Discover. Oncology最新文献

Regulatory T cells (Tregs) have been found to be related to immune therapeutic resistance in kidney cancer. However, the potential Tregs-related genes still need to be explored. Our study found that patients with high Tregs activity show poor prognosis. Through co-expression and differential expression analysis, we screened several Tregs-related genes (KTRGs) in kidney renal clear cell carcinoma. We further conducted the univariate Cox regression analysis and determined the prognosis-related KTRGs. Through the machine learning algorithm-Boruta, the potentially important KTRGs were screened further and submitted to construct a risk model. The risk model could predict the prognosis of RCC patients well, high risk patients show a poorer outcomes than low risk patients. Multivariate Cox regression analysis reveals that risk score is an independent prognostic factor. Then, the nomogram model based on KTRG risk score and other clinical variables was further established, which shows a high predicted accuracy and clinical benefit based on model validation methods. In addition, we found EMT, JAK/STAT3, and immune-related pathways highly enriched in high risk groups, while metabolism-related pathways show a low enrichment. Through analyzing two other external immune therapeutic datasets, we found that the risk score could predict the patient's immune therapeutic response. High-risk groups represent a worse therapeutic response than low-risk groups. In summary, we identified several Tregs-related genes and constructed a risk model to predict prognosis and immune therapeutic response. We hope these organized data can provide a theoretical basis for exploring potential Tregs' targets to synergize the immune therapy for RCC patients.

Activating protein 1 (AP-1) is a transcription factor composed of several protein families, Jun proteins and Fos proteins are the components of AP-1. AP-1 is involved in various cellular processes, such as proliferation, differentiation, apoptosis and inflammation. For tumor cells, AP-1 is considered to be a driver whose activity is associated with dysfunction and the onset, development, invasion, and migration of cancer. In addition, AP-1 has been reported to be involved in the drug resistance and radiation resistance of tumor cells during the treatment process. Therefore, AP-1 is a potential target for cancer therapy. At present, a number of inhibitors targeting AP-1 have been developed and have shown certain anti-cancer effects. However, due to the complex structure and function of AP-1, different structures of AP-1 show different effects in different tumor cells, and more studies are needed to reveal its mechanism of action. This article introduces the relationship between AP-1 and tumor development, summarize the current studies and developments of AP-1 related drugs, and provide the future development values of AP-1.

Nonylphenol (NP) is a common environmental contaminant and endocrine disruptor. Our previous research demonstrated that NP could promote the proliferation and epithelial-mesenchymal transition (EMT) of colorectal cancer (CRC) cells; however, the specific mechanism remains unclear. miRNA sequencing revealed that NP upregulated the expression levels of microRNA(miR)-151a-3p in CRC. Analysis of The Cancer Genome Atlas (TCGA) data revealed increased expression levels of miR-151a-3p in CRC tissues. The present experiments showed that NP could activate the WNT/β-catenin signaling pathway, and promoted the migration and invasion of CRC cells by increasing the expression levels of miR-151a-3p. Through bioinformatics analysis and dual-luciferase reporter assays, Fyn-related kinase (FRK) was identified as a target gene of miR-151a-3p. Knockdown of FRK promoted NP-induced EMT in CRC cells and activated the WNT/β-catenin signaling pathway, while overexpression had the opposite effect. In summary, the present study demonstrated that NP could inhibit FRK expression via miR-151a-3p, activate the WNT/β-catenin signaling pathway, and promote EMT in CRC cells.

Acute myeloid leukemia (AML) has a poor prognosis and high heterogeneity. Most cases of leukemias are caused by environmental factors interacting with the cell's genetic material, but treatment is still dominated by cell cycle drugs. Therefore, there is an urgent need to find reliable biomarkers. Based on the Gene Expression Omnibus database, Kaplan-Meier survival analysis and univariate Cox regression analysis were used to select the genes that had the most significant influence on the prognosis of patients with AML. Quantitative real-time PCR and Western blot were used to assess the effects of small interfering RNA transfection and lentiviral interference on the gene's knockout and overexpression, respectively. These method were also used to confirm the expression levels of the FHL1 gene in the HL60 cell line compared to neutrophils.. Cell Counting Kit-8 and flow cytometry were used to detect the effect of high or low expression of FHL1 on cell viability and apoptosis under the influence of cytarabine and daunorubicin. FHL1 was found to be the most prognostic independent biomarker by GSE12417 screening and GSE37642 validation. FHL1 is highly expressed in AML, and knockdown of FHL1 can increase the sensitivity of AML cells to cytarabine and daunorubicin. FHL1 may play a role as a potential molecular marker and therapeutic target for predicting poor prognosis of AML and for direct treatment (chemotherapy).

RPS6KA1 express disorder is associated with many cancers, but the role in head and neck squamous cell carcinoma (HNSCC) and the specific mechanism is still unclear. We used bioinformatics analysis to explore the role of Ribosomal Protein S6 Kinase A1(RPS6KA1) in HNSCC which were predicted to regulate certain pathway and immune microenvironment to increase the risk in HNSCC. Multiple bioinformatics tools based on the EBI, GEO, TCGA databases and clinical samples were used to analyze the expression of RPS6K1 in HNSCC. Western blot (WB) and PCR results confirmed the upregulation of RPS6KA1 in HNSCC tissues. Flow cytometry was used to validate the relationship between RPS6KA1 and immune cell infiltration in the tumor microenvironment. The correlation of RPS6KA1 with the immune environment was further analyzed, and flow cytometry validation was performed in HNSCC samples. Then, Gene Ontology(GO) and Gene Set Enrichment Analysis(GSEA) analysis were used to explore the pathway which could be regulated by RPS6KA1 in HNSCC. And drug sensitivity analysis was used to the access the relationships between RPS6KA1 and drugs therapeutic effects. EBI, TCGA and GEO databases were used to reveal that RPS6KA1 expression was significantly increased in HNSCC, especially in III + IV HNSCC. And it was related to many types of immune cells and immune adjustment factors and positively correlated with tumor immune score and B cells, but had no significant correlation with CD4⁺ and CD8⁺ T cells. Drug sensitivity analysis revealed that RPS6KA1 has certain predictive value. In this research, we indicated that RPS6KA1 is overexpressed and may serve as a potential diagnostic and therapeutic biomarker in HNSCC.

Introduction: Colorectal cancer (CRC) is the second most common cause of cancer-related deaths globally. The gut microbiota, along with adenomatous polyps (AP), has emerged as a plausible contributor to CRC progression. This study aimed to scrutinize the impact of the FadA antigen derived from Fusobacterium nucleatum on the expression levels of the ANXA2 ceRNA network and assess its relevance to CRC advancement.

Material and methods: The functions of ANXA2 and LINC00460 in CRC have been partially clarified. According to our previous study to identify shared MicroRNA-Interaction-Targets (MITs) between ANXA2 and LINC00460, TargetScanHuman (V7.2) and miRDB databases have been used respectively. The Bioinformatics and Evolutionary Genomics web tool was employed to intersect the sets of shared microRNAs and their common targets. Then, the ANXA2 ceRNA network was constructed. Subsequently, the mRNA, miRNA, and lncRNA expression levels were examined in intestinal biopsy specimens from 30 healthy controls, 30 Adenoma patients, and 30 cases of CRC stage I using qRT-PCR.

Results: Elevated expression levels of FadA, ANXA2, hsa-let-7a-2, and LINC00460 were observed in CRC specimens, followed by AP cases, in comparison to samples from normal individuals. Application of the Spearman test revealed a strong and significant correlation between FadA and LINC00460 (r_S = 0.9311, p < 0.0001). Also, the functional analysis of ANXA2 revealed its impact on CRC progression through JAK-STAT and Hippo signaling pathways.

Conclusion: FadA appears to potentiate CRC progression by inducing the upregulation of LINC00460, consequently leading to the hyperexpression of ANXA2 through the ceRNA network.

Gastric cancer (GC), a prevalent malignancy worldwide, encompasses a multitude of biological processes in its progression. Recently, ferroptosis, a novel mode of cell demise, has become a focal point in cancer research. The microenvironment of gastric cancer is composed of diverse cell populations, yet the specific gene expression profiles and their association with ferroptosis are not well understood. Our study employed single-cell RNA sequencing to thoroughly investigate the transcriptomic profiles and identify differential gene expression in gastric cancer, offering fresh insights into the cellular diversity and underlying molecular mechanisms of this disease. We discovered a set of significantly differentially expressed genes in GC, which may serve as valuable leads for future functional investigations. Subsequent analyses, including gene set intersection and functional enrichment, pinpointed genes implicated in ferroptosis and conducted comprehensive Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses to elucidate their biological roles. In the gene selection and model validation section, critical genes were identified using machine learning algorithms, constructing a model with high predictive accuracy. Besides, distorted immune landscapes were further identified in RBL using ssGSEA analysis such that the complex association of gene expression features and its interaction networks as well as infiltration by various types of immune cells can be more clearly understood. Correlation analysis with different immune cell subtypes showed CTSB as an important regulator in the distributions of cancer infiltrating cells. Single-cell RNA sequencing analysis was utilized to map the cellular composition and gene expression profiles of cells in the gastric cancer microenvironment, which provide critical information for elucidating cellular heterogeneity as well as tumor microenvironment regulation in GC. Moreover, the distribution of FTH1, ZFP36 and CIRBP at different expression levels show new research prospects for functional information of these promoters in tumor microenvironment. In summary, the present study augments our knowledge of molecular mechanisms underlying gastric tumorigenesisa and provide scientific basis for identifing new targets and biomarkers in therapeutic diagnosis.

Background: Centromere protein N (CENPN), located on chromosome 16q23.2, encodes vital nucleosome-associated complexes that are essential for dynamic assembly processes. CENPN plays a pivotal role in regulating cell proliferation and cell cycle progression by influencing mitotic events. Despite its potential importance, the precise functional role and regulatory mechanisms of CENPN in diverse malignancies remain largely unexplored. This study aimed to elucidate the role of CENPN in human cancers and evaluate its prognostic significance.

Methods: Investigate the role of CENPN in various malignancies, we leveraged data from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases. We employed a comprehensive suite of web platforms and software tools for data analysis, including R, Cytoscape, an integrated repository portal for tumor-immune system interactions (TISIDB), CBio Cancer Genomics Portal (cBioPortal), Search Tool for the Retrieval of Interaction Gene/Proteins (STRING), Gene Set Cancer Analysis (GSCALite), and a cancer single-cell state atlas (CancerSEA).

Results: The findings demonstrated that CENPN expression was elevated in the majority of cancer types and differentially expressed across molecular and immune subtypes. Functional enrichment analysis in multiple tumors also identified possible pathways of CENPN involvement in tumorigenesis. Its expression positively correlated with Th2 and Tcm cells in most cancers. It is also correlated with genetic markers of immunomodulators in various cancers.

Conclusions: Overall, CENPN expression is closely related to cancers and has the potential to act as a cancer biomarker.

Although previous studies have shown that preoperative pulmonary rehabilitation training may improve postoperative prognosis in patients with lung cancer, the literature included in the existing meta-analysis is highly heterogeneous and lacks effective subgroup analysis. Therefore, an updated meta-analysis is needed to integrate the latest published randomized controlled clinical trials (RCT). This updated analysis was performed to identify the clinical effects of preoperative pulmonary rehabilitation on physical rehabilitation (lung function, activity endurance, and dyspnea), psychological rehabilitation, quality of life, length of hospital stay, and postoperative pulmonary complications in patients with lung cancer. The PubMed, Embase, Cochrane Library, and Web of Science database were searched since inception up to March 2024. A random-effects model was used to pool data, and sensitivity and subgroup analyses were performed to explore the stability of outcomes and potential sources of heterogeneity. All analyses were conducted via Review Manager 5.4.1 and STATA 15.0. The final analysis included 11 RCTs with 1250 patients. The results of meta-analysis suggest that preoperative pulmonary rehabilitation can significantly improve the quality of life of patients with lung cancer after surgery (SMD: 0.16; 95% CI: 0.01, 0.32; P = 0.04) and significantly reduce the risk of postoperative pulmonary complications (PPCs) (RR: 0.39; 95% CI: 0.25, 0.60; P < 0.0001). The results of subgroup analysis suggested that the effect of combined preoperative and postoperative rehabilitation was significantly better than that of preoperative rehabilitation alone, and the effect of short-term preoperative pulmonary rehabilitation (≤ 3 weeks) was significantly better than that of long-term rehabilitation. Preoperative pulmonary rehabilitation for patients with lung cancer can significantly improve their postoperative quality of life and reduce postoperative complications, but factors such as intervention time and intervention method may affect the rehabilitation effect.