Explore the vast range of titles available.

Background Paclitaxel (PTX) serves as a first-line chemotherapeutic agent for the treatment of advanced non-small cell lung cancer (NSCLC). However, the emergence of drug resistance poses a significant threat to patient survival. The serine synthetic pathway (SSP) has been implicated in drug resistance across various cancers and is notably activated in NSCLC. Nevertheless, its role in PTX resistance remains poorly understood. Methods In this study, we investigated the influence of the SSP on PTX resistance in NSCLC and explored a novel combination therapeutic strategy involving PTX and anlotinib to reverse NSCLC drug resistance. Specifically, using integrated transcriptomic and metabolomic analyses along with in vitro and in vivo experimental approaches, we aimed to elucidate the regulatory role of activated SSP in PTX resistance and to determine whether the combination of anlotinib and PTX can overcome PTX resistance in NSCLC through modulation of the SSP. Results We found that SSP activation drives PTX resistance by promoting the proliferation of PTX-resistant NSCLC cells, increasing the expression and transport function of P-glycoprotein (P-gp), inducing epithelial-to-mesenchymal transition (EMT), and maintaining redox homeostasis. Anlotinib synergizes with PTX by suppressing SSP. This leads to attenuated glycolysis, disruption of the AKT/ERK proliferative signaling pathway, inhibition of P-gp expression and function, reversal of EMT, and redox imbalance, which subsequently elevates reactive oxygen species (ROS) levels and activates the mitochondrial apoptosis pathway, ultimately inducing apoptosis. Conclusion Collectively, our study demonstrates that anlotinib combined with PTX, via SSP inhibition, is a promising strategy for overcoming PTX resistance in NSCLC. Graphical abstract The combination of anlotinib and PTX effectively suppresses the SSP in A549/PTX cells. This suppression results in the following effects: (1) disruption of AKT/ERK proliferation signaling pathway transmission; (2) inhibition of P-gp expression and its efflux function; (3) blockade of the EMT process; (4) activation of the mitochondrial apoptosis pathway, thereby inducing cell apoptosis. Furthermore, the inhibition of SSP also exerts a certain degree of suppression on the glycolytic activity of A549/PTX cells.

Current non-invasive approaches for lung cancer (LC) detection exhibit inherent limitations in diagnostic accuracy, or inadequate clinical validation. Consequently, there exists an urgent unmet need for rigorously validated, non-invasive biomarkers exhibiting high sensitivity and specificity to enable the early detection of LC. We employed small RNA sequencing technology to detect microRNA (miRNA) expression in small extracellular vesicle (sEV) isolated from plasma samples of study participants. The collected samples were subjected to retrospective analysis. A diagnostic model was developed (n = 80) and validated (n = 52) to discriminate between non-malignant controls (NCs, comprising healthy individuals and benign lesions cases) and patients with LC (Stages I/II). Model performance was rigorously evaluated using several metrics, with the area under the curve (AUC) serving as the primary metric. The small RNA sequencing analysis of plasma sEV miRNA identified distinct expression signatures (14 differentially expressed sEV miRNAs) between NCs and LC samples. The diagnostic model with the best performance was constructed using hsa-miR-423-5p, hsa-miR-340-3p, hsa-miR-320b, hsa-miR-98-5p, hsa-miR-26a-5p, hsa-miR-193b-5p, hsa-miR-629-5p, and hsa-miR-92b-5p. The diagnostic model achieved an AUC of 0.956, a sensitivity of 94%, and a specificity of 93% in the training cohort and an AUC of 0.985, a sensitivity of 86%, and a specificity of 97% in the validation cohort. Our findings demonstrates that plasma sEV miRNA exhibits a highly discriminative biomarker for distinguishing NCs group from early malignant lesions, making it a promising tool for auxiliary detection of early-stage LC.

Abnormalities in trace elements and the incidence of oesophageal squamous cell carcinoma (ESCC) have been reported in China. Zinc ions (Zn ) are known to regulate DNA methylation by stabilizing methylase activity. However, the relationship between DNA methylation and Zn dysregulation in ESCC cells remains unclear. In this study, we examined changes in the biological behavior of ESCC cells treated with or without Zn . Biological behaviour changes in ESCC cells treated with or without Zn were analysed. Differences in the methylome and transcriptome of Zn -treated cells were determined by reduced representation bisulfite sequencing and RNA sequencing. An MTT cell viability assay was used to evaluate the cytotoxicity of cisplatin combined with Zn . Zn can inhibit the malignant biological behaviour of ESCC cells. CpG methylation levels of promoter regions were decreased after Zn treatment in both ESCC and control cells. The degree of DNA methylation of genes encoding the metal ion-binding factors MT1E, MT1H and MT1X was significantly decreased, but their RNA expression levels were significantly increased after Zn treatment. Zn may enhance the expression of metallothioneins (MTs) via positive feedback through methylation regulation mechanisms. assays showed that the IC50 of Zn in ESCC cells was significantly lower than that in cells treated with cisplatin alone. In addition, ECa patients with high MT1E expression had a better prognosis. Zn can reduce the methylation level and malignant biological behaviour of ESCC cells. The combination of Zn and cisplatin increases ESCC inhibition. Further study of MTs as biomarkers and targets in ESCC is warranted.

G protein-coupled estrogen receptor (GPER) significantly influences metabolic regulation by engaging multiple signaling pathways that affect overall metabolic health. Its structure and signaling mechanisms drive its diverse roles. Our team and others have successfully demonstrated that GPER modulates nutrient metabolism, spanning glucose, protein, and lipid metabolism, while also contributing to vitamin and mineral metabolism. Studies have linked GPER to metabolic disorders, including type 2 diabetes, nonalcoholic fatty liver disease, metabolic syndrome, and cardiovascular diseases, as well as thyroid disorders, highlighting its wide-reaching metabolic impact. GPER holds promise for energy balance and weight management by regulating energy expenditure and thermogenesis. Moreover, it appears to influence the metabolism of cancer cells during tumor progression. Rapid advancements in GPER agonist and antagonist research have highlighted the therapeutic potential of GPER agonists for treating metabolic diseases. Further investigations into GPER biology, mechanisms, and clinical applications will support novel therapeutic strategies, establishing GPER as a key target in metabolic research and treatment.

Background and purpose Ubiquitination modifications can affect hepatocellular carcinoma (HCC) progression through various signaling pathways. However, no significant results have been observed regarding protein ubiquitination in HCC’s therapeutic transformation. This study aimed to explore the research areas related to ubiquitination and HCC from a bibliometric perspective. Methods Articles and reviews on HCC and ubiquitination published between 2000 and 2023 were obtained from the Web of Science Core Collection (WOSCC). CiteSpace, VOSviewer, and R-bibliometrix were used for the bibliometric and visualization analyses. Results Altogether, 358 papers on ubiquitination and HCC were extracted from the WOSCC. Over 24 years, the number of publications has increased. Since the beginning of 2019, studies related to this topic have increased significantly, indicating that the role of ubiquitination modification in HCC is currently popular. China is the leading country in this field with the largest number of publications. The Chinese Academy of Sciences is one of the most influential institutions. Qiao, Yongxia, and Zhang Jie are highly productive authors with major achievements. The journal Cell Death & Disease had the highest number of publications, and the most highly cited journal was Oncogene . The highest citation burst intensity was Sung (2021). In the keyword strategy map, “cancer antigens” are popular keywords in HCC and ubiquitination research. Conclusion A comprehensive visual analysis of ubiquitination and HCC research was conducted using bibliometric methods, showing the publications and popular topics in this field over the past two decades, thus providing references for the future direction of ubiquitination and HCC research.

A variety of abnormal epithelial cells and immature and mature immune cells in thymic epithelial tumors (TETs) affect histopathological features, the degree of malignancy, and the response to treatment. Here, gene expression, trajectory inference, and T cell antigen receptor (TCR)‐based lineage tracking are profiled in TETs at single‐cell resolution. An original subpopulation of KRT14+ progenitor cells with a spindle cell phenotype is shown. An abnormal infiltration of immature T cells with a TCR hyper‐rearrangement state is revealed, due to the lack of CCL21+ medullary epithelial cells. For thymic carcinoma, the novel biomarkers of MSLN, CCL20, and SLC1A5 are identified and observed an elevated expression of LAG3 and HAVCR2 in malignant tumorn‐infiltrating mature T cells. These common features based on the single‐cell populations may inform pathological reclassification of TETs. Meanwhile, it is found that macrophages (MACs) attract thymic tumor cells through the LGALS9‐SLC1A5 axis, providing them with glutamine to elicit metabolic reprogramming. This MAC‐based metabolic pattern can promote malignancy progression. Additionally, an interactive immune environment in TETs is identified that correlates with the infiltration of abnormal FOXI1+ CFTR− ionocytes. Collectively, the data broaden the knowledge of TET cellular ecosystems, providing a basis for tackling histopathological diagnosis and related treatment. A variety of abnormal epithelial cells and immature and mature immune cells in thymic epithelial tumors (TETs) affect histopathological features. Through single‐cell resolution perspective and in vitro organoid analysis, the TETs cell ecosystem is deciphered, which provides a basis for tackling histopathological diagnosis and related treatment.

The activation of nuclear factor erythroid 2–related factor 2 (NRF2) has been observed in various cancers. Yet its exact contribution to the development of head and neck squamous cell carcinoma (HNSCC) remains undetermined. We previously found that NRF2 signaling is critical for the differentiation of squamous basal progenitor cells, while disruption of NRF2 causes basal cell hyperplasia. In this study, we revealed a correlation between elevated NRF2 activity and poor outcomes in HNSCC patients. We demonstrated that NRF2 facilitates tumor proliferation, migration, and invasion, as evidenced by both in vitro and in vivo studies. Significantly, NRF2 augments the expression of the antioxidant enzyme GPX2, thereby enhancing the proliferative, migratory, and invasive properties of HNSCC cells. Activation of GPX2 is critical for sustaining cancer stem cells (CSCs) by up-regulating NOTCH3, a key driver of cancer progression. These results elucidate that NRF2 regulates HNSCC progression through the NRF2-GPX2-NOTCH3 axis. Our findings proposed that pharmacological targeting of the NRF2-GPX2-NOTCH3 axis could be a potential therapeutic approach against HNSCC.

This study aimed to construct a signature of N 6 -methyladenosine (m6A) regulator-related genes that could be used for the prognosis of head and neck squamous cell carcinoma (HNSCC) and to clarify the molecular and immune characteristics and benefits of immune checkpoint inhibitor (ICI) therapy using the prognostic signature to define the subgroups of HNSCC. This study showed that eighteen m6A regulators were abnormally expressed in the Cancer Genome Atlas (TCGA) HNSCC tissues compared with those in normal tissues. We constructed a signature of 12 m6A regulator-related genes using the Cox risk model, combined with the least absolute shrinkage and selection operator (Lasso) variable screening algorithm. Based on the median of the signature risk score, the patients were divided into high- and low-risk groups. The Kaplan–Meier survival analyses showed that patients with high-risk scores demonstrated poorer overall survival (OS) than those with low-risk scores based on TCGA-HNSCC data ( p < 0.001). The OS of high-risk patients was significantly worse than that of low-risk patients in the GSE65858 ( p < 0.001) and International Cancer Genome Consortium (ICGC) oral cancer cohorts ( p = 0.0089). Furthermore, immune infiltration analyses showed that 8 types of immune cell infiltration showed highly significant differences between the two risk groups ( p < 0.001). In the Imvigor210CoreBiologies dataset of patients who received ICIs, the objective response rate (ORR) of the low-risk group (32%) was significantly higher than that of the high-risk group (13%). Additionally, patients in the high-risk group presented with a more significant adverse OS than that of the low-risk group ( p = 0.00032). GSE78220 also showed that the ORR of the low-risk group (64%) was higher than that of the high-risk group (43%) and the OS of low-risk patients was better than that of high-risk patients ( p = 0.0064). The constructed prognostic signature, based on m6A regulator-related genes, could be used to effectively distinguish between prognoses for HNSCC patients. The prognostic signature was found to be related to the immune cell infiltration of HNSCC; it might help predict the responses and prognoses of ICIs during treatment.

To improve personalized diagnosis and prognosis for oral squamous cell carcinoma (OSCC) by identification of hub methylated‐CpG sites and associated genes, weighted gene comethylation network analysis (WGCNA) was performed to examine and identify hub modules and CpG sites correlated with OSCC. Here, WGCNA modeling yielded blue and brown comethylation modules that were significantly associated with OSCC status. Following screening of the differentially expressed genes (DEGs) from gene expression microarrays and differentially methylated‐CpG sites (DCGs), integrated multiomics analysis of the DEGs, DCGs, and hub CpG sites from the modules was performed to investigate their correlations. Expression levels of 16 CpG sites‐associated genes were negatively correlated with methylation patterns of promoter. Moreover, Kaplan‐Meier survival analysis of the hub CpG sites and associated genes was carried out using 2 public databases, MethSurv and GEPIA. Only 5 genes, ACTA1, ACTN2, OSR1, SYNGR1, and ZNF677, had significant overall survival using GEPIA. Hypermethylated‐CpG sites ACTN2‐cg21376883 and OSR1‐cg06509239 were found to be associated with poor survival by MethSurv. Methylation status of specific site and expression levels of associated genes were determined using clinical samples by quantitative methylation‐specific PCR and real‐time PCR. Pearson's correlation analysis showed that methylation levels of cg06509239 and cg18335068 were negatively related to OSR1 and ZNF677 expression levels, respectively. Our classification schema using multiomics analysis represents a screening framework for identification of hub CpG sites and associated genes. Construction of comethylation network associated with oral squamous cell carcinoma status by WGCNA. Dendrogram of consensus module eigengenes obtained by WGCNA on the consensus correlation. Seven modules were generated after merging according to the correlation of modules.

The subtle imaging features of thymic epithelial tumors (TETs), which comprise multiple pathological subtypes of thymoma and thymic carcinoma, are of great significance for the identification of high-risk patients. Finding the radiomics features related to the immunohistochemical markers of TETs may provide a non-invasive method for the construction of a prediction model. This retrospective study analyzed non-enhanced computed tomography (NECT) images of 307 patients with TETs from two institutions. The radiomic features were extracted, clustered, and used to develop the models with machine learning algorithms. In general, the radiomics of TET patients were profiled and clustered into three clusters, which showed differences in correlation between clinicopathological characteristics, including histological type, Masaoka stage, and immunohistochemical results. Moreover, the “original-shape-flatness” and “wavelet-LHL-first-order-Median” were the most strongly correlated with CD117 and TDT expression, and the combined model of the two demonstrated predictive efficacy for CD117/TDT expression and risk groups in training and validation cohorts. This study highlights that radiomics and biomarker-associated features can serve as a non-invasive predictive biomarker for TET patients.