Journal of Cancer最新文献

{"title":"Metabolomics-based combination of GH and NVB in the treatment of NSCLC lung cancer recurrence.","authors":"Xinxin Li, Fengfei Chen, Rui Yang, Zhaohui Song, Xiaohui Ma, Li Sun, Shengtao Yuan","doi":"10.7150/jca.102722","DOIUrl":"10.7150/jca.102722","url":null,"abstract":"<p><p>Lung cancer is one of the most harmful cancers in the world, endangering the lives and health of many people. Although there are various methods to treat lung cancer at present, but lung cancer is asymptomatic in the early stages and has a high recurrence rate after late treatment which make it difficult to cure with conventional treatments. Drug combinations for the treatment of lung cancer have been used in many clinical studies. In this study, we constructed a recurrence model of Non-Small Cell Lung Cancer (NSCLC) lung cancer and used a combination of Ginsenoside H dripping pills (GH) and vinorelbine (NVB) to treat the recurrence of lung cancer. The results showed that the inhibition rate of the combined treatment of GH and NVB is 74.81% which is significantly higher than the therapeutic effect of separate use. We also used GC-TOF/MS-based metabolomics to identify differentially abundant metabolites in relapse models and explore biomarker trends. We found that there are 12 metabolite differences in the abundance of metabolites between the treatment groups (GH group, NVB group and GH-NVB group) and the model group, such as glucose 6-phosphate, palmitoleic acid, linoleic acid, guanine, allantoic acid. The differences in these metabolites involve glucose and lipid metabolism, amino acid metabolism, and purine metabolism. We further analyzed the changes in the content of these metabolites and found that the combined use of GH and NVB can regulate purine metabolism, folate synthesis, and thiamine metabolism, ultimately reducing the abnormal increase in alkaline phosphatase (AP). This study provides a method for the treatment of lung cancer and some biomarkers for the detection of lung cancer.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"16 1","pages":"265-278"},"PeriodicalIF":3.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11660129/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142914884","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacological Profiling of <i>Calotropis Procera</i> and <i>Rhazya Stricta</i>: Unraveling the Antibacterial and Anti-Cancer Potential of Chemically Active Metabolites.","authors":"Sahar S Alghamdi, Allulu Y Alturki, Rizwan Ali, Rasha S Suliman, Afrah E Mohammed, Atheer Al Dairem, Zeyad I Alehaideb, Raghad A Alshafi, Sara A Alghashem, Ishrat Rahman","doi":"10.7150/jca.96848","DOIUrl":"10.7150/jca.96848","url":null,"abstract":"<p><p><b>Background:</b> The increasing prevalence of cancer and bacterial resistance necessitates more effective anti-cancer and anti-bacterial treatments. This study explores the potential of medicinal plants, specifically <i>Calotropis procera</i> (<i>C. procera</i>) and <i>Rhazya stricta</i> (<i>R. stricta</i>), in addressing this need, aiming to uncover new therapeutic interventions. <b>Methods:</b> Various extraction methods for the leaves of <i>C. procera</i> and <i>R. stricta</i> were employed to investigate the anti-bacterial and anti-cancer properties of these herbs. For anti-bacterial testing, extracts were prepared using water, chloroform, and ethyl acetate, and their activity against methicillin-resistant <i>Staphylococcus aureus</i> (<i>S. aureus</i>) (MRSA) and <i>Escherichia coli</i> (<i>E. coli</i>) was assessed. The anti-cancer potential was evaluated through MTT cytotoxicity assays on various cancer cell lines and further testing using high-content imaging (HCI)-Apoptosis Assay and the ApoTox-GloTM Triplex Assay. Liquid chromatography-mass spectrometry (LC-MS) was used to identify the secondary metabolites of <i>C. procera</i>, and computational predictions were performed to assess the activity of these metabolites. <b>Results:</b> The leaf extracts of both <i>C. procera</i> and <i>R. stricta</i> demonstrated antibacterial activity against <i>S. aureus</i> and <i>E. coli</i>. The <i>C. procera</i> ethyl acetate extract exhibited potent anti-cancer effects on several cancer cell lines. The research also revealed a dose-dependent induction of apoptosis and a decline in cell viability. Computational predictions suggested the identified metabolites were active as nuclear receptor ligands and enzyme inhibitors, with good oral bioavailability. Most metabolites were found to be immunologic and cytotoxic, except for proceragenin and calotropone, which were determined to be non-cardiotoxic. <b>Conclusion:</b> The study's findings demonstrate the remarkable cytotoxic and antibacterial effects of <i>C. procera</i> extracts prepared using ethyl acetate. These results pave the way for further <i>in vitro</i> studies to explore the full potential of these extracts and highlight the presence of chemically active metabolites in <i>C. procera</i>, which hold promise as lead molecules for the development of novel therapies targeting bacterial infections and cancer while minimizing potential side effects.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"16 1","pages":"12-33"},"PeriodicalIF":3.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11660137/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142914888","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Screening of Hub Genes and Therapeutic Drugs in Cervical Cancer Using Integrated Bioinformatics Analysis.","authors":"Ziruo Talihati, Kayisaier Abudurousuli, Sendaer Hailati, Mengyuan Han, Muhadaisi Nuer, Nawaz Khan, Nulibiya Maihemuti, Jimilihan Simayi, Weiyi Zhang, Wenting Zhou","doi":"10.7150/jca.87027","DOIUrl":"10.7150/jca.87027","url":null,"abstract":"<p><p><b>Objective:</b> Cervical cancer (CC) is one of the most common female malignancies globally. The current study aimed to identify novel hub genes associated with traditional Chinese herbs and investigate their underlying mechanisms using bioinformatics analysis combined with experimental verification. <b>Methods:</b> Expression profiling of 22 samples was obtained from the GEO database. Differential expression analysis was performed using the limma package in R. The Chinese herbal formulas related to the treatment of cervical cancer were searched in the TCMIP database using the keyword \"cervical cancer\". disease targets associated with cervical cancer were retrieved based on six databases, including the DisGeNet, Genecards, CTD, OMIM, GEO, and TTD databases. The database STRING and Cytoscape were utilized to determine candidate hub genes. The hub genes were further investigated using UALCAN, Kaplan‒Meier-plotter databases, Human Protein Atlas, and the AutoDock Vina software. The results of network pharmacology analysis were verified by <i>in vitro</i> experiments. <b>Results:</b> By intersecting the disease targets with the drug targets, we obtained 49 possible therapeutic targets for cervical cancer. Afterward, we analyzed 49 therapeutic targets using the STRING database and the cytoHubba plugin and eventually obtained six hub genes, MYC, HIF1A, TP53, STAT3, CCND1, and AKT1. The final hub genes were indicated to have significant prognostic relevance in cervical cancer. In addition, the six hub genes were molecularly docked with traditional Chinese medicine for cancer, including quercetin, licochalcone a, nobiletin, naringin, and kaempferol. The results also showed that traditional Chinese medicine could decrease the mRNA and protein expressions, suggesting that quercetin, licochalcone a, nobiletin, naringin, and kaempferol can treat CC by inducing cell apoptosis. <b>Conclusions:</b> We identify six genes that can be therapeutic targets for cervical cancer, confirm that quercetin, licochalcone a, nobiletin, naringin, and kaempferol exert therapeutic effects on cervical cancer by regulating apoptosis pathways through <i>in vitro</i> experiments, and provide insights into the molecular mechanisms of the impact of traditional Chinese medicine in cancer treatment.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"16 1","pages":"92-109"},"PeriodicalIF":3.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11660142/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142914890","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The causal association between neutrophil counts and the risk of lung cancer: a Mendelian randomization study.","authors":"Yunzhao Ren, Zhaojun Lu, Xiaoxue Liu","doi":"10.7150/jca.100884","DOIUrl":"10.7150/jca.100884","url":null,"abstract":"<p><p>An increased neutrophil level in the blood is considered a risk factor for lung cancer (LC). However, establishment of causality is hampered by the inconsistent findings of observational studies. This study aimed to explore the causal association between neutrophil counts (NC) and LC risk in two populations via two-sample mendelian randomization (MR) analysis. The inverse-variance weighted method was used to evaluate causality. Sensitivity analyses were conducted to examine the stability of the results. Bidirectional MR analysis was performed to check reverse causality, and a multivariable MR analysis was conducted to adjust for confounding factors. The results revealed a significant causal relationship between NC and LC (OR=1.027, 95% CI: 1.005-1.050, <i>P=</i>0.017) in the European population but not in the East Asian population (OR=1.223, 95% CI: 0.999-1.497; <i>P</i>=0.052). The sensitivity analysis confirmed the robustness of the results, and we excluded potential reverse causation. A multivariable analysis demonstrated that a significant genetic association (OR=1.044, 95% CI: 1.002-1.088, <i>P</i>=0.042) remained after controlling for smoking. Our findings provide information on the causal relationship between NC and LC, and highlight the objective differences in genetic variation among ethnicities.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"16 1","pages":"331-338"},"PeriodicalIF":3.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11660127/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142914904","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Raddeanin A (RA) Inhibited EMT and Stemness in Glioblastoma via downregulating Skp2.","authors":"Weiqiang Jia, Yanling Zhang, Qiang Zhao, Min Gong, Yang Cao, Jia Liu, Shuang Luo","doi":"10.7150/jca.95266","DOIUrl":"10.7150/jca.95266","url":null,"abstract":"<p><p><b>Background:</b> Glioblastoma (GBM), notorious for its poor prognosis, stands as a formidable challenge within the central nervous system tumor category, primarily due to its intricate pathology that encompasses stemness and the epithelial-mesenchymal transition (EMT). The ubiquity of S phase kinase-associated protein 2 (Skp2) overexpression in GBM, a protein implicated in both EMT and stemness traits, correlates with increased drug resistance, elevated tumor grades, and adverse outcomes. This investigation delves into the impact of Raddeanin A (RA), a triterpenoid compound extracted from Anemone raddeana Regel, on GBM, with a special focus on its influence over Skp2 expression levels. <b>Method:</b> The study assessed RA's influence on GBM cell lines U87 and U251 via CCK-8 and colony formation assays to gauge cell proliferation, alongside Transwell assays for evaluating migration and invasion capabilities. mRNA expression was detected by RT-PCR. Protein expression alterations were examined through western blotting and immunofluorescence techniques. The therapeutic potential of RA <i>in vivo</i> was also evaluated using subcutaneous and intracranial xenograft model in mice, developed using U87 cells. The molecular docking experiment was performed to evaluate the binding of RA to Skp2. <b>Results:</b> RA markedly curtailed the proliferation of U87 and U251 cells in a concentration-dependent manner, alongside diminishing sphere formation in glioblastoma stem-like cells (GSCs). A significant suppression of Skp2 expression was observed in both cell lines and GSCs following RA treatment. This reduction in Skp2 was associated with a decrease in stemness markers (Sox2, Nestin) and the inhibition of EMT markers (Vimentin, N-cadherin, Snail). Moreover, Skp2 overexpression was found to mitigate RA's suppressive effects on EMT and stemness, highlighting Skp2's crucial role in these processes. The <i>in vivo</i> experiments supported these findings, indicating that RA not only thwarted tumor growth but also substantially lowered the expression of Skp2, EMT markers, and stemness indicators. Additionally, molecular docking experiments demonstrated that RA exhibits a notable binding affinity to Skp2. <b>Conclusion:</b> This study elucidates RA's significant antitumor efficacy against GBM <i>in vitro</i> and <i>in vivo</i> by targeting pathways linked to stemness and EMT, chiefly via the downregulation of Skp2. These findings underscore RA's therapeutic promise in GBM management, offering insights into its mechanism of action and laying the groundwork for subsequent clinical investigations.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"16 1","pages":"44-54"},"PeriodicalIF":3.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11660117/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142914889","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A novel EMT-related risk score model for Uveal melanoma based on ZNF667-AS1 and AP005121.1.","authors":"Fan Yang, Yue Ren, Dongmei Qi, Xi Liu, Jing Xie","doi":"10.7150/jca.101823","DOIUrl":"10.7150/jca.101823","url":null,"abstract":"<p><p>Uveal melanoma (UM) has emerged as one of the most common primary intraocular malignant tumors worldwide. Long non-coding RNAs (lncRNAs) are increasingly recognized as decisive factors in the progression and metastasis of UM, involving in epithelial-mesenchymal transition (EMT) of UM. We conducted a comprehensive analysis of lncRNAs closely associated with EMT-related genes in the TCGA UM cohort, identifying 961 EMT-related lncRNAs. Through univariate COX analysis, we identified 9 survival-related EMT-related lncRNAs (sER-lncRNAs), further establishing an EMT-related risk scoring model (ER-RSM) with two sER-lncRNAs (ZNF667-AS1 and AP005121.1) identified by multivariate COX analysis. Through this ER-RSM, low-risk UM patients achieved better overall survival than high-risk UM patients. AP005121.1 was positively correlated with higher stage and M staging in UM patients, while ZNF667-AS1 was positively correlated with earlier stage, T, and M staging in UM patients. <i>In vitro</i>, AP005121.1 expression was higher in UM tumor tissues and cell lines than in adjacent normal tissues and human retinal pigment epithelial cells, whereas ZNF667-AS1 expression showed the opposite pattern. siR-AP005121.1 significantly inhibited migration and invasion ability of UM cells and suppressed the EMT pathway, while siR-ZNF667-AS1 promoted migration and invasion of UM cells and activated the EMT pathway. In this study, we screened sER-lncRNAs and constructed an ER-RSM to investigate the relationship between sER-lncRNAs and prognosis and clinical staging of UM. Additionally, we validated the expression of sER-lncRNAs in UM clinical samples and cell lines. The ER-RSM may provide potential key insights for the diagnosis and therapeutic intervention of UM patients.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"16 2","pages":"460-469"},"PeriodicalIF":3.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11685695/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142914940","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigating causal relationships of blood and urine biomarkers with urological cancer risks: a mendelian randomization study and colocalization analyses.","authors":"Jian Li, Bing Yang, Lei Guo, Wenqi Huang, Qiong Hu, Hongting Yan, Rong Tan, Dongxin Tang","doi":"10.7150/jca.103669","DOIUrl":"https://doi.org/10.7150/jca.103669","url":null,"abstract":"<p><p><b>Background:</b> Establishing the causal links between biomarkers and cancer enhances understanding of risk factors and facilitates the discovery of therapeutic targets. To this end, we used Mendelian randomization (MR) and colocalization analysis to explore the causal relationship of blood and urinary biomarkers (BUBs) with urological cancers (UCs). <b>Methods:</b> First, we used a two-sample MR study to explore the causal relationship between 33 BUBs and 4 UCs, while we performed reverse Mendelian randomization. After Bonferroni correction, for BUB and UC with significant causality we confirmed the direct causality by multivariate MR adjusting for relevant risk factors. We also applied two-step MR analysis to further explore the possible mediators between BUB and UC with significant causality, while colocalization analysis was performed for BUB, UC and possible mediators. Sensitivity analysis were performed to assess the robustness of the results. <b>Results:</b> A two-sample MR study found that there were 8 BUBs of CA, IGF-1, LPA, TP, CRE, BILD, TBIL and NAP with potential causality with some UCs (p<0.05), but after Bonferroni correction only IGF-1 had a significant causality with PCa (OR = 1.14, 95% CI: 1.06-1.23; p=0.0006<0.05/33). Moreover, the causal relationship between IGF-1 and PCa remained significant (P<0.05) after adjusting for relevant risk factors in the multivariate MR study. The two-step MR study found SHBG to be a mediator between IGF-1 and PCa, and the colocalization analysis found that there was a common causal variant (nearby gene TNS3) between IGF-1 and SHBG (PPH4=93.21%), which further confirmed the mediating effect of SHBG. <b>Conclusion:</b> Strong evidence from our study suggests that IGF-1 increases the risk of PCa by decreasing SHBG levels, and in addition some BUBs were found to have a potential causal relationship with UCs.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"16 3","pages":"1020-1031"},"PeriodicalIF":3.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11705052/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142949451","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Causal inference between immune cells and glioblastoma: a bidirectional Mendelian randomization study.","authors":"Shiqiang Hou, Chunjing Jin, Beitian Shi, Yinan Chen, Ning Lin","doi":"10.7150/jca.100519","DOIUrl":"10.7150/jca.100519","url":null,"abstract":"<p><p><b>Background:</b> Glioblastoma (GBM) and immunology are closely related, but its mechanism remains unclear. This study aimed to observe the causal inference between GBM and various immune cells by bidirectional Mendelian randomization (MR) analysis. <b>Methods:</b> We used immune cell and GBM data from the GWAS database. A total of 731 immunophenotypes, including four trait types and seven panels. For bidirectional MR analysis, Inverse Variance Weighted and False Discovery Rate (FDR) were both employed. Sensitivity analysis was also performed to make sure the results were reliable. <b>Results:</b> According to FDR, seven immunophenotypes associated with GBM risk: CD33br HLA DR+ AC (FDR = 0.009), CD38 on PB/PC (FDR = 0.046), CD66b on CD66b++ myeloid cell (FDR = 0.019), CD3 on CD39+ resting Treg (FDR = 0.009), HVEM on CM CD8br (FDR = 0.050), CD45 on CD33br HLA DR+ CD14dim (FDR = 0.027), and CD86 on CD62L+ myeloid DC (FDR = 0.048). In reverse MR analysis, GBM was found to be strongly associated with nine immunophenotypes based on FDR: BAFF-R on CD24+ CD27+ (FDR = 0.033), BAFF-R on IgD+ CD38- (FDR = 0.036), BAFF-R on IgD-CD38br (FDR = 0.039), BAFF-R on unsw mem (FDR = 0.048), BAFF-R on CD20- (FDR=0.012), HVEM on EM CD8br (FDR=0.036), CCR2 on myeloid DC (FDR = 0.035), CD45 on CD33-HLA DR+ (FDR = 0.004), and CD34 on HSC (FDR = 0.035). <b>Conclusion:</b> The current study confirmed the causal inference between 16 different immunophenotypes and GBM using genetic tools, providing an important foundation and guide for future immunological research and immunotherapy of GBM.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"16 1","pages":"171-181"},"PeriodicalIF":3.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11660118/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142914827","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deciphering the Prognostic Landscape of Esophageal Adenocarcinoma: A PANoptosis-Related Gene Signature.","authors":"Haijing Fu, Mengyan Liu, Huiyu Li, Li Yu, Haizhu Song, Xiaoyuan Chu, Wei Bao","doi":"10.7150/jca.102180","DOIUrl":"10.7150/jca.102180","url":null,"abstract":"&lt;p&gt;&lt;p&gt;&lt;b&gt;Backgrounds:&lt;/b&gt; Esophageal adenocarcinoma (EAC) remains a challenging malignancy with low survival rates despite advances in treatment. Understanding the molecular mechanisms and identifying reliable prognostic markers are crucial for improving clinical outcomes. &lt;b&gt;Methods:&lt;/b&gt; We conducted a comprehensive bioinformatics analysis utilizing TCGA, GTEx, and GEO datasets to identify PANoptosis-related genes (PRGs) associated with EAC. From this analysis, we developed a prognostic risk score model based on 8 prognostically significant differentially expressed PRGs. This model was externally validated and compared with traditional staging methods. Functional analyses, including gene expression profiling, pathway enrichment analysis, and immune infiltration assessment, were conducted to elucidate the biological mechanisms influencing prognosis. To identify PANoptosis-related hub genes, we employed Weighted Gene Co-expression Network Analysis (WGCNA). The expression profiles of the hub gene were examined using reverse transcription-quantitative PCR (RT-qPCR) and western blotting. Furthermore, the effects of the hub genes knockdown or overexpression on EAC cell behavior were verified through in vitro experiments, including cell counting kit (CCK)-8, transwell and wound healing assay. &lt;b&gt;Results:&lt;/b&gt; The prognostic risk score model effectively predicts patient outcomes, supported by principal component analysis (PCA) and receiver operating characteristic (ROC) curves. The resulting prognostic nomogram, which integrates clinical features and the risk score, outperforms traditional staging systems, offering enhanced predictive accuracy. WGCNA identified gene modules significantly correlated with EAC clinical traits, highlighting the biological relevance of these genes to disease progression. Functional enrichment analyses shed light on significant biological processes and pathways associated with high-risk EAC, including lipid metabolism and hormone transport. Immune infiltration analysis revealed distinct immune profiles between risk groups, pinpointing potential immunotherapeutic targets. Furthermore, drug sensitivity analysis indicated specific compounds that may be more effective in high-risk groups. Notably, MMP12 emerged as a key mediator and further experimental results revealed that the lower the degree of cell differentiation, the higher the expression level of MMP12 in EAC. The knockdown of MMP12 significantly inhibited cell proliferation and migration. &lt;b&gt;Conclusions:&lt;/b&gt; Our findings present a validated risk scoring model and prognostic nomogram as valuable tools for predicting patient outcomes and guiding personalized treatments in EAC. This study underscores the potential of molecular clustering and PANoptosis-based prognostic features in predicting patient survival and understanding the tumor microenvironment's complexity, especially the metabolic and immune profiles, in EAC. These insights enhance our understanding of PANoptosis i","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"16 1","pages":"183-200"},"PeriodicalIF":3.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11660136/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142914835","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Demethylzeylasteral inhibits oxidative phosphorylation complex biogenesis by targeting LRPPRC in lung cancer.","authors":"Lina Wang, Wei Zhou, Wenxi Wang, Yuxin Liang, Qiqi Xue, Zhen Zhang, Jinghe Yuan, Xiaohong Fang","doi":"10.7150/jca.92797","DOIUrl":"10.7150/jca.92797","url":null,"abstract":"<p><p>Targeted inhibition of mitochondrial oxidative phosphorylation (OXPHOS) complex generation is an emerging and promising cancer treatment strategy, but limited targets and specific inhibitors have been reported. Leucine-rich pentatricopeptide repeat-containing protein (LRPPRC) is an atypical RNA-binding protein that regulates the stability of all 13 mitochondrial DNA-encoded mRNA (mt-mRNA) and thus participates in the synthesis of the OXPHOS complex. LRPPRC is also a prospective therapeutic target for lung adenocarcinoma, serving as a promising target for OXPHOS inhibition. In this study, we identified Demethylzeylasteral (T-96), a small molecule extracted from the Chinese herb <i>Tripterygium wilfordii</i> Hook. f., as a novel inhibitor of LRPPRC. T-96 directly bound to the RNA-binding domain of LRPPRC, inhibiting its interaction with mt-mRNA. This led to instability in both mt-mRNA and LRPPRC protein. Treatment with T-96 significantly reduced the mRNA and protein levels of the OXPHOS complex. As a consequence of LRPPRC inhibition, T-96 treatment induced a defect in the synthesis of the OXPHOS complex, inhibiting mitochondrial aerobic respiration and ATP synthesis. Moreover, T-96 exhibited potent antitumor activity for lung adenocarcinoma <i>in vitro</i> and <i>in vivo</i>, and the antitumor effect of T-96 was dependent on LRPPRC expression. In conclusion, this study not only identified the first traditional Chinese medicine monomer inhibitor against OXPHOS complex biosynthesis as well as a novel target of Demethylzeylasteral, but also shed light on the unique antitumor mechanism of bioactive compounds derived from traditional Chinese medicine.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"16 1","pages":"227-240"},"PeriodicalIF":3.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11660126/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142914850","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}