Cancer stem cells (CSCs) are crucial for lung adenocarcinoma (LUAD). This study investigates tumor stem cell gene signatures in LUAD using single-cell RNA sequencing (scRNA-seq) and bulk RNA sequencing (RNA-seq), aiming to develop a prognostic tumor stem cell marker signature (TSCMS) model. LUAD scRNA-seq and RNA-seq data were analyzed. CytoTRACE software quantified the stemness score of tumor-derived epithelial cell clusters. Gene Set Variation Analysis (GSVA) identified potential biological functions in different clusters. The TSCMS model was constructed using Lasso-Cox regression, and its prognostic value was assessed through Kaplan–Meier, Cox regression, and receiver-operating characteristic (ROC) curve analyses. Immune infiltration was evaluated using the Cibersortx algorithm, and drug response prediction was performed using the pRRophetic package. TAF10 functional investigations in LUAD cells involved bioinformatics analysis, qRT-PCR, Western blot, immunohistochemistry, and assays for cell proliferation. Seven distinct cell clusters were identified by CytoTRACE, with epithelial cell cluster 1 (Epi_C1) showing the highest stemness potential. The TSCMS model included 49 tumor stemness-related genes; high-risk patients exhibited lower immune and ESTIMATE scores and increased tumor purity. Significant differences in immune landscapes and chemotherapy sensitivity were observed between risk groups. TAF10 positively correlated with RNA expression-based stemness scores in various tumors, including LUAD. It was over-expressed in LUAD cell lines and clinical tumor tissues, with high expression linked to poor prognosis. Silencing TAF10 inhibited LUAD cell proliferation and tumor sphere formation. This study demonstrates the TSCMS model's prognostic value in LUAD, reveals insights into immune infiltration and therapeutic response, and identifies TAF10 as a potential therapeutic target.

Nasopharyngeal carcinoma (NPC) presents a substantial clinical challenge due to the limited understanding of its genetic underpinnings. Here we conduct the largest scale whole-exome sequencing association study of NPC to date, encompassing 6,969 NPC cases and 7,100 controls. We unveil 3 germline genetic variants linked to NPC susceptibility: a common rs2276868 in RPL14 , a rare rs5361 in SELE , and a common rs1050462 in HLA-B . We also underscore the critical impact of rare genetic variants on NPC heritability and introduce a refined composite polygenic risk score (rcPRS), which outperforms existing models in predicting NPC risk. Importantly, we reveal that the polygenic risk for NPC is mediated by EBV infection status. Utilizing a comprehensive multiomics approach that integrates both bulk-transcriptomic ( n = 356) and single-cell RNA sequencing ( n = 56) data with experimental validations, we demonstrate that the RPL14 variant modulates the EBV life cycle and NPC pathogenesis. Furthermore, our data indicate that the SELE variant contributes to modifying endothelial cell function, thereby facilitating NPC progression. Collectively, our study provides crucial insights into the intricate genetic architecture of NPC, spotlighting the vital interplay between genetic variations and tumor microenvironment components, including EBV and endothelial cells, in predisposing to NPC. This study opens new avenues for advancements in personalized risk assessments, early diagnosis, and targeted therapies for NPC.

Background: Small cell lung cancer (SCLC) is an aggressive malignancy with limited treatment options and poor prognosis, underscoring the need for new therapeutic agents.Methods: A library of 640 natural products was screened for anti-proliferative activity in SCLC cells. The effects of Cepharanthine (CE) on SCLC cells were assessed in vitro and in vivo. Network pharmacology and RNA sequencing (RNA-seq) were used to elucidate the molecular mechanisms. Pathway enrichment analysis was performed using Gene Set Enrichment Analysis (GSEA) with Hallmark and Reactome gene sets. Protein-protein interaction (PPI) networks, along with the Cytoscape cytoHubba plugin, were used to identify key hub genes. RT-PCR and Western blotting were employed to validate mRNA and protein expression. Molecular docking studies assessed the binding affinity of CE to potential targets. Bioinformatics analyses, including expression profiling, prognostic evaluation, and loss-of-function studies, were used to explore the role of specific genes in SCLC.Results: CE was identified as a promising SCLC inhibitor. In vitro, CE significantly inhibited SCLC cell proliferation, colony formation, migration, and invasion, while promoting apoptosis. In vivo, CE treatment notably reduced tumor volume in xenograft models. Network pharmacology identified 60 potential target genes, with enrichment analysis indicating their involvement in cholesterol metabolism regulation. RNA-seq and experimental validation further confirmed that CE inhibits cholesterol synthesis in SCLC cells by downregulating key enzymes, including HMGCR, HMGCS1, IDI1, FDFT1, and SQLE. Molecular docking studies confirmed the binding of CE to these enzymes. Additionally, these enzymes were found to be highly expressed in SCLC cells, with elevated levels of HMGCS1, HMGCR, and IDI1 correlating with poor prognosis. Functional assays revealed that silencing these genes significantly suppressed SCLC cell proliferation.Conclusion: This study identifies CE as a potential therapeutic agent for SCLC, acting through the suppression of cholesterol synthesis, and uncovers novel therapeutic targets for the treatment of this aggressive cancer.

Intrahepatic Cholangiocarcinoma (ICC) is a highly aggressive malignancy with limited treatment options. Identifying novel therapeutic agents for ICC is crucial. Numerous natural compounds have demonstrated remarkable anti-tumor activities and can enhance the efficacy of chemotherapy. Thus, our study aimed to screen natural compounds for their anti-ICC effects. A total of 640 natural compounds were screened using a cell viability assay to identify potential compounds that could inhibit the proliferation of ICC cells. The anti-ICC effects of Lycorine Hydrochloride (LY) were confirmed through cell proliferation, colony formation, cell cycle, migration, and invasion assays, as well as in xenograft models. Bioinformatics analyses and validation experiments (Quantitative real-time PCR, Western blot, and immunostaining assays) were utilized to investigate the roles of genes (SQLE, FDFT1, and PTPN11) in ICC. RNA sequencing and immunofluorescence staining were performed to elucidate underlying molecular mechanisms. LY was identified as a potential ICC inhibitor, exhibiting anti-ICC effects both in vitro and in vivo. Mechanistically, LY inhibited cholesterol synthesis in tumor cells by down-regulating the expression of SQLE and FDFT1. The knockdown of SQLE or FDFT1 significantly inhibited ICC cell proliferation and colony formation. RNA sequencing confirmed that inhibition of FDFT1 suppressed the cholesterol biosynthesis pathway, while SQLE inhibition affected specific oncogenic pathways. Additionally, immunofluorescence staining revealed that down-regulation of SQLE reduced PTPN11 expression and inhibited its nuclear translocation. Furthermore, pharmacological inhibition of SQLE and FDFT1 by LY significantly enhanced sensitivity to several common chemotherapeutic drugs for ICC. Notably, the combination of LY and Gemcitabine (GEM) displayed the most potent synergistic anti-tumor effect across various tumor types. These findings identify Lycorine Hydrochloride as a promising treatment alternative for ICC and propose a novel combination strategy (LY + GEM) for treating multiple solid tumors.

Introduction：Nasopharyngeal carcinoma (NPC) is mostly associated with EBV infection, which often leads to poor prognosis and a high mortality rate of NPC patients due to the high susceptibility of NPC cells to local infiltration of lymph nodes and distant metastasis. Methods： This study aimed to evaluate the diagnostic value of serum BNLF2b for nasopharyngeal carcinoma. A total of 318 patients (male-to-female ratio: 200:118) were selected to attend the Zhongshan People's Hospital from December 2021 to May 2023, including 152 nasopharyngeal carcinoma patients, 71 healthy subjects in the physical examination center and 95 nasopharyngitis patients.Elbow venous blood was collected from all of patients, and the content of BNLF2b was determined after quantitative serum extraction.The diagnostic value of serum BNLF2b for nasopharyngeal carcinoma was analyzed using the subject's work characteristics (ROC) curve, and logistic two-factor regression analysis was used to predict the ROC curves of the risk factors for the development of nasopharyngeal carcinoma by the combined diagnosis of multiple indicators. Results：we found that serum BNLF2b was significantly and positively correlated with EBV-DNA, nasopharyngeal carcinoma stage, IL-6, and IL-10. Serum BNLF2b was highly efficient in the diagnosis of nasopharyngeal cancer, with an AUC of 0.92, a sensitivity of 99%, and a specificity of 93%. In addition, in the diagnosis of early nasopharyngeal carcinoma, serum BNLF2 had an AUC of 0.97, a sensitivity of 100%, and a specificity of 97%. Conclusion： BNLF2b is a feasible new serum biomarker for diagnosis of nasopharyngeal carcinoma.