Discover. Oncology最新文献

Background: Patients with unmethylated O6-methylguanine-DNA methyltransferase promoter (uMGMT) glioblastoma (GBM) have a poor prognosis. Inflammatory response can affect the prognosis, for it may have a significant impact on the tumor microenvironment (TME). This study aims to identify a prognostic signature of inflammation-related genes, which can predict the prognosis of uMGMT GBM patients.

Methods: We examined the gene expression, somatic mutations, and overall survival of 159 GBM patients with uMGMT using the TCGA and CGGA databases. We identified molecular subtypes of uMGMT GBM patients based on the expression of inflammation-related genes. Furthermore, we determined principal component analysis (PCA), gene ontology (GO) analysis, pathway analysis and immune infiltration analysis between high and low-inflammation subtypes. We also examined the spatial and longitudinal heterogeneity of these two subtypes. The LASSO-Cox analyses were used to develop an inflammation-related prognostic model.

Results: Our findings indicate that patients with uMGMT GBM can be divided into high-inflammation and low-inflammation subtypes. Patients with high levels of inflammation are more likely to develop an immunosuppressive microenvironment, which stimulates the production of immunosuppressive cytokines, immune checkpoints, and immunosuppressive cells. Nine inflammation-related genes (EREG, BDKRB1, DCBLD2, CD14, AHR, CLEC5A, LTA, SLC4A4, and LY6E) were found to have excellent predictive potential for patient survival in the prognostic model.

Conclusions: In conclusion, we created a new prognostic model including 9 inflammation-related genes. This model has produced meaningful results in evaluating patient prognosis, which may help with future therapeutic strategies for patients with uMGMT GBM.

Background: Histamine, a critical inflammatory mediator, is generated by both mast cells and specific tumor cells, and it plays a fundamental role in inflammatory and immune responses. In the current scientific landscape, histamine-related genes (HRGs) and their associated pathways have been validated to be implicated in the development and advancement of cancer. However, the precise role of HRGs in gauging the risk and predicting the prognosis of pancreatic adenocarcinoma (PAAD) remains nebulous.

Methods: We carried out an elaborate data collection endeavor. Transcriptome data along with pertinent clinical information were obtained from the GSE28735, GSE62452, and TCGA-PAAD cohorts. GWAS data were retrieved from the FinnGen Release 11 and eQTLGen databases. For the drug-target Mendelian randomization (MR) analysis, the "TwoSampleMR" (version 0.5.6) R package was employed. The random survival forest (RSF) model was analyzed using the "randomForestSRC (rfsrc)" R package and further elucidated with the help of the "mlr3" package. Somatic mutation analysis and immune infiltration investigations were conducted by means of the "maftools" (v. 2.12.0) R package and "pRRophetic" R software package, respectively. Targeted drug sensitivity analysis was executed using the "oncopredict" and "parallel" packages.

Results: Through a meticulous drug-targeted MR analysis and an exhaustive exploration of transcriptome databases (including 2 GSE combat and TCGA cohort), 20 upregulated differentially expressed genes (DEGs) were identified. The RSF model emerged as the optimal choice, and a 9-HRGs signature was selected to construct a prognostic model that boasted an average C-index of 0.777. In the training and validation cohorts, the model exhibited remarkable predictive prowess, with 1-, 2-, and 3-year prediction accuracies of 0.898, 0.932, and 0.922 in the training set, and 0.909, 0.974, and 0.962 in the validation set, respectively. A higher HRG score was found to correlate with adverse events and the N1 stage. Additionally, it was associated with an increase in M0 macrophages and a decline in CD8 + T cell function. For patients with a low HRG score, several commonly used chemotherapeutic agents, namely Gemcitabine, Carboplatin, Sorafenib, and Oxaliplatin, were more efficacious.

Conclusion: The HRG signature holds the potential to serve as effective biomarkers for diagnosing, predicting the prognosis, and assessing the sensitivity to chemotherapy in PAAD.

Phosphoglycerate mutase 1 (PGAM1) has been identified as a key player in the progression and metastasis of various human cancer types, including breast cancer (BC); however, its precise oncogenic mechanism remains unclear. The present study aimed to investigate the oncogenic mechanisms of PGAM1 and establish its potential as a therapeutic target. Comprehensive analyses from the Tumor Immune Estimation Resource 2.0 and The Cancer Genome Atlas databases revealed a significant upregulation of PGAM1 in BC, correlating with poor clinical outcomes. Additionally, elevated expression of PGAM1 was confirmed in clinical BC samples. Silencing PGAM1 with specific small hairpin RNA in BC cells resulted in a marked reduction in cell proliferation, invasiveness and migration, alongside increased apoptosis and cell cycle arrest. In vivo experiments using tumor-bearing nude mice demonstrated that PGAM1 knockdown significantly reduced tumor volume and weight, effectively inhibiting tumor growth. Mechanistic investigations suggested that PGAM1 promoted BC tumorigenesis through the activation of the Wnt/β-catenin signaling pathway, both in vitro and in vivo. Therefore, the upregulation of PGAM1 in BC enhances malignancy via the Wnt/β-catenin signaling pathway, highlighting PGAM1 as a promising therapeutic target for BC treatment.

Hairy and enhancer of Split 4 (HES4) is thought to have a substantial impact on the pathogenesis and progression of malignancies. However, the prognostic significance and mechanism of HES4 have not been reported in Hepatocellular carcinoma (HCC). A comprehensive bioinformatics analysis of HES4 expression, clinicopathological characteristics, tumor microenvironment status, and drug sensitivity were performed based on TCGA, GTEx, and GEO. Paired HCC samples and cell lines were used to validate the dysfunction of HES4 in vitro. The expression of HES4 at both mRNA and protein levels was significantly upregulated in HCC tissues. High level of HES4 was associated with unfavorable outcomes. Enrichment analysis demonstrated strong associations of HES4 with HCC progression pathways. In addition, elevated HES4 expression was positively correlated with increased sensitivity to various chemotherapy drugs and associated with resistance to immunotherapy. As a transcription factor, the target genes regulated by HES4 were mostly risky genes, and a novel prediction model based on HES4 target genes was generated for HCC risk stratification. The AUCs of 1-, 3-, and 5-year year overall survival (OS) were 0.829, 0.732, and 0.700, respectively. HES4 overexpression is associated with poor clinical outcomes and tumor progression. HES4 may serve as a novel prognostic marker and therapeutic target in HCC.

Background: Ferroptosis, an iron-dependent form of programmed cell death, has been implicated in various types of cancer. However, the association between ferroptosis-related long noncoding RNAs (FRLs) and multiple myeloma (MM) remains unclear. This study aimed to develop an FRL-based predictive model to assess its potential role in predicting overall survival prognosis and evaluating immune cell infiltration and chemotherapy response in MM patients.

Methods: We identified FRLs using the GEO and FerrDb databases and employed univariate Cox regression and least absolute shrinkage and selection operator (LASSO) to establish a prognostic FRLs signature in the training cohort. The reliability of the risk model was evaluated using Kaplan-Meier (K-M) and time-dependent receiver operating characteristic (ROC) curve analyses. Gene set enrichment analysis (GSEA) was conducted to explore the biological functions associated with the FRLs signature. We also assessed immune cell infiltration and estimated the IC50 of drugs using the R package 'pRRophetic'. The expression of FRLs was validated by qRT-PCR.

Results: We established a novel 8 FRLs signature, comprising AC005592.1, AC093714.1, AC104041.1, AL122058.1, DIRC1, ERVH-1, FAM223B, and TDRKH-AS1. The risk model was identified as an independent risk factor for overall survival (OS) in MM patients. Bioinformatics analysis indicated that the high-risk group exhibited activation of carcinogenic signaling pathways and immune cell infiltration. The qRT-PCR confirmed the significant upregulation in the expression of ERVH-1, TDRKH-AS1, and AC104041.1, and the downregulation of DIRC1, AC005592.1, AC093714.1, and AL122058.1 in MM samples. Furthermore, the ferroptosis inducer erastin triggered ferroptosis, inhibited cell viability, and upregulated TDRKH-AS1.

Conclusion: Our study highlights the potential of the FRLs signature as a prognostic tool and its implications for therapeutic strategies in MM.

Lung cancer stands out as a significant global health burden, with staggering incidence and mortality rates primarily linked to smoking and environmental carcinogens. The tumor microenvironment (TME) emerges as a critical determinant of cancer progression and treatment outcomes, comprising a complex interplay of cells, signaling molecules, and extracellular matrix. Through a comprehensive literature review, we elucidate current research trends and therapeutic prospects, aiming to advance our understanding of TME modulation strategies and their clinical implications for lung cancer treatment. Dysregulated immune responses within the TME can facilitate tumor evasion, limiting the efficacy of immune checkpoint inhibitors (ICI). Consequently, TME modulation strategies have become potential avenues to enhance therapeutic responses. However, conventional TME-targeted therapies often face challenges. In contrast, nanoparticle (NP)-based therapies offer promising prospects for improved drug delivery and reduced toxicity, leveraging the enhanced permeability and retention (EPR) effect. Despite NP design and delivery advancements, obstacles like poor tumor cell uptake and off-target effects persist, necessitating further optimization. This review underscores the pivotal role of TME in lung cancer management, emphasizing the synergistic potential of immunotherapy and nano-therapy.

Metastatic intracranial progression drastically impacts prognosis, therapeutic considerations and quality of life. The increasing incidence of lung cancer patients developing brain metastases (BM) parallels the incorporation of more effective systemic agents and improved surveillance. Our evolving knowledge of BM pathophysiology, along with advancements in surgical, radiotherapy and systemic therapy options, is rapidly changing prognostication and treatment paradigms. Optimal management of BM in the modern era is patient-specific, dependent on performance status, comorbidities, intracranial and extracranial disease burden, leptomeningeal disease, and the presence of targetable mutations. The purpose of this review is to provide a detailed overview of the detection, prognostication, and multidisciplinary, management of BM arising from non-small cell lung cancer and small cell lung cancer. We discuss contemporary evidence and active clinical trials supporting a wide array of treatment options, including surgery, radiosurgery, memory-avoidance whole brain radiation, craniospinal irradiation, chemotherapy, targeted agents and immunotherapy. Multidisciplinary paradigms will continue to evolve as currently accruing randomized trials evaluating these promising treatments options mature.

Objective: The mechanism of glioma development has been extensively explored and comprehension of the exosomal microRNA-142-3p/growth factor independent-1 (miR-142-3p/GFI1) axis in glioma is still at an initial stage. Therein, the conducted work goes toward ascertaining the role of the bone marrow mesenchymal stem cells-derived exosomes (BMSCs-Exos)/miR-142-3p/GFI1 axis in glioma development.

Methods: Cancer tissues from patients with glioma and normal brain tissues from those who underwent surgery for traumatic brain injury were collected. miR-142-3p and GFI1 expression in tissues and cells were measured. Exos derived from BMSCs carrying miR-142-3p were cocultured with glioma cells to observe the effects of exosomal miR-142-3p on glioma cell invasion, migration, and apoptosis. The targeting relationship of miR-142-3p and GFI1 was validated. A series of rescue assays were conducted to further investigate whether GFI1 is implicated in the exosomal miR-142-3p-mediated regulation of glioma cell invasion, migration, and apoptosis.

Results: miR-142-3p was low-expressed in glioma tissues and cells, and the low expression had an association with unwanted prognosis. Exos-shuttled miR-142-3p suppressed the migration and invasion, while promoting apoptosis of glioma cells. Further investigation revealed that GFI1 was a direct target of miR-142-3p, and re-expression of GFI1 neutralized the inhibitory effects of exosomal miR-142-3p.

Conclusion: Exosomal miR-142-3p suppressed glioma cell migration and invasion and stimulated apoptosis by targeting GFI1.

Ferroptosis is a novel mode of iron-dependent non-apoptotic cell death that occurs mainly due to excessive accumulation of lipid peroxides. Numerous studies in recent years have shown that ferroptosis plays a vital role in the organism and has important interactions with immune cells. Ferroptosis has been shown to have great potential in tumour therapy through studying its mechanism of action. In addition, ferroptosis plays a major role in many types of tumour cells that can potently suppress the tumourigenesis and metastasis, provide a basis for the treatment of many malignant tumour diseases and become a novel therapeutic modality of antitumour immunity in the clinic. Current tumour immunotherapy for ferroptosis in combination with other conventional oncological modalities is not well elaborated. In this paper, we mainly discuss the connection of ferroptosis with immune cells and their mediated tumour immunotherapy in order to provide a better theoretical basis and new thinking about ferroptosis mediated antitumour immunity.

Objective: This study aims to investigate the role of BRAF-activated long non-coding RNA (BANCR) in papillary thyroid carcinoma (PTC) progression and its association with clinical and molecular characteristics.

Methods: Sixteen PTC patients were stratified into four groups (PTC, HT, HT-LNM, and PTC-LNM) based on cervical lymph node metastasis and concurrent Hashimoto's thyroiditis (HT) to explore BANCR expression and its relationship with immune-related factors and tumor microenvironment (TME). Functional assays, including Transwell invasion, colony formation, and CCK8 were performed to evaluate the biological effects of BANCR in PTC cell lines. Bioinformatics analysis further identified BANCR-related pathways and clinical relevance.

Results: BANCR expression was significantly reduced in PTC tissues compared to normal thyroid tissues and was inversely correlated with tumor grade, lymph node metastasis, and T stage. Overexpression of BANCR in PTC cell lines inhibited proliferation, invasion and migration. Bioinformatics analysis demonstrated significant associations between BANCR and immune cell infiltration, immune-related genes, and stromal scores.

Conclusions: BANCR acts as a tumor suppressor in PTC, suppressing tumor growth and metastasis. These findings provide insights into BANCR's potential as a prognostic marker and therapeutic target in PTC.