Molecular Biotechnology最新文献

{"title":"Differential Gene Analysis of Langerhans Cell Histiocytosis and the Significance of MMP1-Targeted Drug Repositioning.","authors":"Xiao Feng, Xin Yuan, Yang-Yang Hua, Jing Tao, Nan Zhang","doi":"10.1007/s12033-024-01186-7","DOIUrl":"10.1007/s12033-024-01186-7","url":null,"abstract":"<p><p>Langerhans cell histiocytosis (LCH) is a rare condition predominantly affecting young children. Activation of the MAPK pathway has offered key new insights into the pathogenesis of LCH; however, the precise mechanisms underlying its occurrence and development are still far from being completely elucidated. There is still a relapse/reactivation rate in patients with multisystem LCH. Therefore, this study aimed to investigate other potential LCH pathophysiologies and prospective therapeutic targets. The gene expression omnibus (GEO) database was used to retrieve gene expression profiles of LCH (GSE16395). Three distinct types of analyses were performed after identifying the common differentially expressed genes (DEGs) in LCH: hub gene identification, functional annotation, module construction, drug repositioning, and expression analysis via immunohistochemistry (IHC). We identified 417 common DEGs and 50 central hub genes. This functional study highlighted the significance of keratinization, skin development, and inflammation. In addition, we predicted new drug candidates (RS2 drugs targeting matrix metalloprotease1, MMP1) that could be used for LCH treatment. Finally, gene-miRNA and gene-TF networks and immune cell infiltration were analyzed for MMP1-related genes. MMP1 expression levels in LCH tissues were validated by IHC. Our study identified the central communal genes and novel drug candidates. These shared pathways and hub genes offer new perspectives on future mechanisms of action and therapeutic targets.</p>","PeriodicalId":18865,"journal":{"name":"Molecular Biotechnology","volume":" ","pages":"2098-2110"},"PeriodicalIF":2.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140922474","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Curcumin Inhibits Lipopolysaccharide-Induced Inflammation Through the HMGB1/NF-κB Signaling Pathway to Promote the Osteogenic Differentiation of Bone Marrow Mesenchymal Stem Cells.","authors":"Jimei Zhang, Donggang Mou, Ling Zhu, Jianping Zhou, Qunying Yu, Guangyuan Yang, Chaoli Luo, Jianguo Meng, Kewang Mao, Jing Liu, Bo Yan, Xuming Yang","doi":"10.1007/s12033-025-01437-1","DOIUrl":"https://doi.org/10.1007/s12033-025-01437-1","url":null,"abstract":"<p><p>Curcumin has strong anti-inflammatory properties and promotes the osteogenic differentiation of human bone marrow mesenchymal stem cells (hBMSCs). The aim of this study was to explore the role and potential molecular mechanism of curcumin in ameliorating osteogenic differentiation disorders caused by inflammation. We used LPS to induce an inflammatory response in hBMSCs. The expression of related mRNAs and proteins was detected by RT‒qPCR, Western blotting, immunofluorescence, and ELISA. The osteogenic differentiation of hBMSCs was detected by alkaline phosphatase (ALP) staining and alizarin red S (ARS) staining. The results showed that after LPS treatment, the levels of the inflammatory cytokines TNF-α, IL-6 and IL-1β in hBMSCs increased, and the activity of ALP, the level of calcium salt deposition and the expression levels of the osteogenic proteins Runx2, COL1, OCN and OPN significantly decreased. The curcumin treatment alleviated this effect. These results indicated that curcumin improved the LPS-induced inflammation and osteogenic differentiation disorder in hBMSCs. Further studies revealed that the therapeutic effect of curcumin was caused by the inhibition of HMGB1 expression. From a mechanistic perspective, curcumin inhibits LPS-induced inflammation by inhibiting the expression of HMGB1, thereby inhibiting the NF-κB pathway and activating the NRF2 pathway, thereby improving the disordered osteogenic differentiation of hBMSCs. In conclusion, curcumin can reduce the LPS-induced inflammation of hBMSCs and ameliorate their osteogenic differentiation disorders.</p>","PeriodicalId":18865,"journal":{"name":"Molecular Biotechnology","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143972397","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sophoraflavanone G Inhibits RANKL-Induced Osteoclastogenesis via MAPK/NF-κB Signaling Pathway.","authors":"Xinchun Li, Wei Deng, Kai Tang, Shiyin Zhang, Zixuan Liang, Weiwen Liu, Yongyu Li, Zhida Zhang, Wenhua Zhao, Jian Zou","doi":"10.1007/s12033-024-01185-8","DOIUrl":"10.1007/s12033-024-01185-8","url":null,"abstract":"<p><p>Osteoporosis is a common chronic bone metabolism disorder characterized by decreased bone mass and reduced bone density in the bone tissue. Osteoporosis can lead to increased fragility of the skeleton, making it prone to brittle fractures. Osteoclasts are macrophage-like cells derived from hematopoietic stem cells, and their excessive activity in bone resorption leads to lower bone formation than absorption during bone remodeling, which is one of the important factors inducing osteoporosis. Therefore, how to inhibit osteoclast formation and reducing bone loss is an important direction for treating osteoporosis. Sophoraflavanone G, derived from Sophora flavescens Alt and Rhizoma Drynariae, is a flavonoid compound with various biological activities. However, there have been few studies on osteoporosis and osteoclasts so far. Therefore, we hypothesize that genistein G can inhibit osteoclast differentiation, alleviate bone loss phenomenon, and conduct in vitro and in vivo experiments for research and verification purposes.</p>","PeriodicalId":18865,"journal":{"name":"Molecular Biotechnology","volume":" ","pages":"2085-2097"},"PeriodicalIF":2.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141080517","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the Targets and Molecular Mechanisms of Curcumin for the Treatment of Bladder Cancer Based on Network Pharmacology, Molecular Docking and Molecular Dynamics.","authors":"Jun Li, Shujie Feng, Xiong Wang, Bingmei Zhang, Qingmin He","doi":"10.1007/s12033-024-01190-x","DOIUrl":"10.1007/s12033-024-01190-x","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Curcumin, a phenolic compound derived from turmeric, has demonstrated anti-tumor properties in preclinical models of various cancers. However, the exact mechanism of curcumin in treating bladder cancer remains unclear. This study aimed to elucidate the therapeutic targets and molecular mechanisms of curcumin in the treatment of BC through an integrated approach of network pharmacology, molecular docking, and molecular dynamics simulations. PharmMapper, SuperPred, TargetNet, and SwissTargetPrediction were utilized to acquire targets associated with curcumin, while GeneCards, CTD, DisGeNET, OMIM, and PharmGKB databases were utilized to obtain targets related to bladder cancer. The drug-disease interaction targets were obtained using Venny 2.1.0, and GO and KEGG enrichment analyses were then conducted with the DAVID tool. We constructed a protein-protein interaction (PPI) network and identified tenkey targets. In conclusion, AutoDock Tools 1.5.7 was utilized to conduct molecular docking simulations, followed by additional analysis of the central targets through the GEPIA, HPA, cBioPortal, and TIMER databases. A total of 305 potential anticancer targets of curcumin were obtained. The analysis of GO functional enrichment resulted in a total of 1105 terms, including 786 terms related to biological processes (BP), 105 terms related to cellular components (CC), and 214 terms related to molecular functions (MF). In addition, KEGG pathway enrichment analysis identified 170 relevant signaling pathways. Treating bladder cancer could potentially involve inhibiting pathways like the PI3K-Akt signaling pathway, MAPK signaling pathway, EGFR tyrosine kinase inhibitor resistance, and IL-17 signaling pathway. Activating TNF, ALB, CASP3, and ESR1 while inhibiting AKT1, EGFR, STAT3, BCL2, SRC, and HSP90AA1 can also hinder the proliferation of bladder tumor cells. According to the results of molecular docking, curcumin binds to these central targets in a spontaneous manner, exhibiting binding energies lower than - 1.631 kJ/mol. These findings were further validated at the transcriptional, translational and immune infiltration levels. By utilizing network pharmacology and molecular docking techniques, it was discovered that curcumin possesses diverse effects on multiple targets and pathways for treating bladder cancer. It has the potential to impede the growth of bladder tumor cells by suppressing various pathways including the PI3K-Akt and MAPK signaling pathways, as well as pathways associated with EGFR tyrosine kinase inhibitor resistance and the IL-17 signaling pathway. Curcumin could potentially disrupt the cell cycle advancement in bladder cancer cells by increasing the expression of TNF, ALB, CASP3, and ESR1 while decreasing AKT1, EGFR, STAT3, BCL2, SRC, HSP90AA1, and other targeted genes. These findings reveal the possible molecular pathways through which curcumin exerts its anticancer effects in bladder cancer, and this novel research strategy not only p","PeriodicalId":18865,"journal":{"name":"Molecular Biotechnology","volume":" ","pages":"2138-2159"},"PeriodicalIF":2.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141186786","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Resveratrol Inhibits Colorectal Cancer Cell Tumor Property by Activating the miR-769-5p/MSI1 Pathway.","authors":"Hongchang Liu, Liangliang Zhang, Liangliang Hao, Dingwen Fan","doi":"10.1007/s12033-024-01167-w","DOIUrl":"10.1007/s12033-024-01167-w","url":null,"abstract":"<p><p>Resveratrol exhibits inhibitory effects on the progression of various cancers including colorectal cancer (CRC), however, the underlying mechanism in regulating CRC development remains elusive. The present study aims to uncover the role and molecular mechanism of resveratrol in modulating CRC cell tumor properties. NCM460 cells, LoVo cells, SW480 cells, and BALB/c nude mice were utilized in this study. RNA levels of miR-769-5p and musashi RNA-binding protein 1 (MSI1) were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Protein expression was assessed by western blotting or immunohistochemistry assay. Cell viability was analyzed by CCK-8 assay, while cell proliferation and apoptosis were evaluated by 5-Ethynyl-2'-deoxyuridine assay and flow cytometry analysis. Cell migration was investigated by transwell and wound-healing assays. The association between miR-769-5p and MSI1 was identified by a dual-luciferase reporter assay. Tumor formation was analyzed using a xenograft mouse model assay. Compared to control groups, miR-769-5p expression was downregulated, while MSI1 expression was upregulated in CRC tissues and cells. Resveratrol treatment led to increased miR-769-5p expression and decreased MSI1 expression in CRC cells. Resveratrol treatment or miR-769-5p upregulation inhibited CRC cell proliferation and migration, and induced apoptosis. These effects were enhanced after combined treatment with resveratrol and miR-769-5p mimics. MSI1 was identified as a target of miR-769-5p, and its overexpression attenuated the effects of miR-769-5p mimics on cell proliferation, migration, and apoptosis. Moreover, miR-769-5p overexpression enhanced the inhibitory effects of resveratrol on tumor growth in vivo. Resveratrol inhibited colorectal cancer cell tumor properties by activating the miR-769-5p/MSI1 pathway.</p>","PeriodicalId":18865,"journal":{"name":"Molecular Biotechnology","volume":" ","pages":"1893-1907"},"PeriodicalIF":2.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141071540","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Increased Immune Infiltration and Improved Prognosis of Head and Neck Squamous Cell Carcinoma Associated with Reduced Ancient Ubiquitous Protein 1 Gene Expression.","authors":"Yi Wang, Qian Wu, Xiao Wei, Gang Huang, Guangyong Feng, Hui Xu, Xiaoxia Gou","doi":"10.1007/s12033-024-01161-2","DOIUrl":"10.1007/s12033-024-01161-2","url":null,"abstract":"<p><p>This study aimed to explore the molecular mechanism underlying the prognostic role of ancient ubiquitous protein 1 (AUP1) in head and neck squamous cell carcinoma (HNSCC) and its relationship with the tumor immune microenvironment. Various web resources were used to analyze the differential expression of AUP1 and its role in the HNSCC pathogenesis. A nomogram aimed at predicting 1-, 3-, and 5-year survival rates was developed based on the patient's clinicopathological characteristics and AUP1 expression pattern. Several algorithms and analytical tools were used to explore the correlation between AUP1 expression and sensitivity to immune checkpoint gene therapy by evaluating infiltrating immune cells in patients with HNSCC. Higher AUP1 mRNA and protein expression levels were observed in most tumors and HNSCC than in the normal tissues. High AUP1 expression was an independent predictive risk factor for the overall survival of patients as it was closely associated with the patients' T, M, clinical, and pathological stages and lymphovascular invasion in HNSCC. In conclusion, AUP1 is involved in the occurrence and progression of HNSCC, may be used as an independent prognostic factor in patients with HNSCC, and could serve as a potential intervention target to improve immunotherapy sensitivity in HNSCC.</p>","PeriodicalId":18865,"journal":{"name":"Molecular Biotechnology","volume":" ","pages":"1826-1842"},"PeriodicalIF":2.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141306335","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Potential Impact of Climate Change-Induced Alterations on Pyroptotic Cell Death in Animal Cells: A Review.","authors":"Caglar Berkel","doi":"10.1007/s12033-024-01182-x","DOIUrl":"10.1007/s12033-024-01182-x","url":null,"abstract":"<p><p>Climate change-induced alterations in temperature variation, ozone exposure, water salinity and acidification, and hypoxia might influence immunity and thus survival in diverse groups of animals from fish to mammals. Pyroptosis is a type of lytic pro-inflammatory programmed cell death, which participates in the innate immune response, and is involved in multiple diseases characterized by inflammation and cell death, mostly studied in human cells. Diverse extrinsic factors can induce pyroptosis, leading to the extracellular release of pro-inflammatory molecules such as IL-18. Climate change-related factors, either directly or indirectly, can also promote animal cell death via different regulated mechanisms, impacting organismal fitness. However, pyroptosis has been relatively less studied in this context compared to another cell death process, apoptosis. This review covers previous research pointing to the potential impact of climate change, through various abiotic stressors, on pyroptotic cell death in different animal cells in various contexts. It was proposed that temperature, ozone exposure, water salinity, water acidification and hypoxia have the potential to induce pyroptotic cell death in animal cells and promote inflammation, and that these pyroptotic events should be better understood to be able to mitigate the adverse effects of climate change on animal physiology and health. This is of high importance considering the increasing frequency, intensity and duration of climate-based changes in these environmental parameters, and the critical function of pyroptosis in immune responses of animals and in their predisposition to multiple diseases including cancer. Furthermore, the need for further mechanistic studies showing the more direct impact of climate change-induced environmental alterations on pyroptotic cell death in animals at the organismal level was highlighted. A complete picture of the association between climate change and pyroptosis in animals will be also highly valuable in terms of ecological and clinical applications, and it requires an interdisciplinary approach. SIGNIFICANCE: Climate change-induced alterations might influence animal physiology. Pyroptosis is a form of cell death with pro-inflammatory characteristics. Previous research suggests that temperature variation, ozone exposure, water salinity and acidification, and hypoxia might have the potential to contribute to pyroptotic cell death in certain cell types and contexts. Climate change-induced pyroptotic cell death should be better understood to be able to mitigate the adverse effects of climate change on animal health.</p>","PeriodicalId":18865,"journal":{"name":"Molecular Biotechnology","volume":" ","pages":"1784-1799"},"PeriodicalIF":2.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140922438","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Marine-Derived Cytosine Arabinoside (Ara-C) Inhibits Biofilm Formation by Inhibiting PEL Operon Proteins (Pel A and Pel B) of Pseudomonas aeruginosa: An In Silico Approach.","authors":"Susmita Datta, Vishal Singh, Soma Nag, Dijendra Nath Roy","doi":"10.1007/s12033-024-01169-8","DOIUrl":"10.1007/s12033-024-01169-8","url":null,"abstract":"<p><p>Pseudomonas aeruginosa (P. aeruginosa) is a gram-negative biofilm-forming opportunistic human pathogen whose vital mechanism is biofilm formation for better survival. PelA and PelB proteins of the PEL operon are essential for bacterial-synthesized pellicle polysaccharide (PEL), which is a vital structural component of the biofilm. It helps in adherence of biofilm on the surface and maintenance of cell-to-cell interactions and with other matrix components. Here, in-silico molecular docking and simulation studies were performed against PelA and PelB using ten natural bioactive compounds, individually [podocarpic acids, ferruginol, scopadulcic acid B, pisiferic acid, metachromin A, Cytarabine (cytosine arabinoside; Ara-C), ursolic acid, oleanolic acid, maslinic acid, and betulinic acid], those have already been established as anti-infectious compounds. The results obtained from AutoDock and Glide-Schordinger stated that a marine-derived cytosine arabinoside (Ara-C) among the ten compounds binds active sites of PelA and PelB, exhibiting strong binding affinity [Trp224 (hydrogen), Ser219 (polar), Val234 (hydrophobic) for PelA; Leu365 and Glu389 (hydrogen), Gln366 (polar) for PelB] with high negative binding energy - 5.518 kcal/mol and - 6.056 kcal/mol, respectively. The molecular dynamic and simulation studies for 100 ns showed the MMGBSA binding energy scores are - 16.4 kcal/mol (Ara-C with PelA), and - 22.25 kcal/mol (Ara-C with PelB). Further, ADME/T studies indicate the IC₅₀ values of AraC are 6.10 mM for PelA and 18.78 mM for PelB, which is a comparatively very low dose. The zero violation of Lipinski's Rule of Five further established that Ara-C is a good candidate for drug development. Thus, Ara-C could be considered a potent anti-biofilm compound against PEL operon-dependent biofilm formation of P. aeruginosa.</p>","PeriodicalId":18865,"journal":{"name":"Molecular Biotechnology","volume":" ","pages":"1924-1938"},"PeriodicalIF":2.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140912566","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"METTL3 Promotes OSCC Progression by Down-Regulating WEE1 in a m6A-YTHDF2-Dependent Manner.","authors":"Yongxu Su, Yanjia Hu, Binbin Qu, Rongchang Lei, Ge Guo","doi":"10.1007/s12033-024-01165-y","DOIUrl":"10.1007/s12033-024-01165-y","url":null,"abstract":"<p><p>Oral squamous cell carcinoma (OSCC) is a common and highly lethal epithelial cancer. This study aimed to confirm the role of METTL3 in promoting OSCC and investigate its specific underlying mechanisms. Expression of the METTL3, YTH domain-containing family 2 (YTHDF2), and WEE1 were examined in normal oral epithelial cells and OSCC cells. Cell functions were examined after overexpressing WEE1 in OSCC cells. MeRIP-qPCR analysis was used to detect WEE1 m6A levels in HOK, SCC25, and CAL27 cells. WEE1 and its m6A levels were evaluated in OSCC cells by knocking down METTL3/YTHDF2, assessing the interaction between METTL3/YTHDF2 and WEE1. The impact of METTL3 and YTHDF2 downregulation on WEE1 mRNA stability was also investigated. The tumor weight and volume in a nude mouse model of OSCC after overexpression of WEE1 and YTHDF2 were measured. Expression of Ki-67 and WEE1 in OSCC tissue was detected using immunohistochemistry. Compared to normal oral epithelial cells, METTL3 and YTHDF2 were upregulated in OSCC cells, while WEE1 was downregulated, and there was a negative correlation between WEE1 and METTL3/YTHDF2 expression. WEE1 overexpression inhibited proliferation, invasion, and migration while promoting apoptosis in OSCC cells. METTL3 and YTHDF2 bound to WEE1 mRNA. METTL3/YTHDF2 knockdown increased WEE1 levels and WEE1 mRNA stability. METTL3 inhibition reduced WEE1 m6A levels. Inhibition of METTL3 weakened the interaction between YTHDF2 and WEE1 mRNA. In vivo, overexpression of WEE1 suppressed OSCC development, which was reversed by overexpression of YTHDF2. METTL3 facilitates the progression of OSCC through m6A-YTHDF2-dependent downregulation of WEE1.</p>","PeriodicalId":18865,"journal":{"name":"Molecular Biotechnology","volume":" ","pages":"1867-1879"},"PeriodicalIF":2.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140922476","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Novel Neutrophil Extracellular Trap Signature Predicts Patient Chemotherapy Resistance and Prognosis in Lung Adenocarcinoma.","authors":"Long Xing, Shuangli Wu, Shiyue Xue, Xingya Li","doi":"10.1007/s12033-024-01170-1","DOIUrl":"10.1007/s12033-024-01170-1","url":null,"abstract":"<p><p>Chemoresistance is a key obstacle in the long-term survival of patients with locally and advanced lung adenocarcinoma (LUAD). This study used bioinformatic analysis to reveal the chemoresistance of gene-neutrophil extracellular traps (NETs) associated with LUAD. RNA sequencing data and LUAD expression patterns were obtained from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, respectively. The GeneCards database was used to identify NETosis-related genes (NRGs). To identify hub genes with significant and consistent expression, differential analysis was performed using the TCGA-LUAD and GEO datasets. LUAD subtypes were determined based on these hub genes, followed by prognostic analysis. Immunological scoring and infiltration analysis were conducted using NETosis scores (N-scores) derived from the TCGA-LUAD dataset. A clinical prognostic model was established and analyzed, and its clinical applications explored. Twenty-two hub genes were identified, and consensus clustering was used to identify two subgroups based on their expression levels. The Kaplan-Meier (KM) curves demonstrated statistically significant differences in prognosis between the two LUAD subtypes. Based on the median score, patients were further divided into high and low N-score groups, and KM curves showed that the N-scores were more precise at predicting the prognosis of patients with LUAD for overall survival (OS). Immunological infiltration analysis revealed significant differences in the abundances of 10 immune cell infiltrates between the high and low N-score groups. Risk scores indicated significant differences in prognosis between the two extreme score groups. The risk scores for the prognostic model also indicated significant differences between the two groups. The results provide new insights into NETosis-related differentially expressed genes (NRDEGs) associated with chemotherapy resistance in patients with LUAD. The established prognostic model is promising and could help with clinical applications to evaluate patient survival and therapeutic efficiency.</p>","PeriodicalId":18865,"journal":{"name":"Molecular Biotechnology","volume":" ","pages":"1939-1957"},"PeriodicalIF":2.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140907612","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}