International Journal of Medical Sciences最新文献

{"title":"Erratum: Overexpression of ATAD2 indicates Poor Prognosis in Oral Squamous Cell Carcinoma: Erratum.","authors":"Xiao-Long Wang, Shuo Wang, Zhi-Zhong Wu, Qi-Chao Yang, Hao Li, Hong-Gang Xiong, Shu-Cheng Wan, Zhi-Jun Sun","doi":"10.7150/ijms.112159","DOIUrl":"https://doi.org/10.7150/ijms.112159","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.7150/ijms.46809.].</p>","PeriodicalId":14031,"journal":{"name":"International Journal of Medical Sciences","volume":"22 8","pages":"1978"},"PeriodicalIF":3.2,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11983315/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143980430","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":"Integrating Single-Cell and Bulk RNA Sequencing Data to Explore Sphingolipid Metabolism Molecular Signatures in Ovarian Cancer Prognosis: an Original Study.","authors":"Xu Huang, Xiaoyu Li, Wulin Shan, Yingyu Dou, Qiongli Yu, Yao Chen, Zengying Wang, Haomin Zhang, Yumeng Wang, Xiaofei Lu, Wenju Peng, Bairong Xia","doi":"10.7150/ijms.107391","DOIUrl":"https://doi.org/10.7150/ijms.107391","url":null,"abstract":"<p><p><b>Background:</b> Ovarian cancer (OC) is the deadliest malignant tumor in the female reproductive system. Sphingolipid metabolism (SM) is crucial for cellular function and has been linked to OC progression. Dysregulation of sphingolipid pathways contributes to tumor growth, chemoresistance, and metastasis in OC. Currently, investigations into the relationship between sphingolipid-related genes (SRGs) and OC prognosis in their initial stages. Our study aimed to develop a novel molecular subtyping based on SRGs and construct a signature to predict the prognosis of patients with OC, immune cell infiltration characteristics, and chemotherapy sensitivity. <b>Methods:</b> Bulk and single-cell RNA-sequencing data of OC was analyzed primarily from the TCGA and GEO databases. The gene set related to the sphingolipid pathway (hsa00600) was selected from the SM pathway, and the enrichment of SRGs was analyzed in the annotated single-cell sequencing data. The Scanpy function was used to score the gene features of each cell and further identify differentially expressed genes. By intersecting with the genes most closely related to SM activity identified through Weighted Gene Co-expression Network Analysis (WGCNA) based on bulk RNA sequencing data, and after performing univariate COX, multivariate COX and LASSO regression, three SRGs were identified. Subsequently, the SRGs-related prognostic signature was constructed. The analysis was further extended to clinical feature correlation, GSEA, tumor microenvironment (TME) analysis and chemotherapy sensitivity analysis. Finally, the expression and function of the key gene GBP5 in the model were validated through <i>in vitro</i> experiments. <b>Results:</b> Compared to other sites, SRG scores were highest in ascites, and among different cell types, SRG scores were highest in T cells. By integrating scRNA-seq and bulk RNA-seq analysis, three SRGs (C5AR1, GBP5, and MARCHF3) were ultimately selected to develop a prognostic model for SRGs. In this model, patients with higher risk scores had shorter overall survival, which was validated in the testing cohort. Immune infiltration analysis revealed that the risk score was negatively correlated with the abundance of CD8+ T cell infiltration and positively correlated with the abundance of M2 macrophage infiltration. Chemotherapy sensitivity analysis showed that the high-risk group exhibited increased resistance to Oxaliplatin, Gemcitabine, and Sorafenib. <i>In vitro</i>, we demonstrated that knockdown of the protective gene GBP5 in HEYA8 and SKOV3 cells enhanced cell viability, proliferation, and invasiveness, reduced apoptosis, and increased IC50 values for chemotherapy drugs. <b>Conclusion:</b> Our model effectively identifies high-risk patients and provides a reference for prognosis prediction using SRG signature. Moreover, hub gene GBP5 acts as a tumor inhibitory factor and regulates the chemosensitivity of oxaliplatin, gemcitabine, and sorafenib in OC.</p>","PeriodicalId":14031,"journal":{"name":"International Journal of Medical Sciences","volume":"22 8","pages":"1958-1977"},"PeriodicalIF":3.2,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11983299/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144009576","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":"How telomere maintenance affects endometriosis development: a preliminary study.","authors":"Xiaoling Zhao, Weimin Kong, Dan Luo, Yunkai Xie, He Zhang","doi":"10.7150/ijms.102646","DOIUrl":"https://doi.org/10.7150/ijms.102646","url":null,"abstract":"<p><p><b>Background:</b> Endometriosis results in dysmenorrhea, dyspareunia, chronic pelvic pain and infertility in reproductive-age women. However, no effective treatment methods have been applied to the disease, and the pathogenesis of endometriosis is unclear. <b>Purpose:</b> This study was performed to investigate the association between telomere maintenance and endometriosis development. <b>Materials and methods:</b> The telomere length of the postmenopausal endometria, eutopic endometria and their matched ectopic lesions in the proliferative and secretory phases was detected using fluorescence in situ hybridization (FISH) methods, and the effect of telomere length maintenance on the proliferation of endometrial cells derived from endometriotic patients was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay with BIBR1532 treatment. Then all of the telomere maintenance genes were extracted from the Telnet database, and bioinformatics analysis was performed to uncover the role of telomere maintenance genes in endometriosis development. <b>Results:</b> Telomere length was longer in endometriotic patients' eutopic endometria during the proliferative and secretory phases, and treatment with a telomerase inhibitor inhibited the proliferation of epithelial cells and stromal cells. Furthermore, the telomere maintenance genes were enriched in several hormone-related pathways, with several genes differentially expressed between normal endometria and endometria derived from endometriotic patients. The nomogram constructed based on telomere maintenance genes also displayed good predictive value. <b>Conclusions:</b> Telomere maintenance may contribute to the development of endometriosis, with several related genes involved.</p>","PeriodicalId":14031,"journal":{"name":"International Journal of Medical Sciences","volume":"22 8","pages":"1944-1957"},"PeriodicalIF":3.2,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11983314/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143992532","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":"Hematological parameters and major adverse cardiovascular events: a prospective study in a Chinese population involving 2,970 participants.","authors":"Hongna Mu, Xinyue Wang, Xianghui Zhao, Ruiyue Yang, Wenduo Zhang, Hongxia Li, Siming Wang, Fusui Ji, Wenxiang Chen, Jun Dong, Xue Yu","doi":"10.7150/ijms.104118","DOIUrl":"https://doi.org/10.7150/ijms.104118","url":null,"abstract":"<p><p>Hematological parameters are among the most accessible and routinely performed clinical tests. Recent studies have gradually revealed their potential for risk prediction. This study aimed to assess the association between hematological parameters and major adverse cardiovascular events (MACEs) in patients with coronary artery disease. This prospective study included 2,970 Chinese participants who underwent coronary angiography, with hematological and biochemical indicators measured at baseline. MACEs, comprising myocardial infarction, stroke, revascularization, and all-cause mortality, were recorded during follow-up. Univariate and multivariate analyses were conducted to evaluate the relationship between the hematological parameters and MACEs. Over a median follow-up period of 79 months, 474 MACEs were documented. Kaplan-Meier analysis indicated that the participants with lower levels of RBC, PLT, PCT, LYMPH% and BASO%, as well as higher RDW-CV, RDW-SD, MONO% and NEUT%, exhibited reduced survival probability. Multivariate Cox regression analysis identified elevated RDW-CV as a significant risk factor for MACE (T3 HR, 1.292; 95% CI, 1.013-1.647; <i>P</i>=0.039), while lower BASO% demonstrated a protective effect (T3 HR, 0.750, 95 % CI: 0.591-0.953; <i>P</i>=0.018). LYMPH% also showed a significant association with MACEs. Additionally, nonlinear correlations were observed between PLT and PCT and MACEs. In conclusion, RDW-CV, BASO%, PLT, PCT and LYMPH% were closely associated with MACEs and may serve as potential predictors for cardiovascular risk in patients with coronary artery disease.</p>","PeriodicalId":14031,"journal":{"name":"International Journal of Medical Sciences","volume":"22 8","pages":"1924-1935"},"PeriodicalIF":3.2,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11983297/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144005344","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":"FBXW2 inhibits the progression of gastric cancer via promoting β-catenin ubiquitylation.","authors":"Yanshen Kuang, Mu Ke, Weizheng Liu, Fengming Xu","doi":"10.7150/ijms.108501","DOIUrl":"https://doi.org/10.7150/ijms.108501","url":null,"abstract":"<p><p><b>Background:</b> F-box and WD-repeat-containing protein 2 (FBXW2), an E3 ubiquitin ligase, may play a crucial role in tumorigenesis. However, its function in gastric cancer remains unknown. <b>Methods:</b> The expression levels of FBXW2 and β-catenin in gastric cancer samples were analyzed using RT-PCR and immunohistochemistry, with Pearson correlation analysis to assess their relationship. AGS and HGC-27 gastric cancer cells were transfected with sh-FBXW2, and their viability was evaluated using the CCK8 assay, while invasion ability was assessed via the transwell assay. Western blotting was performed to measure the expression levels of FBXW2, β-catenin, GSK3β, and Axin2 in AGS cells. Additionally, a ubiquitination assay was conducted to examine the effect of sh-FBXW2 on β-catenin ubiquitination. Immunoprecipitation was used to determine the potential interaction between FBXW2 and β-catenin. <b>Results:</b> FBXW2 expression was downregulated, whereas β-catenin expression was upregulated in gastric cancer tissues compared to adjacent normal tissues, showing a significant negative correlation (<i>r</i> = -0.52, <i>P</i> < 0.001). Knockdown of FBXW2 (sh-FBXW2) promoted gastric cancer cell viability and invasion while increasing β-catenin expression and reducing GSK3β and Axin2 levels. Furthermore, FBXW2 was found to bind β-catenin and facilitate its ubiquitination, leading to enhanced nuclear translocation of β-catenin. <b>Conclusions:</b> FBXW2 suppresses gastric cancer progression by promoting β-catenin ubiquitination, highlighting its potential as a therapeutic target.</p>","PeriodicalId":14031,"journal":{"name":"International Journal of Medical Sciences","volume":"22 8","pages":"1936-1943"},"PeriodicalIF":3.2,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11983310/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143986512","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":"Predictors of the Fear of COVID-19 in Individuals with Schizophrenia: a Prospective Study.","authors":"Cheng-Fang Yen, Ching-Shu Tsai, Chien-Wen Lin, Ray C Hsiao, Peng-Wei Wang","doi":"10.7150/ijms.106953","DOIUrl":"https://doi.org/10.7150/ijms.106953","url":null,"abstract":"<p><p><b>Purpose:</b> The fear of COVID-19 can result in psychological distress and mental health problems. Individuals with schizophrenia (IWSs) are especially vulnerable to contracting COVID-19. This study with a 1-year follow-up examined whether individual characteristics (sociodemographic characteristics, schizophrenia symptoms, depression, and self-esteem) or factors related to individual-environmental interaction (self-stigma, loneliness, and perceived social support) predicted the level of fear of COVID-19 (FC) among IWSs. <b>Patients and methods:</b> In total, 257 IWSs (out of an initial pool of 300 IWSs) were enrolled, and their baseline data were collected. FC was assessed using the Fear of COVID-19 Scale at 1 year after the onset of the study. The associations of baseline factors with FC 1 year later were analyzed using bivariable and multiple linear regression analysis. <b>Results:</b> Bivariable linear regression results demonstrated that being a woman (<i>p</i> < 0.05), being unemployed (<i>p</i> < 0.05), having depression (<i>p</i> < 0.001), having low self-esteem (<i>p</i> < 0.05), experiencing loneliness (<i>p</i> < 0.01), and having feelings of self-stigma (<i>p</i> < 0.001) significantly predicted FC 1 year later. A multiple linear regression model further indicated that having feelings of self-stigma significantly predicted FC 1 year later (<i>p</i> < 0.01). <b>Conclusion:</b> Clinicians and policymakers should consider the predictors identified in this study when designing interventions to reduce FC among IWSs.</p>","PeriodicalId":14031,"journal":{"name":"International Journal of Medical Sciences","volume":"22 8","pages":"1916-1923"},"PeriodicalIF":3.2,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11983312/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144028258","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":"MUC15 acts as a tumor suppressor gene which correlates with prognosis and immune infiltration in esophageal squamous cell carcinoma.","authors":"Xiang Fei, Ai-Li Wang, Hao Wu, Si-Wei Xing, Lei Chen, Ying Chen, Xue-Jing Lin, Hai-Long Liu, Bin Sun","doi":"10.7150/ijms.108926","DOIUrl":"https://doi.org/10.7150/ijms.108926","url":null,"abstract":"<p><p>Esophageal squamous cell carcinoma (ESCC), as a common malignant tumor of the digestive system, has been a challenge in improving and prolonging the postoperative survival of patients. This study aims to identify novel biomarkers that can guide the clinical diagnosis and treatment by using bioinformatics methods. The RNA-seq data and corresponding clinical data of ESCC were downloaded from the TCGA and GEO database. Weighted co-expression network analysis (WGCNA) was used to identify candidate biomarkers. The LASSO analysis was performed to classify the biomarkers. ROC curve and AUC were used to evaluate the sensitivity and specificity of biomarkers. CIBERSORT was applied to estimate the relative abundances of immune cell types through gene expression profiling. Univariate and multiple Cox regression were performed to screen out prognostic factors. MUC15, which abnormally expressed in different physiological processes and participates in inhibiting or promoting function in different types of tumors, was selected of candidate biomarker. Finally, we validated the expression of MUC15 in ESCC tissues and its inhibitory effect on cell function through <i>in vitro</i> and <i>in vivo</i> experiments. In conclusion, we identified MUC15 could serve as a tumor suppressor gene and may become a promising candidate for individualized clinical diagnosis and treatment of ESCC.</p>","PeriodicalId":14031,"journal":{"name":"International Journal of Medical Sciences","volume":"22 8","pages":"1905-1915"},"PeriodicalIF":3.2,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11983305/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143992569","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":"Mitochondrial Quality Control Systems in Septic AKI: Molecular Mechanisms and Therapeutic Implications.","authors":"Ying Tan, Yue Ouyang, Zisheng Ma, Jianming Huang, Chuhong Tan, Junxiong Qiu, Feng Wu","doi":"10.7150/ijms.107012","DOIUrl":"https://doi.org/10.7150/ijms.107012","url":null,"abstract":"<p><p><b>Objectives:</b> Despite significant advancements in medical treatments, the creation of a successful treatment strategy for acute kidney injury (AKI) remains a pressing concern. Given the well-documented clinical benefits of canagliflozin in renal protection, our research focused on exploring the possible therapeutic benefits of canagliflozin in treating AKI, with a focus on its underlying mechanisms of action. <b>Methods:</b> To induce AKI, we utilized lipopolysaccharide (LPS) in the presence of canagliflozin, allowing us to assess the drug's effects on kidney function and structure. <b>Results:</b> Our results indicate that canagliflozin lowered blood urea nitrogen and serum creatinine concentrations while enhancing tubular architecture in rodents with LPS-triggered septic AKI. It additionally diminished inflammation, oxidative damage, and tubular cell apoptosis. <i>In vitro</i>, canagliflozin maintained mitochondrial functionality in LPS-exposed HK-2 cells by stabilizing membrane potential, reducing ROS generation, and normalizing respiratory chain activity. Its benefits were facilitated through the AMPKα1/PGC1α/NRF1 axis, promoting mitochondrial regeneration. Importantly, blocking this pathway or employing AMPKα1-deficient animals negated canagliflozin's protective effects, highlighting the essential role of AMPKα1 in its kidney-protective mechanisms. <b>Conclusion:</b> Our investigation implies that canagliflozin might represent a viable treatment strategy for septic AKI, operating through the stimulation of the AMPKα1/PGC1α/NRF1 axis to preserve kidney performance and structural integrity. These findings warrant further investigation into the clinical potential of canagliflozin in this context.</p>","PeriodicalId":14031,"journal":{"name":"International Journal of Medical Sciences","volume":"22 8","pages":"1852-1864"},"PeriodicalIF":3.2,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11983313/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144015122","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":"Danshensu Attenuates Palmitic Acid-Induced Activation of Hepatic Stellate Cells by Regulating Pyroptosis.","authors":"Han-Fang Tseng, Huan-Nung Chao, Chih-Hung Lin, Chan-Yen Kuo","doi":"10.7150/ijms.107564","DOIUrl":"https://doi.org/10.7150/ijms.107564","url":null,"abstract":"<p><p><b>Introduction:</b> We focused on examining the role of Danshensu in reducing reactive oxygen species (ROS) production and inhibiting NLRP3 inflammasome activation, which are key factors in liver fibrosis and inflammation. We sought to explore the potential of Danshensu as a therapeutic agent for liver fibrosis by targeting the pyroptosis-inflammasome signaling pathway, providing a basis for developing effective and safer NLRP3 inflammasome inhibitors. This study aimed to investigate whether Danshensu can mitigate palmitic acid (PA)-induced activation of hepatic stellate cells (HSCs) by regulating pyroptosis in HSC-T6 and LX-2 cells. <b>Methods:</b> HSC-T6 and LX-2 cell lines served as the cell models. A 2',7'-dichlorofluorescin diacetate reagent was used to measure ROS production within cells. Cell protein extraction was performed using radioimmunoprecipitation assay lysis buffer. The protein concentration in each sample was measured using a BCA assay kit. Western blot analysis was used with the SDS-polyacrylamide gel electrophoresis system. <b>Results:</b> PA-induced activation of HSC-T6 and LX-2 cells by upregulating alpha-smooth muscle actin, integrin-β1, and connective tissue growth factor. Danshensu mitigated PA-induced ROS accumulation in these cells. Moreover, Danshensu potentially reversed the upregulation of NLRP3, cleaved caspase 1, interleukin-1, GSDME, and ASC in PA-activated LX-2 cells via pyroptosis, suggesting its therapeutic potential. Pyroptosis inhibitor tetramethylthiuram disulfide reversed Danshensu attenuated PA activation of HSC-T6 and LX-2 cells, resulting in a 2-fold increase in alpha-smooth muscle actin, integrin-β1, and connective tissue growth factor. <b>Conclusion:</b> Danshensu effectively attenuates PA-induced HSC activation by reducing ROS production and inhibiting pyroptosis, offering a potential therapeutic strategy for liver fibrosis.</p>","PeriodicalId":14031,"journal":{"name":"International Journal of Medical Sciences","volume":"22 8","pages":"1865-1874"},"PeriodicalIF":3.2,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11983302/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144005342","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":"<i>In Silico</i> Identification of ANKRD22 as a Theragnostic Target for Pancreatic Cancer and Fostamatinib's Therapeutic Potential.","authors":"Huong Thi Luu Kim Huynh, Hendrick Gao-Min Lim, Yuan-Chii Gladys Lee, Thien-Vy Phan, Thanh-Hoa Vo, Chien-Hsin Chen, Alexander T H Wu","doi":"10.7150/ijms.105193","DOIUrl":"https://doi.org/10.7150/ijms.105193","url":null,"abstract":"<p><p>Pancreatic cancer (PC) is one of the most tremendously malignant cancers with a poor prognosis, especially when it advances to metastasis. Besides, PC patients have encountered resistance to recent therapeutic approaches. In recent work, we effectively determined ANKRD22 by re-analyzing RNA-seq datasets from cell lines and human tissues deriving from PC. We demonstrated that ANKRD22 expression was remarkably high in the PC group compared to the normal group at both gene expression and protein levels. ANKRD22 resulted in a worse overall survival (OS) rate of PC patients (HR = 1.7, p = 0.0082). Intriguingly, ANKRD22 was statistically highly expressed in the mutated KRAS group relative to the wildtype group (p < 0.05). Similarly, compared to the wildtype TP53, in the mutated TP53, ANKRD22 also significantly expressed (p < 0.05); their concurrent expression, ANKRD22 and KRAS; ANKRD22 and TP53 exacerbated the survival outcome relative to the co-expression of low ANKRD22 and unaltered genes (p < 0.001; HR > 2.6). We explored the potential pathways and biological processes ANKRD22 might not only contribute to promoting PC, including cell-cycle regulation, E2F1 targets, and apoptosis but also foster the dissemination of PC by involve in invasion and migration processes. In the investigation of drugs that might target ANKRD22, we figured out fostamatinib. Molecular docking and molecular dynamic simulation (MDs) techniques provided extensive insights into the binding mode of ANKRD22 and fostamatinib. ANKRD22 exhibited strong binding affinity (ΔG = -7.0 kcal/mol in molecular docking and ∆G_bind = -38.66 ± 6.09 kcal/mol in MDs). Taken together, ANKRD22 could be a promising theragnostic target that might be inhibited by fostamatinib, thereby suppressing PC growth.</p>","PeriodicalId":14031,"journal":{"name":"International Journal of Medical Sciences","volume":"22 8","pages":"1885-1904"},"PeriodicalIF":3.2,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11983316/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143993378","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}