Biological Procedures Online最新文献

{"title":"Piperlongumine Inhibits Lung Cancer Growth by Inducing Endoplasmic Reticulum Stress Leading to Suppression of M2 Macrophage Polarization.","authors":"Yixin Zhou, Wenjin Teng, Jianchun Wu, Yingbin Luo, Yuli Wang, Yan Li","doi":"10.1186/s12575-025-00279-0","DOIUrl":"10.1186/s12575-025-00279-0","url":null,"abstract":"<p><p>Lung cancer is the leading cause of cancer-related deaths globally. Prolonged targeted therapy use can lead to drug resistance and target mismatches, necessitating more effective and safer treatment strategies. Recent research has focused on the tumor microenvironment, which includes immune and stromal cells that play roles in tumor proliferation, metastasis, and neovascularization. Tumor-associated macrophages (TAMs) are key immune cells in the tumor microenvironment, promoting tumor invasion, metastasis, and immune escape. Their infiltration density in lung cancer tissue is a poor prognostic factor. Piperlongumine (PL), extracted from Piper longum, possesses antitumor and anti-inflammatory properties, inducing apoptosis and inhibiting invasion and metastasis in lung cancer cells. This study aims to elucidate the correlation between endoplasmic reticulum stress (ERS) in lung cancer cells and M2-type TAM polarization and the role of PL in regulating lung cancer progression. The network pharmacologic analysis revealed that Piperlongumine inhibits lung cancer progression by inducing endoplasmic reticulum stress. In vivo experiments demonstrated that Piperlongumine significantly reduced tumor volume and decreased the proportion of M2-type macrophages. Within the co-culture system, lung cancer cells were shown to promote macrophage M2-type polarization and enhance cancer cell migration. Piperlongumine effectively inhibited these effects by inducing endoplasmic reticulum stress in cancer cells, thereby reducing M2 polarization and cell migration. The addition of endoplasmic reticulum stress inhibitor 4-PBA counteracted Piperlongumine's effects, further underscoring the crucial role of ERS in the treatment mechanism. Piperlongumine suppresses lung cancer growth by inducing endoplasmic reticulum stress, which inhibits macrophage M2-type polarization and reduces cell migration. These findings support Piperlongumine's potential as a therapeutic agent and offer a foundation for targeting endoplasmic reticulum stress to modulate TAM function in lung cancer treatment.</p>","PeriodicalId":8960,"journal":{"name":"Biological Procedures Online","volume":"27 1","pages":"18"},"PeriodicalIF":3.7,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12096482/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144126646","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Heterogeneity and efficacy of immunotherapy in multiple cancer: insights from a meta-analysis.","authors":"Weidong Wu, Bin Liu, Qing Zhang, Xiaojuan Zhang, Pengya Feng, Yongliang Jia, Xia Xue","doi":"10.1186/s12575-025-00274-5","DOIUrl":"10.1186/s12575-025-00274-5","url":null,"abstract":"<p><strong>Background: </strong>Immunotherapy has been recognized as a significant advancement in cancer treatment by promoting the body's immune system to identify and eliminate cancer cells more effectively. Unlike conventional therapies, immunotherapy can enhance the natural capabilities of human immune system. Chimeric Antigen Receptor T-cell (CAR-T) therapy involves genetical-modified T-cells from patients to better catch and attack cancer cells. Up to date, CAR-T therapy has shown particular promise in treating certain types of leukemia and lymphoma, highlighting the transformative potential of immunotherapy.</p><p><strong>Results: </strong>Literature data search using PubMed, CNKI, and Wanfang were searched to collect eligible studies up to January 2025. The primary outcomes of complete response rate (CRR), objective response rate (ORR), dead rate (DR), and other adverse reactions were evaluated. Secondary outcomes (CRR, ORR, and DR) of subgroup analysis from different cancer types, origins, and outcomes for survival rate were analyzed for our final results. A total of 649 studies were initially identified through database searching. After removing duplicates and non-clinical cancer studies, 32 eligible studies were included in this work. The pooled data included 819 patients for objective response rate (ORR), 843 patients for complete response rate (CRR), and 868 patients for dead event. In the included studies, 24 reported ORR data, revealing an objective response rate of 84.86% (695/819) with little heterogeneity (OR: 0.87, 95% CI 0.80-0.91, P = < 0.01, I² = 61%); 24 studies showed a CRR of 65.30% (491/843) with significant heterogeneity (OR: 0.58, 95% CI: 0.43-0.72, P < 0.01, I² = 84%); 27 studies showed a mortality rate of 23.73% (206/868) with significant heterogeneity (OR: 0.19, 95% CI: 0.11-0.32, P < 0.01, I² = 77%). Subgroup analysis based on cancer type revealed that ORR was higher in multiple myeloma (86.77%, 400/461) compared with leukemia (84.92%, 259/305) and lymphoma (67.92%, 36/53). In parallel, heterogeneity observed based on case origins suggested that Chinese cases showed significantly higher ORR, CRR, and survival rates compared with American ones.</p><p><strong>Conclusions: </strong>This meta-analysis provides valuable insights into the potential of immunotherapy, particularly CAR-T, in cancer treatment. Findings showed the different efficacy and safety of immunotherapy in treating multiple cancers, with various objective response rates. Continued studies from more trials with different populations are needed to optimize their efficacy in further cancer treatment and precision medicine.</p>","PeriodicalId":8960,"journal":{"name":"Biological Procedures Online","volume":"27 1","pages":"17"},"PeriodicalIF":3.7,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12090696/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144101055","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PRRG4 Brain-Specific Conditional Knockout Mice Display Autism Spectrum Disorder-Like Behaviors.","authors":"Luxi Shen, Lan Chen, Yuping Tang, Yeyao Yan, Ting Xiong, Yong Liu, Hongzhi Li, Haihua Gu","doi":"10.1186/s12575-025-00280-7","DOIUrl":"10.1186/s12575-025-00280-7","url":null,"abstract":"<p><strong>Background: </strong>Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized primarily by social deficits and repetitive behaviors. The mechanisms of ASD are complex and are not yet fully understood, although many ASD risk genes and mouse models have been reported. It has been suggested that deletion of PRRG4 (proline-rich and Gla domain 4) deletion may contribute to autism symptoms in patients with WAGR (Wilms' tumor, aniridia, gonadoblastoma, mental retardation) syndrome. The mouse model with PRRG4 gene deletion has not been reported so far. This study investigated whether brain-specific conditional knockout of PRRG4 induces ASD-like symptoms in mice by crossing the PRRG4^fl/fl mice with Emx1-Cre mice, which express Cre in the cerebral cortex and hippocampus.</p><p><strong>Results: </strong>The PRRG4 brain-specific knockout (PRRG4^fl/^fl-Cre⁺, PRRG4-CKO) mice exhibited social deficits, repetitive behaviors, and anxiety-like symptoms compared to PRRG4^fl/fl control mice according to the results of various behavioral tests. PRRG4 knockout led to the increase in total dendritic length, branching, and dendritic spine density in the pyramidal neurons of the cerebral cortex and hippocampus, as well as enhanced levels of synaptic proteins including SYP and PSD95. Immunoprecipitation experiment with PRRG4 antibodies showed dramatic decreased interaction of PRRG4 and MAGI2 proteins in brain tissues from PRRG4-CKO mice compared to PRRG4^fl/fl control mice. GST-RBD pull-down assay showed a significant decrease in RhoA-GTP levels in the cerebral cortex and hippocampus of PRRG4-CKO mice.</p><p><strong>Conclusions: </strong>Brain-specific conditional knockout of the PRRG4 in mice leads to ASD-like symptoms. PRRG4 protein may regulate dendritic and synaptic development in mice by activating RhoA through interaction with MAGI2. These findings provide evidence for a comprehensive understanding of PRRG4 function in vivo and support the association between PRRG4 loss and ASD phenotypes observed in WAGR syndrome.</p>","PeriodicalId":8960,"journal":{"name":"Biological Procedures Online","volume":"27 1","pages":"16"},"PeriodicalIF":3.7,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12082955/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144085749","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Negative Regulation of Cell Adhesion as a Driver of Brain Metastasis in NSCLC Patients with EGFR Amplification.","authors":"Hainan Yang, Congli Hu, Yu Zhou, Taoyuan Tong, Luyao Qi, Weifang Yuan, Changguo Shan, Weiping Hong, Lei Wen, Caicun Zhou, Ming Lei","doi":"10.1186/s12575-025-00277-2","DOIUrl":"https://doi.org/10.1186/s12575-025-00277-2","url":null,"abstract":"<p><p>Brain metastases are strongly associated with a poor prognosis. Experimental animal models have provided valuable insights into the complex biology underlying brain metastasis, and translating these findings could pave the way for innovative management strategies for patients with brain metastases. Between May 2019 and June 2023, twenty-four lung cancer patients and thirty patients with brain metastases from lung cancer were enrolled at Guangdong Sanjiu Brain Hospital. Next-generation targeted panel sequencing (NGS) was performed on lung cancer tissue and surgical specimens from brain tumors for each patient. Brain metastasis mouse models were established through intracardiac injections, and the brain metastasis rate was analyzed. Our results showed that the rate of EGFR amplification was significantly higher in patients with brain metastases compared to lung cancer patients (40% vs. 12%). EGFR-overexpressing PC9 cell lines demonstrated significantly enhanced proliferation and infiltration abilities compared to their parental PC9 counterparts, as evidenced by CCK-8, wound healing, and transwell assays. Moreover, we observed a much higher brain metastasis rate in mice injected with EGFR-overexpressing PC9 cells compared to those injected with parental PC9 cells. RNA sequencing and Gene Ontology (GO) analysis revealed that differentially expressed genes were primarily associated with the \"negative regulation of cell adhesion\" in biological processes (BP) and \"collagen-containing extracellular matrix\" in cellular components (CC). This study identifies the negative regulation of cell adhesion as a key driver of brain metastasis in NSCLC patients with EGFR amplification.</p>","PeriodicalId":8960,"journal":{"name":"Biological Procedures Online","volume":"27 1","pages":"15"},"PeriodicalIF":3.7,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12016210/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143967386","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differences in Fatty Acid Metabolism between MCDD and HFD Induced Metabolic Dysfunction-associated Fatty Liver Disease Model Mice.","authors":"Jia-Xuan Wang, Xin-Zhu Liu, Zhen Guo, Hui-Lin Zhang, Li Qi, Jia Liu, Ping Liu, Guo-Xiang Xie, Xiao-Ning Wang","doi":"10.1186/s12575-025-00276-3","DOIUrl":"https://doi.org/10.1186/s12575-025-00276-3","url":null,"abstract":"<p><strong>Background: </strong>The global incidence of metabolic dysfunction-associated fatty liver disease (MAFLD) is increasing annually, which has become a major public-health concern. MAFLD is typically associated with obesity, hyperlipemia, or metabolic syndrome. Dietary induction is one of the most common methods for preparing animal models of MAFLD. However, there are phenotypic differences between methionine-choline-deficient diet (MCDD) and high fat diet (HFD) models.</p><p><strong>Methods: </strong>To explore the differences in hepatic fatty acid metabolism between MCDD and HFD induced MAFLD, we analyzed serum and liver tissue from the two MAFLD models.</p><p><strong>Results: </strong>We found that liver fat accumulation and liver function damage were common pathological features in both MAFLD models. Furthermore, in the MCDD model, the expression of hepatic fatty acid transport proteins increased, while the expression of hepatic fatty acid efflux proteins and mRNA decreased, along with a decrease in blood lipid levels. In the HFD model, the expression of hepatic fatty acid uptake proteins, efflux proteins and efflux mRNA increased, along with an increase in blood lipid levels.</p><p><strong>Conclusion: </strong>Impaired fatty acid oxidation and increased hepatic fatty acid uptake play key roles in the pathogenesis of the two MAFLD models. The inverse changes in de novo lipogenesis and fatty acid efflux may represent an important pathological mechanism that leads to the phenotypic differences between the MCDD and HFD models.</p>","PeriodicalId":8960,"journal":{"name":"Biological Procedures Online","volume":"27 1","pages":"14"},"PeriodicalIF":3.7,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11998272/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143960948","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Construction of a circRNA-miRNA-mRNA Regulatory Network for the Immune Regulation of Lung Adenocarcinoma.","authors":"Hanyi Li, Xin Jin, Wei Li, Fan Ren, Tong Li, Xuanguang Li, Haochuan Yu, Dianxun Fu, Zuoqing Song, Song Xu","doi":"10.1186/s12575-025-00275-4","DOIUrl":"https://doi.org/10.1186/s12575-025-00275-4","url":null,"abstract":"<p><strong>Background: </strong>Recent research has highlighted the significance of circular RNAs (circRNAs) as pivotal regulators in the progression of tumors and the therapeutic response in non-small cell lung cancer (NSCLC). These circRNAs function through a sponge mechanism, interacting with microRNAs (miRNAs) to modulate mRNA expression levels. Nevertheless, the precise role of the circRNA-miRNA-mRNA regulatory network in immune regulation within lung adenocarcinoma (LUAD) remains inadequately understood.</p><p><strong>Methods and materials: </strong>We utilized microarray datasets from the GEO NCBI database (GSE101586) to identify differentially expressed circRNAs (DEcircRNAs) in LUAD. CircBank was employed to predict the target miRNAs of DEcircRNAs, which were subsequently intersected with miRNAs from the GSE36681 database. The identified miRNAs were then predicted to target mRNAs using miRDB and miWalk, and intersections with immune-related genes from the IMMPORT database were analyzed. Protein-protein interaction (PPI) networks were constructed using Cytoscape software. The DAVID functional annotation tool was utilized to explore potential biological processes, molecular functions, and KEGG pathways associated with LUAD. Gene expression and Kaplan-Meier survival analyses were conducted to establish a key regulatory network and to assess immune cell infiltration and Pearson correlation for significant target genes. Finally, we selected the most significantly upregulated circRNA with differential expression for validation through in vitro experiments.</p><p><strong>Results: </strong>Our analysis identified a total of 7 upregulated and 42 downregulated circRNAs, along with 10 significant miRNAs and 20 target mRNAs. KEGG enrichment analysis indicated that these components are primarily enriched in the ErbB signaling pathway. Furthermore, Gene Ontology (GO) analysis revealed significant enrichment in responses to organic substances, cytokine-mediated signaling pathways, cellular responses to cytokines, responses to chemical stimuli, steroid hormone receptor activity, ErbB-3 class receptor binding, oxysterol binding, signal receptor activity, and molecular transducer activity. Notable core mRNAs identified included OAS1, VIPR1, and PIK3R1. Subsequently, we constructed a regulatory network comprising 6 DEcircRNAs, 3 DEmiRNAs, and 3 DEmRNAs. Through ssGSEA and CIBERSORT analyses, we observed significant differences in immune cell infiltration levels between the NSCLC cohort and the control group. Knocking down the expression of hsa_circ_0079557 significantly inhibited the viability, proliferation, migration, and invasion of LUAD cells.</p><p><strong>Conclusion: </strong>We have established a circRNA-miRNA-mRNA regulatory network that offers novel insights into the molecular mechanisms governing immune regulation in LUAD. Future research should aim to translate these findings into clinical applications to enhance patient outcomes.</p>","PeriodicalId":8960,"journal":{"name":"Biological Procedures Online","volume":"27 1","pages":"13"},"PeriodicalIF":3.7,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11983969/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143976172","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessment of MALDI-TOF MS for Arthropod Identification Based on Exuviae Spectra Analysis.","authors":"Rym Bouledroua, Adama Zan Diarra, Remy Amalvict, Jean-Michel Berenger, Ahmed Benakhla, Philippe Parola, Lionel Almeras","doi":"10.1186/s12575-024-00260-3","DOIUrl":"10.1186/s12575-024-00260-3","url":null,"abstract":"<p><p>MALDI-TOF MS is an innovative tool for identifying hematophagous and non-hematophagous arthropods at various life stages. However, identification by MALDI-TOF MS currently requires euthanizing of the specimen, hindering further phenotypic tests. All arthropods have a common factor, molting of their exoskeletons leaving a remaining structure known as the exuviae. This phenomenon is indispensable for their growth and can evidence past arthropod presence. This study assessed the performance of MALDI-TOF MS biotyping for arthropod identification using exuviae from nine distinct laboratory-reared species (Aedes aegypti, Anopheles coluzzii, Cimex lectularius, C. hemipterus, Pediculus humanus humanus, Triatoma infestans, Rhodnius prolixus, Supella longipalpa and Blattella germanica) compared its efficiency with a molecular identification approach using DNA sequencing. Molecular analysis showed low DNA quantity in exuviae (n = 108) across species, resulting in low success of COI, 16s, and 18s amplification (50.0%), depending on the species and sequencing (10.2%). The establishment of an exuviae protocol for MS submission yielded spectra of high reproducibility and specificity per species. After upgrading a homemade reference MS database with exuviae spectra, a query with remaining spectra revealed that 100% of samples were correctly identified, with 85.8% (278/324) exceeding the threshold score value for reliable identification. MALDI-TOF MS showed high efficiency in identifying various arthropod species based on their exuviae. This approach is a groundbreaking development in the field of entomology underlining that MALDI-TOF outperformed traditional methods of exuviae identification, including morphological and molecular tools. It also prevents specimen sacrifice which could be used for complementary analyses.</p>","PeriodicalId":8960,"journal":{"name":"Biological Procedures Online","volume":"27 1","pages":"12"},"PeriodicalIF":3.7,"publicationDate":"2025-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11971817/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143787696","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bio-SS-TS as a Targeted Antitumor Drug Exerts an Anti-Liver Cancer Effect by Enhancing Mitochondria-Dependent Apoptosis.","authors":"Jian Li, Yuanhua Qin, Mengjuan Li, Jingli Shang, Hang Chen, Yadi Liu, Bingjie Liu, Pingxin Zhou, Tiesuo Zhao, Ge Wang, Chunpo Ge, Yu Zhang, Huijie Jia, Feng Ren","doi":"10.1186/s12575-025-00272-7","DOIUrl":"https://doi.org/10.1186/s12575-025-00272-7","url":null,"abstract":"<p><p>Developing targeted therapeutic drugs for liver cancer remains a significant scientific and clinical challenge. Previous research by the authors showed that taraxasterol (TS) can enhance the antitumor immune response of T-lymphocytes, inhibiting the growth of liver cancer cells both in vivo and in vitro. To improve the targeting ability and efficacy of TS, the authors synthesized a novel compound, Bio-SS-TS, which utilizes the high expression of biotin receptors on tumor cell membranes to link biotin to TS for increased targeting to hepatocellular carcinoma cells, and its disulfide bond can be specifically hydrolyzed by high - level glutathione (GSH) in tumor cells to release the active component TS. In vitro, Bio-SS-TS reduced liver cancer cell (HepG2 and Huh7) proliferation, impaired mitochondrial membrane potential, decreased intracellular GSH content in tumor cells, increased the reactive oxygen species level, and promoted the release of cytochrome c. Endogenous GSH in cancer cells reduced the disulfide bond in Bio-SS-TS, releasing active TS components. In vivo, treatment with Bio-SS-TS caused no significant change in mouse body weight and no toxicity to the main organs. The present study comprehensively demonstrates that Bio-SS-TS exerts a potent anti - liver cancer effect by enhancing mitochondria-dependent apoptosis, which may provide a new candidate for targeted liver cancer therapy.</p>","PeriodicalId":8960,"journal":{"name":"Biological Procedures Online","volume":"27 1","pages":"11"},"PeriodicalIF":3.7,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11951608/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143741895","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Therapeutic Targets for Gastric Cancer: Mendelian Randomization and Colocalization Analysis.","authors":"Yong Wang, Zongkai Liu, Wenjia Liu, Ying Sun, Zhaidong Liu","doi":"10.1186/s12575-025-00273-6","DOIUrl":"10.1186/s12575-025-00273-6","url":null,"abstract":"<p><strong>Background: </strong>Gastric cancer (GC) is one of the most prevalent malignancies in the world. Most patients are diagnosed at advanced stages of the disease, primarily attributable to the insidious nature of early symptoms and the infrequent occurrence of routine screening. Further biomarkers are still needed for more comprehensive analysis, targeted prognostication, and effective treatment strategies. Plasma proteins are promising biomarkers and potential drug targets in GC. This study aims to identify potential therapeutic targets for GC by conducting a comprehensive proteome-wide Mendelian randomization (MR) and colocalization analyses.</p><p><strong>Methods: </strong>Plasma proteins were obtained from the UK Biobank Pharma Proteomics Project (UKB-PPP), including Genome-Wide Association Study(GWAS)data of 1463 plasma proteins. Genetic associations with cancer were derived from the European Bioinformatics Institute (EBI) database, including 1029 patients and 475,087 controls (dataset: ebi-a-gcst90018849). MR analysis was conducted to assess the association between plasma proteins and the risk of developing cancer. Additionally, colocalization analysis was employed to investigate whether the identified proteins and gastric cancer exhibited shared incidental variants. Finally, using the extensive Finnish database in the R9 version, the potential harmful effects of target proteins on the treatment of gastric cancer were explored through the whole phenomenon association study (PheWAS).</p><p><strong>Result: </strong>The results showed that 15 proteins may be associated with the risk of gastric cancer, and one protein is expected to become a therapeutic target for gastric cancer. There was a positive genetic association between plasma levels of 11 proteins and increased GC risk, while 4 proteins exhibited an inverse association with GC risk (P < 0.05). Colocalization analysis revealed that PPCDC and GC exhibited shared genetic loci among the 15 proteins examined, indicating that PPCDC may serve as potential direct target for intervention in GC. Further phenotype wide association studies showed that PPCDC (P < 0.05) could be associated with certain potential side effects.</p><p><strong>Conclusion: </strong>Our research examined the causal relationship between plasma proteins and gastric cancer, shedding light on potential therapeutic targets. These findings have significant implications for the development of early diagnostic markers and targeted therapies for GC, potentially improving patient outcomes and survival rates. Future studies should validate these findings in diverse populations and explore the clinical applications of these targets.</p>","PeriodicalId":8960,"journal":{"name":"Biological Procedures Online","volume":"27 1","pages":"10"},"PeriodicalIF":3.7,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11916961/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143656015","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tumor Prognostic Risk Model Related to Monocytes/Macrophages in Hepatocellular Carcinoma Based on Machine Learning and Multi-Omics.","authors":"Xinliang Wan, Yongchun Zou, Qichun Zhou, Qing Tang, Gangxing Zhu, Luyu Jia, Xiaoyan Yu, Handan Mo, Xiaobing Yang, Sumei Wang","doi":"10.1186/s12575-025-00270-9","DOIUrl":"10.1186/s12575-025-00270-9","url":null,"abstract":"<p><p>Tumor-associated macrophages (TAMs) are crucial in hepatocellular carcinoma (HCC) development and invasion. This study explores monocyte/ macrophage-associated gene expression profiles in HCC, constructs a prognostic model based on these genes, and examines its relationship with drug resistance and immune therapy responses. Single-cell RNA sequencing(scRNA-seq) data from 10 HCC tissue biopsy samples, totaling 24,597 cells, were obtained from the GEO database to identify monocyte/macrophage-associated genes. A prognostic model was constructed and validated using external datasets and Western blot. Relationships between the model, clinical correlates, drug sensitivity, and immune therapy responses were investigated. From scRNA-seq data, 2,799 monocyte/macrophage marker genes were identified. Using the TCGA dataset, a prognostic model based on the single-gene UQCRH was constructed, stratifying patients into high-risk and low-risk groups based on overall survival rates. High-risk group patients showed reduced survival rates and higher UQCRH expression in tumor tissues. Western blot analysis further confirmed the elevated expression of UQCRH in HCC cell lines. Spatial transcriptomics analysis revealed that high UQCRH expression co-localized with malignant cells in the tumor tissue. Drug sensitivity analysis revealed that the high-risk group had lower sensitivity to sorafenib and axitinib. Immune therapy response analysis indicated poorer outcomes in the high-risk group, with more pronounced APC inhibition and a weaker IFN-II response. Clinical indicator analysis showed a positive correlation between high UQCRH expression and tumor invasion. Enrichment analysis of UQCRH and associated molecules indicated involvement in oxidative phosphorylation and mitochondrial electron transport. This study introduces a prognostic model for HCC patients based on monocyte/macrophage marker genes. The single-gene model predicts HCC patient survival and treatment outcomes, identifying high-risk individuals with varying drug sensitivities and immune suppression states.</p>","PeriodicalId":8960,"journal":{"name":"Biological Procedures Online","volume":"27 1","pages":"9"},"PeriodicalIF":3.7,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11892220/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143596135","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}