Cervical adenocarcinoma (CA) is a type of cervical cancer, and in previous decades its incidence has steadily increased. The upregulation of regucalcin (RGN) in various tumor cell types inhibits the progression of cancer. To understand the role of RGN in CA, RGN expression in human cervical cancer compared with normal tissues was analyzed using The Cancer Genome Atlas database (TCGA). Subsequently, transfection of lentivirus‑mediated RGN into HeLa cells was conducted to study its function in tumor proliferation and metastasis. The expression of RGN and proteins associated with the Wnt/β‑catenin signaling pathway and epithelial‑mesenchymal transition (EMT) were determined using reverse transcription‑quantitative polymerase chain reaction and western blotting. Cell migration and invasion were evaluated using Transwell assays. Furthermore, cell proliferation, colony formation and cell cycle were assessed using the Cell Counting Kit‑8, colony formation assay and flow cytometry, respectively. Lentivirus‑mediated RGN effectively upregulated RGN expression, inhibited cell proliferation, retarded cellular invasion and promoted cell cycle arrest at the G2/M phase in HeLa cells. In addition, the expression levels of β‑catenin, p‑glycogen synthase kinase (GSK)‑3β, matrix metalloproteinase (MMP)‑3, MMP‑7 and MMP‑9 were effectively decreased, whilst those of E‑cadherin and GSK‑3β were increased. The results suggest that RGN may be an inhibitory factor in tumorigenesis, and its mechanism of inhibiting tumor proliferation and metastasis may be associated with Wnt/β‑catenin signaling and EMT.

Introduction: Hepatocellular carcinoma (HCC) presents great difficulties for diagnosis and prognosis. Metabolic reprogramming and ferroptosis resistance play critical roles in HCC development and progression. Methods: We combined transcriptome data from TCGA-LIHC to screen out lactylation-ferroptosis-related genes (LFRGs). Based on LASSO-Cox regression and multivariate analysis, a 4-gene-prognostic signature (STMN1, PRDX1, TP53, G6PD) was constructed. Results: The signature stratified HCC patients into two risk subgroups with obvious survival differences (P < 0.001). Functional validation demonstrated that STMN1/PRDX1 knockdown in MHCC-97H/SNU-449 cells could decrease the expression of LDHA (lactylation enzyme) and GPX4 (ferroptosis inhibitor), and further inhibited cell proliferation and migration (P < 0.01). The risk model was positively correlated with tumor stage and TMB, TP53 mutation, and immunosuppressive microenvironment. Drug sensitivity profile analysis suggested that high-risk patients may be sensitive to Dactolisib/Trametinib, while low-risk patients showed resistance to Axitinib/Ibrutinib. Mechanistically, STMN1/PRDX1 act as dual hubs in lactate metabolism (stabilizing LDHA) and ferroptosis resistance (modulating GPX4). Discussion: We identified the first lactylation-ferroptosis cross-talk signature to predict HCC prognosis and identified STMN1/PRDX1 as potential targets for treating HCC by stratifying therapies.