BACKGROUND According to study,anoikis-related genes(ARGs)have been demonstrated to play a significant impact in cirrhosis,a major disease threatening human health worldwide.AIM To investigate the relationship between ARGs and cirrhosis development to provide insights into the clinical treatment of cirrhosis.METHODS RNA-sequencing data related to cirrhosis were obtained from the Gene Expression Omnibus database.Differentially expressed genes(DEGs)between cirrhotic and normal tissues were intersected with ARGs to derive differentially expressed ARGs(DEARGs).The DEARGs were filtered using the least absolute shrinkage and selection operator,support vector machine recursive feature elimination,and random forest algorithms to identify biomarkers for cirrhosis.These biomarkers were used to create a nomogram for predicting the prognosis of cirrhosis.The proportions of diverse immune cell subsets in cirrhotic vs normal tissues were compared using the CIBERSORT computational method.In addition,the linkage between immune cells and biomarkers was assessed,and a regulatory network of mRNA,miRNA,and transcription factors was constructed relying on the biomarkers.RESULTS The comparison of cirrhotic and normal tissue samples led to the identification of 635 DEGs.Subsequent intersection of the DEGs with ARGs produced a set of 26 DEARGs.Subsequently,three DEARGs,namely,ACTG1,STAT1,and CCR7,were identified as biomarkers using three machine-learning algorithms.The proportions of M1 and M2 macrophages,resting CD4 memory T cells,resting mast cells,and plasma cells significantly differed between cirrhotic and normal tissue samples.The proportions of M1 and M2 macrophages,resting CD4 memory T cells,and resting mast cells were significantly correlated with the expression of the three biomarkers.The mRNA–miRNA–TF network showed that ACTG1,CCR7,and STAT1 were regulated by 28,42,and 35 miRNAs,respectively.Moreover,AR,MAX,EP300,and FOXA1 were found to regulate four miRNAs related to the biomarkers.CONCLUSION This study revealed ACTG1,STA
Jiang-Yan LuoSheng ZhengJuan YangChi MaXiao-Ying MaXing-Xing WangXin-Nian FuXiao-Zhou Mao
Objective:Osteosarcoma is a highly aggressive primary malignant bone tumor commonly seen in children and adolescents,with a poor prognosis.Anchorage-dependent cell death(anoikis)has been proven to be indispensable in tumor metastasis,regulating the migration and adhesion of tumor cells at the primary site.However,as a type of programmed cell death,anoikis is rarely studied in osteosarcoma,especially in the tumor immune microenvironment.This study aims to clarify prognostic value of anoikis and tumor immune microenvironment-related gene in the treatment of osteosarcoma.Methods:Anoikis-related genes(ANRGs)were obtained from GeneCards.Clinical information and ANRGs expression profiles of osteosarcoma patients were sourced from the therapeutically applicable research to generate effective therapies and Gene Expression Omnibus(GEO)databases.ANRGs highly associated with tumor immune microenvironment were identified by the estimate package and the weighted gene coexpression network analysis(WGCNA)algorithm.Machine learning algorithms were performed to construct long-term survival predictive strategy,each sample was divided into high-risk and low-risk subgroups,which was further verified in the GEO cohort.Finally,based on single-cell RNA-seq from the GEO database,analysis was done on the function of signature genes in the osteosarcoma tumor microenvironment.Results:A total of 51 hub ANRGs closely associated with the tumor microenvironment were identified,from which 3 genes(MERTK,BNIP3,S100A8)were selected to construct the prognostic model.Significant differences in immune cell activation and immune-related signaling pathways were observed between the high-risk and low-risk groups based on tumor microenvironment analysis(all P<0.05).Additionally,characteristic genes within the osteosarcoma microenvironment were identified in regulation of intercellular crosstalk through the GAS6-MERTK signaling pathway.Conclusion:The prognostic model based on ANRGs and tumor microenvironment demonstrate good predictive power and provide m
Loss of susceptibility to anoikis signals is a crucial step in metastasis.Anoikis resistance therefore represents a promising adjuvant therapeutic target for cancer management.In this study,we have conducted a rationalized screening to search for novel leading anoikis sensitizer from daily foods.Among 19 tested dietary phytochemicals,the best results were obtained with apigenin,a natural component of celery.Phenotypically,apigenin sensitized breast cancer cells to anoikis,lowered the number of circulating tumor cells,and protected against breast cancer metastasis to lung in mice.Mechanistically,we demonstrated that the thromboxane A_(2)(TXA_(2))-TXA_(2)receptor(TP)axis has a critical role in acquired anoikis resistance by activating PI3K-Akt signaling pathway.Blockage of TXA_(2)signaling up-regulated p53 as well as its target gene p21,caused a G1 phase arrest,and finally led to apoptosis in breast cancer cells.TXA_(2)level was positively correlated with breast cancer cell anoikis rate,and apigenin significantly inhibited TXA_(2)biosynthesis in vitro and in vivo.Collectively,we identified apigenin as a potent anoikis sensitizer with anti-metastatic properties in a mouse model of breast cancer,and these findings might provide a rationale for introducing apigenin supplementation to breast cancer patients.
Tumor metastasis,the apex of cancer progression,poses a formidable challenge in therapeutic endeavors.Circulating tumor cells(CTCs),resilient entities originating from primary tumors or their metastases,significantly contribute to this process by demonstrating remarkable adaptability.They survive shear stress,resist anoikis,evade immune surveillance,and thwart chemotherapy.This comprehensive review aims to elucidate the intricate landscape of CTC formation,metastatic mechanisms,and the myriad factors influencing their behavior.Integral signaling pathways,such as integrin-related signaling,cellular autophagy,epithelial-mesenchymal transition,and interactions with platelets,are examined in detail.Furthermore,we explore the realm of precision nanomedicine design,with a specific emphasis on the anoikis‒platelet interface.This innovative approach strategically targets CTC survival mechanisms,offering promising avenues for combatting metastatic cancer with unprecedented precision and efficacy.The review underscores the indispensable role of the rational design of platelet-based nanomedicine in the pursuit of restraining CTC-driven metastasis.
子宫内膜癌(uterine corpus endometrial carcinoma,UCEC)是最常见的女性生殖系统肿瘤,肿瘤发生远端转移的患者预后极差。失巢凋亡(anoikis)是一种特殊的程序性细胞死亡形式,在肿瘤的侵袭和转移中起着关键作用,分析失巢凋亡相关基因与UCEC患者预后之间的关系将为临床治疗提供指导。本研究采用非监督一致性聚类算法对数据集进行分组,分析患者的肿瘤微环境(tumor microenvironment,TME)与临床特征的差异。同时,筛选预后相关的失巢凋亡基因,构建风险评分模型,评估UCEC患者的风险评分与临床特征、TME和药物治疗反应之间的关系。在分析失巢凋亡相关基因表达差异的基础上确定两个明确的聚类(A簇和B簇),与A簇UCEC患者相比,B簇UCEC患者的总生存期较短、免疫浸润水平较低。构建的风险评分模型可量化失巢凋亡相关基因的调控模式,高风险评分组表现为预后不良且免疫细胞浸润水平低,而低风险评分组则相反。药物敏感性分析结果表明,高风险评分的人群可能从靶向有丝分裂和DNA修复通路的药物中获得更佳疗效。本研究揭示了失巢凋亡相关基因与临床特征、TME和药物治疗反应之间的潜在关系,并阐明了其在UCEC治疗中的价值。
