Aldehyde dehydrogenase 3A1 (ALDH3A1) is an NAD⁺-dependent enzyme that is closely related to tumor development. However, its role in non-small-cell lung cancer (NSCLC) has not been elucidated. This study aimed to clarify the mechanism of ALDH3A1 and identify potential therapeutic targets for NSCLC. Here, for the first time, we found that ALDH3A1 expression could be induced by a hypoxic environment in NSCLC. ALDH3A1 was highly expressed in NSCLC tissue, especially in some late-stage patients, and was associated with a poor prognosis. In mechanistic terms, ALDH3A1 enhances glycolysis and suppresses oxidative phosphorylation (OXPHOS) to promote cell proliferation by activating the HIF-1α/LDHA pathway in NSCLC. In addition, the results showed that ALDH3A1 was a target of β-elemene. ALDH3A1 can be downregulated by β-elemene to inhibit glycolysis and enhance OXPHOS, thus suppressing NSCLC proliferation in vitro and in vivo. In conclusion, hypoxia-induced ALDH3A1 is related to the energy metabolic status of tumors and the efficacy of β-elemene, providing a new theoretical basis for better clinical applications in NSCLC.

Background: Gastric cancer (GC) is the fifth most commonly diagnosed cancer worldwide, and its poor prognosis is predominantly attributed to distant metastasis. The liver is the primary site of GC metastasis. However, there is no universally approved treatment regimen for liver metastasis in GC. The aim of this article is to review the current research status and trends of liver metastasis of GC worldwide. Methods: The authors utilized the Web of Science Core Collection database to identify articles on liver metastasis from GC published between 2000 and 2022. The authors used bibliometric methods to analyze authors, institutions, countries, journals, and references through CiteSpace and VOSviewer. A total of 1003 articles were included in this study. Results: Japan published the most articles in the field, followed by China. Nagoya University is the leading institution in the field of liver metastases in GC. Yasuhiro Kodera from Japan has made significant achievements in this area. The authors identified GC to be the most influential journal in this field. Using cluster analysis, the keywords were divided into four major clusters:(1) the molecular mechanism of GC liver metastasis, (2) prognosis, (3) liver resection, and (4) chemotherapy. Conclusion: Our study systematically summarizes the results of GC liver metastasis research from 2000 to 2022 and describes and predicts research hotspots and trends on a global scale. Research on the molecular mechanisms of GC liver metastasis will become a hot topic in the future, and the expansion of the surgical treatment scope and the advancement of translational therapy will benefit more patients.

Background:NOS3 (endothelial NOS, eNOS) is a member of the nitric oxide synthase (NOS) enzyme family, mainly participating in nitric oxide (NO) generation. NOS3 has been reported to inhibit apoptosis and promote angiogenesis, proliferation, and invasiveness. However, the expression pattern of NOS3 and its diagnostic and prognostic potential has not been investigated in a pan-cancer perspective.Methods: Data from the Genotype-Tissue Expression (GTEx), the Cancer Genome Atlas (TCGA), the Cancer Cell Line Encyclopedia (CCLE), and the Cancer Therapeutics Response Portal (CTRP) were employed and NOS3 expression was comprehensively analyzed in normal tissues, cancer tissues, and cell lines. Immunohistochemical staining of tissue sections were used to validate the prognostic role of NOS3 in gastric cancer patients. GSVA and GSEA analyses were performed to investigate signaling pathways related to NOS3 expression.Results: In normal tissues, NOS3 was expressed highest in the spleen and lowest in the blood. NOS3 expression was increased in stomach adenocarcinoma (STAD) and significantly associated with poor prognosis of patients. Immunohistochemical staining validated that NOS3 was an independent prognostic factor of gastric cancer. Several canonical cancer-related pathways were found to be correlated with NOS3 expression in STAD. The expression of NOS3 was related to the response to QS-11 and brivinib in STAD.Conclusions:NOS3 was an independent prognostic factor for patients with STAD. Increased expression of NOS3 influenced occurrence and development of STAD through several canonical cancer-related pathways. Drug response analysis reported drugs to suppress NOS3. NOS3 might be a novel target for gastric cancer treatment.

Background: Spatial metabolomics has revolutionized cancer research by offering unprecedented insights into the metabolic heterogeneity of the tumor microenvironment (TME). Unlike conventional metabolomics, which lacks spatial resolution, spatial metabolomics enables the visualization of metabolic interactions among cancer cells, stromal components, and immune cells within their native tissue context. Despite its growing significance, a systematic and visualized analysis of spatial metabolomics in cancer research remains lacking, particularly in the integration of multi-omics data and the standardization of methodologies for comprehensive tumor metabolic mapping.Objectives: This study aims to conduct a bibliometric analysis to systematically evaluate the development trends, key contributors, research hotspots, and future directions of spatial metabolomics in cancer research.Methods: A bibliometric approach was employed using data retrieved from the Web of Science Core Collection. Analytical tools such as VOSviewer and CiteSpace were utilized to visualize and assess co-citation networks, keyword co-occurrence, and institutional collaborations. Key metrics, including publication trends, authorship influence, country contributions, and journal impact, were analyzed to map the research landscape in this domain.Results: A total of 182 publications on spatial metabolomics in cancer research were identified over the past two decades, with a notable surge in research output beginning in 2018. The field has experienced accelerated growth, with an annual average of 40 publications since 2021, reflecting its increasing relevance in cancer studies. Among 28 contributing countries, China (n=53), the United States (n=35), Germany (n=18), and the United Kingdom (n=13) have been the most active contributors. China leads in publication volume, while the United States exhibits the highest citation impact, indicating significant research influence. International collaboration networks are particularly strong among the United States, Germany, and China, underscoring the global interest in this emerging field. Analysis of key authors and institutions identifies He Jiuming as the most prolific author and Song Xiaowei as the researcher with the highest average citations. Other influential authors include Abliz Zeper and Sun Chenglong. Leading research institutions driving advancements in this field include the Chinese Academy of Medical Sciences, Peking Union Medical College, Harvard Medical School, and Stanford University. Regarding journal impact, Nature Communications (n=11), Journal of Pharmaceutical Analysis (n=9), and Nature Methods (n=8) are the most active publishing platforms in this domain. Citation analysis reveals that Cell, BioEssays, and Genome Medicine are among the most highly cited journals, reflecting the interdisciplinary nature of spatial metabolomics research.

Epithelial ovarian cancer (EOC) has a poor prognosis and high mortality rate; patients are easy to relapse with standard therapies. So, there is an urgent need to develop novel drugs. In this study, differentially expressed genes (DEGs) of EOC were identified in The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Enrichment and protein–protein interaction (PPI) analyses were performed. The drug candidate which has the possibility to treat EOC was predicted by Connectivity Map (CMAP) databases. Moreover, molecular docking was selected to calculate the binding affinity between drug candidate and hub genes. The cytotoxicity of drug candidates was assessed by MTT and colony formation analysis, the proteins coded by hub genes were detected by Western blots, and apoptosis analysis was evaluated by flow cytometry. Finally, 296 overlapping DEGs (|log 2 fold change|>1; q-value <0.05), which were principally involved in the cell cycle (p < 0.05), and cyclin-dependent kinase 1 (CDK1) were screened as the significant hub gene from the PPI network. Furthermore, the 21 drugs were extracted from CMAPs; among them, piperlongumine (PL) showed a lower CMAP score (-0.80, -62.92) and was regarded as the drug candidate. Furthermore, molecular docking results between PL and CDK1 with a docking score of –8.121 kcal/mol were close to the known CDK1 inhibitor (–8.24 kcal/mol). Additionally, in vitro experiments showed that PL inhibited proliferation and induced apoptosis via targeting CDK1 in EOC SKOV3 cells. Our results reveal that PL may be a novel drug candidate for EOC by inhibiting cell cycle.