Journal of Cancer最新文献

Background: Glioblastoma (GBM) is the most prevalent and aggressive type of primary brain tumor in adults. Fatty acid metabolism plays a crucial role in promoting tumorigenesis, disease progression, and therapeutic resistance through the regulation of lipid synthesis, storage, and catabolism. However, its potential for predicting both prognosis and treatment response in glioblastoma is unexplored. Methods: We systematically compiled fatty acid metabolism-related genes (FAMGs) from published literature and databases. A fatty acid metabolism signature (FAMS) was developed using a machine learning-based framework. The predictive performance of the FAMS was rigorously validated across multiple independent cohorts. Additionally, we investigated the associations between FAMS and clinical characteristics, mutation profiles, tumor microenvironment features, and biological functions. Results: Our analysis revealed distinct FAMGs expression patterns in patients with GBM, which correlated with varying survival outcomes. Leveraging a robust machine learning framework, we established a fatty acid metabolism-based prognostic model. The FAMS emerged as an independent predictor of overall survival and other survival endpoints. Patients with lower FAMS exhibited enrichment in mitosis- and DNA repair-related pathways, which is linked to better survival. Conversely, higher FAMS scores were associated with enhanced immune activation, cellular proliferation, and chemotaxis, suggesting a greater likelihood of benefitting from immunotherapy. Conclusion: We developed a reliable fatty acid metabolism signature capable of stratifying GBM patients on the basis of prognosis. The FAMS serves as an independent prognostic indicator and may offer clinical utility in guiding personalized treatment strategies for patients with GBM.

Cancer incidence and mortality rates are on the rise, with ovarian cancer being a significant concern globally. HKDC1 is identified as a crucial protein involved in cancer metabolism, particularly in lung, liver, colorectal, and gastric cancers. Its upregulation correlates with poor clinical outcomes and promotes tumor progression through various mechanisms, including enhanced glycolysis and immune evasion. The exploration of HKDC1's role in cancer offers potential for new therapeutic strategies and biomarkers in cancer treatment.

Nanoparticle carriers can selectively deliver the drug cargo to tumor cells, thus having the ability to prevent early drug release, reduce non-specific cell binding, and prolong in vivo drug retention. We constructed paclitaxel (PTX)-loaded lipid-shell mesoporous silica nanoparticles (LMSNs) for targeted anti-cancer drug delivery. The physical properties of PTX-LMSNs were analyzed by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The drug loading (DL%) and entrapment efficiency (EE%) of PTX-LMSNs were measured by high performance liquid chromatography (HPLC). In vitro drug release test, in vivo imaging, tissue distribution and pharmacokinetics of PTX-LMSNs were also evaluated. The SEM examination showed that MSNs were sphere, whereas TEM showed that they were rich in fine pores. The uniform core-shell structure of PTX-LMSNs was also verified by TEM. The DL capacity of PTX-LMSN was as high as 21.75%, and PTX was released from the nanoparticles in vitro in a pH-dependent manner. The cumulative amount of free PTX increased at lower pH, which is conducive to selective drug release from LMSNs in the acidic tumor tissues. In vivo imaging showed prolonged retention of PTX-LMSNs, which is beneficial to their therapeutic efficacy. In addition, PTX-LMSNs were primarily concentrated in the liver. Pharmacokinetic experiments showed that the half-life of PTX-LMSNs was 23.21% longer and 79.24% higher than that of Taxol. Together, LMSNs are a highly promising antineoplastic drug carrier system.

Background: Lung adenocarcinoma (LUAD) continues to pose a major challenge in cancer treatment, characterized by low survival rates, particularly in metastatic instances. Although immunotherapy has become a common approach for treating LUAD, its success rate is merely 20%, hindered by the absence of effective biomarkers. This limitation is likely influenced by the tumor's immune microenvironment. CD40LG, an important immune molecule, has emerged as a crucial factor in modulating the tumor immune environment and affecting the outcomes of immunotherapy. Nevertheless, its exact mechanisms in LUAD remain unclear, requiring more research. Methods: Through a correlation analysis of prognosis and clinical traits across multiple cancers, we determined that CD40LG is significant in LUAD. This role was confirmed using various public datasets. We evaluated CD40LG protein expression in 94 LUAD and nearby non-cancerous tissues via immunohistochemistry. To gauge immune cell infiltration, we employed multiplex immunofluorescence staining on tissue microarrays. Additionally, in vitro assays were carried out to explore the effects of CD40LG modulation on the behavior of LUAD cells. Results: Various cancers, including LUAD, exhibited down-regulation of CD40LG, which correlated with a worse prognosis. In LUAD tissues, higher CD40LG expression was associated with longer Progression-Free Survival (PFS) and Overall Survival (OS). Moreover, CD40LG expression negatively correlated with the TNM stage and T stage in LUAD. Elevated CD40LG levels were linked to increased infiltration of CD8+ T cells. In vitro studies showed that modulating CD40LG affected LUAD cell metastasis and proliferation. Conclusion: Our study demonstrates the pivotal role of CD40LG in LUAD, proposing its potential utility as a biomarker for prognosis and immunotherapy. The correlation between CD40LG expression, immune cell infiltration, and clinical outcomes emphasizes its importance in tumor-immune dynamics and the efficacy of immunotherapy.

Emerging evidence has demonstrated that pseudouridylation regulates mRNA translation and gene expression, yet its molecular characteristics in hepatocellular carcinoma (HCC) remain unknown. Using public databases, we developed pseudouridylation-related molecular subtype and risk score model to assess HCC patient prognosis and disclose their clinical feature, molecular mechanism and immune landscape. Furthermore, quantitative polymerase chain reaction (qPCR) was performed to verify the expression of RDM1, CDCA3 and FLVCR1. Specifically, functional enrichment analysis revealed pseudouridylation-related genes (PRGs) predominantly regulate transcriptional and translational regulation. Prognostic PRGs stratified HCC into two distinct subtypes, the cluster 1 had a poor prognosis and was characterized by high alpha fetoprotein level, poor differentiation, advanced tumor stage, large tumor size, frequent TP53 mutation, up-regulation of cell cycle- and mitosis-associated genes, which was similar to the aggressive proliferation subtype of HCC. In contrast, the cluster 2 exhibited good prognosis and increased infiltration of immune cells, resembling the non-proliferation subtype of HCC, and suggesting its potential responsiveness to immunotherapy. Survival analysis discovered that the risk score model served as an independent prognostic factor, with high-risk group exhibiting significantly shorter overall survival and recurrence-free survival than low-risk group. Notably, receiver operating characteristic analysis revealed that the risk model had a powerful predictive performance for 1- and 3- year survival (AUC=0.806). In addition, functional enrichment analysis suggested that upregulated genes of high-risk group displayed an enrichment of cell cycle progression, mitotic division, and some oncogenic signaling pathways (PLK1, FOXM1, and p53 signaling pathways). qPCR experiment confirmed the significant overexpression of RDM1, CDCA3, and FLVCR1 in HCC tissues, being consistent with public database analysis. In conclusion, pseudouridylation related-molecular subtype and risk model may effectively predict the prognosis and therapeutic response of HCC.

The B-cell CLL/lymphoma 6B (BCL6B) gene, a homolog of BCL6, belongs to the ZBTB (zinc finger and BTB domain-containing) protein family and functions as a transcriptional repressor involved in gene regulation and cellular proliferation. In recent years, BCL6B has garnered increasing attention due to its critical involvement in various biological processes, including tumor suppression, immune modulation, stem cell maintenance, and angiogenesis. Moreover, its dysregulation, often through epigenetic modifications such as promoter hypermethylation, has been implicated in the pathogenesis of several malignancies and immune-related disorders. This review provides a comprehensive overview of BCL6B's molecular functions, its roles in human disease, and emerging research advances, highlighting its potential as both a diagnostic biomarker and a therapeutic target.

Background: Novel advanced melanoma therapy combinations may increase treatment efficacy and reduce treatment-related toxicities. Methods: This open-label, nonrandomized, multicenter, phase 1b, 3-arm, umbrella study enrolled patients with advanced melanoma eligible for standard-of-care checkpoint inhibitor therapy. There were 3 phases: dose escalation; Part 1 limited cohort expansion; Part 2 additional expansion. Arms (A) 1, 2, and 3 investigated tovorafenib plus nivolumab, plozalizumab plus nivolumab, and vedolizumab plus nivolumab plus ipilimumab, respectively. In the dose-escalation plus Part 1 limited cohort expansion phase, the primary endpoint was dose-limiting toxicities. Results: Twenty-two patients (A1=1; A2=9; A3=12) were enrolled before premature study termination. A1 was closed due to lack of enrollment. A2 enrollment was closed due to lack of clinical benefit (6/9 patients discontinued due to disease progression), and A3 enrollment was closed due to meeting prespecified stopping criteria (grade 3 diarrhea/colitis in 2 patients). One patient (A2) experienced dose-limiting toxicities. Grade ≥3 adverse events were reported in the single patient from A1, 3 (33.3%) patients from A2, and 10 (83.3%) patients from A3. Conclusion: Study design allowed early termination after initial results suggested unlikely clinical benefit. Efficacy remains inconclusive for tovorafenib plus nivolumab and vedolizumab plus nivolumab plus ipilimumab in advanced melanoma. Trend review in this small population suggests a limited effect of investigated vedolizumab regimens as primary prophylaxis against nivolumab plus ipilimumab gastrointestinal toxicity.

Osimertinib is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI); it has achieved favorable progression-free survival (PFS) in non-small cell lung cancer (NSCLC) patients with EGFR mutation, however, the resistance occurs in most patients, and the underlying mechanism remain to be elucidated. Cancer-associated fibroblasts (CAFs) are major stromal cells in tumor microenvironment. Despite accumulating evidence suggests that CAFs contribute to drug resistance, the role of CAFs in osimertinib resistance in NSCLC is not fully understood. Here, we reported that CAFs promoted the resistance of NSCLC cells to osimertinib through enhancing stemness of NSCLC cells and reducing apoptosis induced by osimertinib. CAFs possessed a high level of Neuregulin-1 (NRG1), and CAFs-secreted NRG1 mediated the promoting effect of CAFs on osimertinib resistance, demonstrated by applying recombinant human NRG1 (rhNRG1) and NRG1 knockdown. We also found that osimertinib stimulated NRG1 secretion by CAFs, which may further enhance osimertinib resistance. Further study revealed that CAFs promoted the resistance of NSCLC cells to osimertinib via NRG1-mediated HER3/AKT/NF-κB pathway. Moreover, the mouse xenograft study demonstrated that CAFs enhanced osimertinib-treated tumor growth in vivo. Our finding highlights the potential value of CAFs-derived NRG1 as a novel therapeutic target for osimertinib resistance in lung cancer.

One of the most prevalent cancers and a major global cause of mortality in men is prostate cancer (PCa). Omentin-1, an adipokine, has been shown to play a protective role by reducing proinflammatory cytokine secretion. The relationships among carcinogenic lifestyle factors, biochemical recurrence (BCR), OMNT1 polymorphisms, and PCa remain unclear. We investigated the impact of clinicopathological features and four OMNT1 gene variants on PCa risk in 701 Taiwanese male patients with and without BCR. Compared with the TT genotype, the TA+AA genotypes of SNP rs2274907 were associated with a lower risk of perineural invasion. Similarly, the AG+GG genotypes of rs4656959 were associated with a lower risk of perineural invasion compared to the AA genotype. Importantly, PCa patients without BCR exhibited the same effects. Interestingly, the wild-type TT homozygous genotype was associated with significantly lower OMNT1 expression levels compared to the AA genotype of the rs2274907 variant. Additionally, OMNT1 mRNA levels were lower in PCa tissues compared to normal tissues, indicating that omentin-1 acts as a protective factor in PCa.