Gastric cancer (GC) is a leading gastrointestinal malignancy carrying a poor prognosis. Lymphangiogenesis (LYM) refers to the process of forming new lymphatic vessels. This process facilitates tumor metastasis and represents a promising therapeutic target in GC management. However, the exact mechanisms of LYM in GC remain incompletely understood.

SMARCA4-deficient undifferentiated tumor (SMARCA4-UT) has emerged as a rare subtype of thoracic tumor, whose prognosis is unfavorable and for which standard therapeutic regimen is presently unavailable.

The success of tyrosine kinase inhibtors in the neoadjuvant and adjuvant setting provides a rationale for exploring selpercatinib in the perioperative setting to improve patient outcomes in early-stage lung cancer. However, selpercatinib is currently only approved as first-line treatment for advanced rearrangement during transfection (RET) fusion-positive non-small cell lung cancer (NSCLC), limiting its use and potential benefit for earlier stage patients. Hence, this case report explores selpercatinib's potential use in early-stage disease to address this treatment gap and improve patient outcomes.

Ovarian metastasis from anaplastic lymphoma kinase (ALK)-positive lung adenocarcinoma is exceedingly rare. Reporting such cases is vital for understanding its clinical management.

Myasthenia gravis (MG), an autoimmune condition known for impairing neuromuscular signaling, has increasingly been implicated in broader neurological dysfunctions. Recent studies point toward a possible connection between autoimmune and neurodegenerative processes. However, whether MG contributes causally to the onset of major neurodegenerative disorders such as Alzheimer disease (AD), Parkinson disease (PD), and amyotrophic lateral sclerosis (ALS) remains unclear. This study utilizes Mendelian randomization (MR) to explore the potential causal influence of MG on these disorders from a genetic standpoint. A univariable Mendelian randomization (UVMR) framework was employed using summary-level data from genome-wide association studies (GWAS) to evaluate the effect of MG on the risk of AD, PD, and ALS. To confirm the robustness of the association between MG and AD, 2 independent AD GWAS datasets were incorporated for external replication, followed by a meta-analysis to combine the evidence. Additionally, multivariable Mendelian randomization (MVMR) was conducted to adjust for smoking behavior as a potential confounding factor. The UVMR analysis revealed a statistically significant causal relationship between MG and increased susceptibility to AD (odds ratio (OR): 1.037; 95% confidence interval (CI): 1.007-1.068; P = .016). No significant causal effects were observed for PD (OR: 1.019; 95% CI: 0.964-1.077; P = .509) or ALS (OR: 1.055; 95% CI: 0.977-1.140; P = .171). The association between MG and AD was consistently validated in 2 independent datasets (ieu-a-297: OR = 1.084; 95% CI: 1.017-1.156; P = .013; ieu-b-2: OR = 1.054; 95% CI: 1.006-1.104; P = .027). Meta-analysis reinforced the evidence supporting MG as a risk factor for AD (OR: 1.047; 95% CI: 1.023-1.072; P < .001). Furthermore, MVMR adjusting for smoking confirmed that MG independently contributes to AD risk (OR: 1.037; 95% CI: 1.006-1.069; P = .020). This study provides robust genetic evidence suggesting that MG is a causal and independent risk factor for AD. These findings highlight a novel link between autoimmunity and neurodegeneration, offering new directions for mechanistic and therapeutic research.

This study aimed to investigate a causal association between Klotho levels and the risk of B-cell lymphoma using a Mendelian randomization (MR) approach. We sought to determine if α-Klotho levels are causally linked to various subtypes of B-cell lymphoma, including diffuse large B-cell lymphoma, follicular lymphoma, Hodgkin lymphoma, and non-Hodgkin lymphoma. We obtained GWAS data for B-cell lymphomas from the FINN Large Cohort in the IEU database and α-Klotho levels from a meta-analysis of GWAS data. The primary analysis employed the inverse-variance weighted method, while sensitivity analyses utilized weighted median, MR-Egger, and weighted mode methods to validate results. Heterogeneity and pleiotropy of genetic instruments were assessed using leave-one-out sensitivity tests, the MR pleiotropy residual sum and outlier test (MR-PRESSO), and Cochran Q test. Our analysis revealed no significant associations between α-Klotho levels and any subtype of B-cell lymphoma using inverse-variance weighted (IVW). The odds ratios and 95% confidence intervals indicated no significant relationship for diffuse large B-cell lymphoma, follicular lymphoma, Hodgkin lymphoma, or unspecified non-Hodgkin lymphoma. Heterogeneity tests and sensitivity analyses supported the robustness of these findings. Our comprehensive MR analysis suggests no causal relationship exists between Klotho levels and the risk of developing B-cell lymphomas.

To investigate the causal relationship between follistatin (FST) levels and endocrine diseases such as polycystic ovary syndrome (PCOS), type 2 diabetes (T2DM), obesity, and osteoporosis (OP) using a 2-sample Mendelian randomization (MR) analysis. Instrumental variables closely associated with FST levels were obtained from large-scale genome-wide association study data in the IEU database. Summary-level data for 4 endocrine diseases were sourced from the latest version of the FinnGen database. Our primary method for MR analysis was the inverse-variance weighted (IVW) method, supplemented by the MR-Egger and Weighted Median methods. We conducted a series of sensitivity tests to assess the reliability of our MR results. The IVW analysis revealed a significant causal relationship between elevated levels of FST and both PCOS (odds ratio [OR] = 1.129, 95% confidence interval [CI]: 1.042-1.224, P = .003) and T2DM (OR = 1.103, 95% CI: 1.02-1.187, P = .01). However, the IVW model did not indicate a causal connection between FST levels and either OP (OR = 1.061, 95% CI: 0.909-1.238, P = .452) or obesity (OR = 1.082, 95% CI: 0.983-1.192, P = .108). The reverse MR analysis results indicated a causative association between T2DM (OR = 1.047, 95% CI: 1.006-1.089, P = .023) and an elevation in FST levels, as well as a causal link between OP (OR = 0.889, 95% CI: 0.804-0.982, P = .021) and a reduction in FST levels. There is no direct causality between PCOS (OR = 0.925, 95% CI: 0.778-1.098, P = .372), obesity (OR = 1.035, 95% CI: 0.968-1.107, P = .312), and FST levels. In addition, our sensitivity tests, which included a pleiotropy test, heterogeneity test, and "leave-one-out" analysis, consistently confirmed the reliability of our results. Genetically predicted high FST levels are causally associated with increased risks of PCOS and T2DM, indicating a potential role in endocrine disease pathogenesis. Moreover, reverse MR analysis revealed a significant causal link between OP and decreased FST levels, suggesting that FST may serve as a promising biomarker or therapeutic target in bone metabolism.

Neurofibromatosis type 1 (NF1), an autosomal dominant genetic disorder, exhibits a high prevalence across populations. The quintessential clinical manifestations of NF1 encompass a spectrum of features, including neurofibromas, café-au-lait macules (CALMs), skinfold freckling, Lisch nodules, and an array of central nervous system tumors. The pathogenesis of NF1 is intricately tied to mutations within the NF1 gene, situated on chromosome 17q11.2. This gene encodes the neurofibromin protein, whose functional loss leads to deregulated cell growth, thereby fostering an environment conducive to tumorigenesis.

This study investigates the expression and clinical significance of N-acetylglucosaminyltransferase V (MGAT5) in colon adenocarcinoma (COAD) using bioinformatics methods. The mRNA and protein expression of MGAT5 in COAD tissues and the expression of MGAT5 in various cell lines of COAD were analyzed using the databases. The relationship between MGAT5 expression and clinical pathological features of COAD was analyzed by UALCAN. The relationship between MGAT5 and cellular immune infiltration in COAD was analyzed in TIMER database; the relationship between MGAT5 and prognosis of COAD patients was analyzed in GEPIA. The co-expression genes of MGAT5 in COAD were obtained on Linkedomics and imported into Metascape for pathway enrichment analysis. We predicted and constructed MGAT5 protein-protein interaction network in human samples using the STRING database. Compared with normal colon tissues, MGAT5 exhibited high expression in both mRNA and protein levels, and MGAT5 was also overexpressed in most COAD cell lines. There were significant differences in expression level of MGAT5 in different pathological stages of COAD. MGAT5 was positively correlated with the infiltration of CD8 + T cells, CD4 + T cells, macrophages, neutrophils and dendritic cells. The disease-free survival of MGAT5 low expression group was better than that of MGAT5 high expression group. The genes co-expressed with MGAT5 were predominantly implicated in the Notch signaling pathway and N-glycan biosynthesis processes. MGAT5 was significantly upregulated in COAD and correlated with poor prognosis and immune infiltration in COAD. This suggested that MGAT5 may serve as a valuable biomarker for clinical prognosis and a potential target for immunotherapy in COAD.

The heterogeneity of pancreatic adenocarcinoma (PAAD) tumors is complex. The purpose of this work was to use immunologic signature gene sets (ISGS) activity alterations to identify subtypes of PAAD and to develop valid prognostic indicators. We discovered tumor-related differentially expressed gene sets and their associated subtypes by analyzing changes in ISGS activity via the cancer genome Atlas and the genotype-tissue expression datasets. To evaluate the relationship between these subtypes and clinical characteristics, the immunological microenvironment, and tumor immune dysfunction and exclusion, we conducted survival studies. Furthermore, we identified subtype-specific gene sets and developed a prognostic risk score (RS) model and a corresponding nomogram. The robustness and generalizability of the RS model were validated using the gene expression omnibus dataset. Additionally, differences in drug sensitivity and tumor mutation burden were compared between risk groups. On the basis of variations in ISGS activity, 2 subtypes of PAAD were distinguished. The prognosis is worse for subtype 1 patients, and there is no statistically significant difference between the clinicopathologic characteristics of the 2 subtypes. However, subtype 1 patients do not respond well to immunotherapy, and the immunological microenvironment varies significantly across subtypes. Additionally, patients were assigned to distinct risk groups by a prognostic RS model based on differentially expressed genes linked to both subtypes. Individuals belonging to distinct risk categories exhibited varying degrees of medication sensitivity; high-risk patients also had shorter survival periods and greater tumor mutation burden. For patients with pancreatic cancer, nomograms that include RS and clinicopathologic variables are may provide useful tools. Our research used the ISGS to identify subtypes of PAAD and created prognostic RS models. Through the integration of the RS and clinicopathological parameters into nomograms, prognostic prediction may be reinforced, and may provide new perspectives for future personalized treatment strategies.

Prostate cancer (PCa) ranks among the most prevalent malignancies worldwide. Within the tumor microenvironment (TME), cancer-associated fibroblasts (CAFs) play a crucial role in influencing tumor evolution and progression. To elucidate their prognostic significance, we extracted and integrated PCa data from The Cancer Genome Atlas and the GSE70768, GSE70769, and GSE116918 datasets. Differentially expressed CAF-related genes between normal and tumor tissues were identified, and their associations with CAF subtypes and clinicopathological characteristics were explored through Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses. Based on these features, we constructed a CAF-related prognostic model using multivariate Cox and least absolute shrinkage and selection operator regression analyses. A 9-gene signature (LMCD1, CXCL2, UNC5B, THBS2, JAM3, PIGR, SCUBE2, SRD5A2, and PCGEM1) was identified to generate a CAFs score for predicting biochemical recurrence risk. Further analyses of the TME, genetic mutations, and drug sensitivity revealed that this signature was closely associated with tumor immunity and treatment response. Collectively, this model highlights the pivotal role of CAFs in shaping the TME and provides novel insights for prognostic prediction and therapeutic strategies in PCa.

To systematically evaluate the efficacy and safety of anlotinib plus epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) in the treatment of advanced non-small cell lung cancer (NSCLC) with EGFR mutations.

Colorectal cancer (CRC), as a common malignant tumor of digestive tract, is a serious threat to people's life and health. At present, the commonly used therapeutic drugs have the characteristics of large effect and easy resistance, forcing us to find highly effective and low toxicity therapeutic drugs. Xiaotan Sanjie Fang (XTSJF) has achieved good clinical efficacy as an empirical prescription for the treatment of gastrointestinal tumors in Traditional Chinese Medicine, but its specific composition and molecular mechanism are still unclear. We therefore investigated the potential mechanism of action of XTSJF in the treatment of CRC using network pharmacology and molecular docking approaches. First we collected components and targets of XTSJF from public databases (TCMSP and BATMAN) and CRC targets from disease databases (Genecards and OMIM); then we obtained cross-targets of XTSJF and CRC by Venn diagram mapping. Continued enrichment analysis of cross-targets using Cytoscape and R software identified PI3K/AKT as a possible critical signaling pathway. Finally, EGFR, JUN, RELA, STAT3, and TP53 were identified as key targets by topological analysis and molecular docking, and 5 key genes were further validated by gene and protein expression analysis of key targets. The hairstyle of these results provides a direction for in-depth studies of XTSJF in CRC.

Thyroid cancer (THCA) patients may be affected by circadian rhythm disorder (CRD). Since melatonin (MT) has both antitumor and regulatory effects on CRD, this study aimed to evaluate the functional role and potential mechanism of action of MT as a therapeutic agent against THCA and regulation of CRD. The intersection between differentially expressed genes of THCA and circadian rhythm-related genes (CRGs) was identified and hub genes were further screened to construct a prognostic model. The relationship between the expression of THCA/CRGs and immune infiltration was evaluated in the low-risk and high-risk groups. The molecular targets of MT acting on THCA/CRGs were screened and topological analysis was performed. Multivariate Cox regression analysis identified 3 core genes, COL18A1, DPP4, and APOE, to construct the prognostic model. The clinical information analysis and immunohistochemical analysis of core genes showed that in THCA, COL18A1 was downregulated (P < .05), while DPP4 and APOE were upregulated (P < .05). Subgroup analysis showed that COL18A1, DPP4, and APOE may be associated with different factors in different subgroups. The results of immune infiltration analysis showed that compared with the low-risk group, the high-risk group had higher stromal score (P < .001), lower immune score (P < .001), and ESTIMATE score (P < .001). Additionally, the expression of THCA/CRGs was closely associated with the infiltration of various immune cells. A total of 25 molecular targets of MT against THCA/CRD were identified by online databases. Topological analysis identified 6 molecular targets with the best performance, including LGALS3, MMP9, CTSB, DPP4, PPARG, and ALB, with binding energy <-5 kcal/mol for molecular docking with MT. The prediction model constructed in this study shows good diagnostic and prognostic performance. In addition, this study revealed the pharmacological targets of MT against THCA/CRD, providing a potential theoretical basis for exploring new clinical treatment options.

Hepatocellular carcinoma (HCC), a common malignant primary tumor, is usually diagnosed in advanced stages. Studies increasingly indicate the involvement of long noncoding RNAs (lncRNAs) in HCC development. Disulfidptosis, a recently discovered form of programmed cell death, involves abnormal disulfide accumulation within cells. This study involved the associations between disulfidptosis-related lncRNAs and HCC prognosis. Multivariate Cox regression and the least absolute shrinkage and selection operator were jointly employed to develop the risk prediction model. Diagnostic accuracy was assessed with Kaplan-Meier survival and receiver operating characteristics analysis. In addition, we investigated the risk models' relationships with immune function, somatic mutations, and drug sensitivity. We developed a signature based on 3 lncRNAs associated with disulfidptosis. Patients in the high-risk group had poorer overall survival than those in the low-risk group. Time-dependent receiver operating characteristics analysis showed the risk score achieved AUCs of 0.756 (1 year), 0.695 (3 years), and 0.701 (5 years). In addition, we constructed a nomogram that predicting 5-year survival in patients with HCC, which may help clinicians predict prognosis from a new perspective. Furthermore, we observed significant differences in immune function, tumor mutational burden, and drug sensitivity between the high-risk and low-risk groups. The proposed 3-disulfidptosis-related lncRNAs-based signature is a promising biomarker for predicting clinical outcomes of HCC.

Non-small cell lung cancer (NSCLC) is considered a major contributor to cancer-related death rates worldwide, chiefly owing to late diagnosis, occurrence of metastasis, and treatment resistance. Growing evidence underscores the impact of long non-coding RNAs (lncRNAs) on NSCLC progression. These lncRNAs have been demonstrated to influence cell proliferation, apoptosis, epithelial-mesenchymal transition (EMT), and drug resistance, contributing to cancer development and therapeutic failure. Concurrently, natural products and nutraceuticals are gaining attention for their anticancer properties, particularly in modulating signaling pathways involved in tumorigenesis and drug resistance. Compounds like curcumin, resveratrol, and epigallocatechin gallate have been shown to regulate oncogenic lncRNAs, inhibiting metastasis and reversing chemoresistance. Additionally, natural products upregulate tumor-suppressive lncRNAs, restoring cell cycle control and apoptosis. This review provides an in-depth analysis of the etiological significance of lncRNAs in NSCLC, with a particular emphasis on their contribution to tumorigenesis, metastasis, and therapeutic resistance. In addition, it explores the potential of natural products to modulate lncRNA expression, highlighting their efficacy in overcoming drug resistance and enhancing the therapeutic response. By elucidating the dynamic molecular cross-talk between lncRNAs and natural products, this review also aims to identify novel therapeutic strategies and potential biomarkers for the diagnosis and treatment of NSCLC.

Lung cancer currently holds the highest global incidence and mortality rates among malignant tumors, with lung adenocarcinoma being the most prevalent and deadly subtype. Chemotherapy and targeted therapy remain the standard treatments for lung adenocarcinoma, but tumor resistance continues to be a significant clinical challenge. In this study, we identified that the long non-coding RNA actin filament associated protein 1 antisense RNA 1 (AFAP1-AS1), which is highly expressed in lung adenocarcinoma, regulates RNA alternative splicing by recruiting splicing factors such as serine and arginine rich splicing factor 1 and 3 (SRSF1 and SRSF3), promoting their liquid-liquid phase separation. Among the affected splicing events, the exon 7 skipping of the key regulatory gene AXIN2, involved in the Wnt/β-catenin signaling pathway, is most notably regulated by AFAP1-AS1, resulting in the translation of a truncated AXIN2 isoform (AXIN2-S). This isoform facilitates the accumulation of β-catenin in the nucleus and the persistent activation of Wnt/β-catenin signaling pathway, ultimately contributing to drug resistance in lung adenocarcinoma. Our work uncovers a novel function of AFAP1-AS1 in regulating RNA alternative splicing through the modulation of splicing factors phase separation. This mechanism highlights an unrecognized pathway by which AFAP1-AS1 promotes drug resistance in lung adenocarcinoma, suggesting that AFAP1-AS1 and its regulated splicing events may serve as potential biomarkers or therapeutic targets for the treatment of lung adenocarcinoma.

Disruption of circadian rhythm (DCR) has been connected with breast cancer (BC) susceptibility; whereas it is unclear whether status of key clock genes could be used in predicting BC prognosis, tumor immune microenvironment, and immunotherapy responses.

Gastric cancer (GC) is a highly aggressive malignancy with a poor prognosis, closely linked to the tumor microenvironment (TME). Emerging evidence highlights the critical role of gastric cancer-associated mesenchymal stem cells (GC-MSCs) in recruiting neutrophils and facilitating neutrophil extracellular traps (NETs) formation, thereby remodeling the tumor microenvironment (TME) and promoting tumor progression, immune modulation, and metastasis.

High-risk human papillomavirus (HPV) is a central factor in cervical cancer development, largely due to its E6 and E7 oncoproteins that disrupt normal cellular regulation. This study explored the influence of high-risk HPV on the expression of PI3K and the long non-coding RNAs (lncRNAs) MALAT1, H19 and LINC00460 in cervical cells. Using a case-control design, cervical liquid samples from 50 HPV-positive patients and 20 healthy controls were analysed via quantitative real-time PCR, with statistical methods employed to assess correlations between viral oncoproteins and target gene expression. Results demonstrated a significant upregulation of PI3K (24.59-fold change, p < 0.036), MALAT1 (9.75-fold change, p < 0.005), LINC00460 (1.15-fold change, p < 0.013) and H19 (7.1-fold change, p < 0.018) in HPV-infected samples, indicating their potential role in HPV-mediated oncogenesis. Although correlation analysis revealed trends between E6/E7 and certain lncRNAs, these were not statistically significant. Overall, these findings deepen our understanding of the molecular changes linked to high-risk HPV infections and identify PI3K, MALAT1 and H19 as promising biomarkers and therapeutic targets for cervical cancer. Future studies should further investigate these interactions to enhance early detection and improve treatment strategies for HPV-associated malignancies.