American journal of cancer research最新文献

The OTU family consists of 16 highly conserved deubiquitinases (DUBs) that play critical roles in regulating diverse signaling pathways through substrate-specific deubiquitination of key proteins. These enzymes are involved in multiple physiological processes, including cancer progression, immune responses, cell division, and inflammation modulation. Depending on their target substrates, individual OTU family members perform distinct functions across biological processes, as exemplified by their dual roles in cancer pathogenesis. Increasing attention has been directed toward developing OTU DUB inhibitors as potential cancer therapeutics. This review provides a systematic analysis of recent structural and functional studies on OTU family members, with a particular focus on their roles in cancer. We discuss their associations with various malignancies and summarize advances in OTU-targeted inhibitor development, emphasizing their clinical potential as novel therapeutic targets.

Hepatocellular carcinoma (HCC) is a major global health challenge, with poor prognosis for advanced patients. Centromere proteins (CENPs) play a critical role in maintaining genomic stability. To investigate the characteristics of CENPs in HCC and elucidate the mechanisms by which CENPs regulate HCC progression through interactive molecular networks, this review aims to provide new insights into HCC mechanisms and targeted therapies. Therefore, we retrieved peer-reviewed original research articles or reviews from the PubMed database, focusing on the current research status of CENPs in HCC, and detailed the expression levels of CENPs in HCC tissues, patient survival, clinicopathological features, immune infiltration, and intermolecular mechanisms. The study found that aberrant expression of CENPs has been confirmed to be significantly associated with HCC patient survival, clinicopathological characteristics, and tumor microenvironment immune infiltration. CENPs regulate HCC cell proliferation, invasion, migration, cell death, angiogenesis, and glycolysis through complex interactive molecular networks. This review provides valuable insights for basic research, the development of HCC biomarkers, and the research and development of targeted drugs.

Objective: To investigate the mechanism by which the CBX4-HDAC5-CERS6 axis regulates sphingolipid metabolism in acute myeloid leukemia (AML), with the goal of providing new theoretical foundations for the targeted therapy of AML.

Methods: This prospective study involved 50 AML patients and 50 healthy controls. The expression levels of CBX4, CERS6, and free ceramide were detected. RNA sequencing, proteomics, and lipidomics were employed to analyze CBX4's regulatory effects on sphingolipid metabolism-related genes and pathways. Using THP-1 and KG-1 cell lines, we validated the molecular mechanisms of the CBX4-HDAC5-CERS6 axis through techniques including gene knockdown (siRNA), overexpression, chromatin immunoprecipitation (ChIP), and dual-luciferase reporter assays. CCK-8 assay, flow cytometry, and Western blot were used to analyze the effects of CBX4 on cell proliferation, cell cycle, and key signaling pathways.

Results: CBX4 was significantly overexpressed in AML cells, with its expression levels markedly higher in THP-1 and KG-1 cell lines compared with CD34⁺ normal hematopoietic stem cells (P<0.05). Analysis of clinical samples revealed that the mRNA expression levels of CBX4 and CERS6 as well as free ceramide content were significantly lower in the AML group than the control group (all P<0.05). Mechanistic studies demonstrated that CBX4 knockdown significantly downregulated both mRNA and protein expression of CERS6 (P<0.05) and activated the PI3K/AKT and MAPK signaling pathways. Furthermore, CBX4 indirectly regulated CERS6 transcription by suppressing HDAC5 expression, and dual-luciferase reporter assays confirmed that HDAC5 directly targets the CERS6 promoter region (P<0.05). Combined use of ceramide synthesis inhibitors synergistically enhanced the activation of p-AKT/p-PI3K and p-MEK1/2/p-Raf1 signaling pathway associated proteins induced by CBX4 knockdown.

Conclusion: The CBX4-HDAC5-CERS6 axis influences AML malignant progression by regulating sphingolipid metabolism, and targeted intervention of this axis may represent a novel therapeutic strategy for AML.

[This corrects the article on p. 2537 in vol. 11, PMID: 34249415.].

This study aimed to assess the diagnostic value of combining computed tomography (CT) and magnetic resonance imaging (MRI) for differentiating pancreatic cancer (PCa) from chronic pancreatitis (CP). A total of 340 patients with pancreatic diseases were retrospectively included, comprising 173 cases of PCa and 167 cases of CP. The patients were randomly divided into a training set of 238 cases and a validation set of 102 cases, with the validation set comprising 52 cases of PCa (Group A) and 50 cases of CP (Group B). All patients underwent multi-slice spiral CT (MSCT) and multi-parametric MRI examinations. Imaging features and CT attenuation values were analyzed. Diagnostic sensitivity (Sen), specificity (Spe), and accuracy (Acc), and the area under the receiver operating characteristic curve (AUC) were compared among CT, MRI, and their combined application. The inter-group comparison indicated that pancreatic volume enlargement, invasion of surrounding tissues and major blood vessels, peripheral lymph node enlargement, inconspicuous arterial phase (AP) enhancement, and smooth dilation of the pancreatic duct (PD) and bile duct (BD) in Group A were markedly higher than those in Group B. Conversely, lesion calcification, fibrosis and pseudocyst formation, and irregular dilation of the PD and BD were less common in Group A than in Group B (P<0.001 for pancreatic enlargement, surrounding tissue/vessel invasion, peripheral lymph node enlargement, inconspicuous AP enhancement, smooth ductal dilation, and lesion calcification; P=0.001 for fibrosis and pseudocyst formation; P=0.012 for irregular ductal dilation). The CT attenuation values of Group A were markedly lower than those of Group B during the AP, portal venous phase (PVP), and delayed phase (DP) (all P<0.001), whereas the apparent diffusion coefficient (ADC) values were significantly higher (1.463 ± 0.098 vs. 1.158 ± 0.134, P=0.000). In the training set data, the efficacy of the CT+MRI diagnosis of PCa and CP (Sen=96.2%, Spe=92%, Acc=96%, AUC=0.972) was significantly better than that of CT alone (Sen=86.5%, etc.) and MRI alone (Sen=88.5%, etc.), with statistically significant differences in all compared indicators (P<0.05 or P<0.001). In the validation set, the efficacy of the CT+MRI diagnosis of PCa and CP (Sen=93.4%, Spe=89.7%, Acc=91.6%, AUC=0.951) was significantly better than that of CT alone (Sen=84.3%, etc.) and MRI alone (Sen=86%, etc.), with statistically significant differences in all compared indicators (all P<0.05), and the efficacy trend was completely consistent with that of the training set. In summary, the combined application of CT and MRI provides superior Sen, Spe, and Acc for differentiating pancreatic cancer from chronic pancreatitis compared with either modality alone.

Background: Visceral obesity-related genes (VORGs) have been implicated in cancer progression, but their biological and clinical relevance in ovarian cancer (OC) remains uncertain.

Methods: Prognostic modeling of VORGs was carried out using the The Cancer Genome Atlas (TCGA) and GSE53963 datasets. This model was further investigated in its association with tumor immunity, immune checkpoint inhibitor (ICI) response, and chemotherapy outcomes. Additionally, single-cell data were analyzed to explore gene expression within the tumor microenvironment of this model, specifically identifying high expression of the key gene MARVELD1 in tumor stem cells. The functionality of MARVELD1 was validated experimentally through Cell Counting Kit-8 (CCK-8), transwell, and colony formation assays.

Results: OC patients were stratified into four molecular subtypes based on overall survival (OS)-associated VORG expression profiles. Differentially expressed genes (DEGs) between subtypes with prognostic relevance were identified and subsequently analyzed using least absolute shrinkage and selection operator (LASSO) regression and stepwise Cox modeling, resulting in a robust four-gene prognostic model comprising CXCL9, IGF2, FCGBP, and MARVELD1. This model effectively classified patients into high- and low-risk groups, with the high-risk group demonstrating significantly poorer outcomes (P < 0.001). In addition, risk scores showed strong correlations with immune checkpoint gene expression and predicted chemotherapy sensitivity, underscoring their utility in forecasting therapeutic responses. Single-cell transcriptomic analysis revealed heterogeneous expression of model genes across subpopulations, with MARVELD1 prominently enriched in tumor stem cells. MARVELD1 was found to modulate early cellular processes through pathways such as reactive oxygen species. Finally, in vitro experiments confirmed that MARVELD1 knockdown significantly inhibited OC cell proliferation, invasion, and colony formation, further validating its oncogenic role.

Conclusion: A VORG-based prognostic model was established that correlates with OC prognosis, tumor immune microenvironment, and treatment sensitivity. These findings suggest that MARVELD1 and related pathways may serve as potential targets to improve prognostic stratification and guide therapy in OC.

[This corrects the article on p. 2142 in vol. 11, PMID: 34094674.].

[This corrects the article on p. 458 in vol. 11, PMID: 33575081.].

Hepatocellular carcinoma (HCC) is one of the most common types of cancer worldwide. It is characterized by an extremely poor prognosis. Radiofrequency ablation (RFA) and microwave ablation (MWA) have become the main local therapies for early HCC. Nevertheless, the high recurrence rate is a key factor that limits the efficacy of thermal ablation. Numerous studies have suggested that HCC recurrence after thermal ablation involves many mechanisms. These include remodeling of immunosuppressive microenvironment, evasion of programmed cell death, metabolic reprogramming, reprogramming of metabolic adaptation, activation of epigenetic aberrations, acquisition of stemness traits, enhancement of epithelial-mesenchymal transition (EMT), induction of angiogenesis, and regulation by non-coding RNAs. To tackle these underlying mechanisms, precision intervention strategies have been gradually developed. These included, but were not limited to, immune-targeted therapy, modulation of cell death pathways, regulation of metabolic pathways, epigenetic therapeutic strategies, stem cell inhibition interventions, EMT reversal therapy, anti-angiogenesis interventions, and multi-target combination strategies. Our review systematically summarizes the research progress from 2017 to 2025, classifying the multidimensional molecular mechanisms and precision intervention strategies for HCC recurrence following thermal ablation. This provides a theoretical foundation for individualized comprehensive treatment and future research directions.