{"title":"Isolation, identification, and challenges of extracellular vesicles: emerging players in clinical applications.","authors":"Xiaoxiao Ma, Lanwei Peng, Xiaohui Zhu, Tianqi Chu, Changcheng Yang, Bohao Zhou, Xiangwei Sun, Tianya Gao, Mengqi Zhang, Ping Chen, Haiyan Chen","doi":"10.1007/s10495-024-02036-2","DOIUrl":"https://doi.org/10.1007/s10495-024-02036-2","url":null,"abstract":"<p><p>Extracellular vesicles (EVs) serve as critical mediators of intercellular communication, encompassing exosomes, microvesicles, and apoptotic vesicles that play significant roles in diverse physiological and pathological contexts. Numerous studies have demonstrated that EVs derived from mesenchymal stem cells (MSC-EVs) play a pivotal role in facilitating tissue and organ repair, alleviating inflammation and apoptosis, enhancing the proliferation of endogenous stem cells within tissues and organs, and modulating immune function-these functions have been extensively utilized in clinical applications. The precise classification, isolation, and identification of MSC-EVs are essential for their clinical applications. This article provides a comprehensive overview of the biological properties of EVs, emphasizing both their advantages and limitations in isolation and identification methodologies. Additionally, we summarize the protein markers associated with MSC-EVs, emphasizing their significance in the treatment of various diseases. Finally, this article addresses the current challenges and dilemmas in developing clinical applications for MSC-EVs, aiming to offer valuable insights for future research.</p>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2024-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142613632","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Lenvatinib inhibits cholangiocarcinoma progression by targeting the FGF19/PI3K/AKT signaling pathway.","authors":"Yingcheng Wei, Lei Yang, Chenwei Tang, Hongkai Zhuang, Xinming Chen, Xiaowu Ma, Xuesong Deng, Yajin Chen, Wenliang Tan, Changzhen Shang","doi":"10.1007/s10495-024-02028-2","DOIUrl":"https://doi.org/10.1007/s10495-024-02028-2","url":null,"abstract":"<p><p>Cholangiocarcinoma (CCA) is known for its high aggressiveness and dismal prognosis, whose effectiveness of systemic therapy remains limited. As a multi-target drug, lenvatinib has exhibited promising effects in many solid tumors. However, the therapeutic role of lenvatinib in CCA is rarely investigated. Here, the in vitro assays including EdU, colony formation, transwell, wound healing, and apoptosis analyses demonstrated that lenvatinib significantly inhibited the proliferation, migration, and invasion, while simultaneously inducing apoptosis of CCA cells. Mechanistically, lenvatinib downregulated the expression of FGF19 and inactivated the PI3K/AKT signaling pathway. Depletion of FGF19 enhanced the anti-tumor effects of lenvatinib, which was attributed to the inhibition of p-PI3K and p-AKT expression in CCA cells. In contrast, overexpression of FGF19 activated the PI3K/AKT signaling pathway, thereby impairing the inhibitory effects of lenvatinib against CCA. In addition, the AKT inhibitor, MK-2206, reinforced the lenvatinib-induced CCA inhibition. Notably, the in vivo experiment confirmed that the subcutaneous tumorigenicity of CCA cells in nude mice was weakened by lenvatinib. Lenvatinib markedly downregulated the expression of FGF19, p-AKT, Ki-67, vimentin, and VEGF in the xenograft tumor tissues. Collectively, these findings demonstrated that lenvatinib inhibits CCA progression by targeting the FGF19/PI3K/AKT signaling pathway. The present study provides novel experimental evidence for the potential clinical application of lenvatinib in CCA, which also highlights the promising role of targeting FGF19 in combined therapeutic approaches for CCA.</p>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2024-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142613633","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ApoptosisPub Date : 2023-09-15DOI: 10.1007/s10495-023-01880-y
Wenjun Zhu, Ziqi Chen, Min Fu, Qianxia Li, Xin Chen, Xiaoyu Li, Na Luo, Wenhua Tang, Feng Yang, Yiling Zhang, Yuanyuan Zhang, Xiaohong Peng, Guangyuan Hu
{"title":"Cuprotosis clusters predict prognosis and immunotherapy response in low-grade glioma","authors":"Wenjun Zhu, Ziqi Chen, Min Fu, Qianxia Li, Xin Chen, Xiaoyu Li, Na Luo, Wenhua Tang, Feng Yang, Yiling Zhang, Yuanyuan Zhang, Xiaohong Peng, Guangyuan Hu","doi":"10.1007/s10495-023-01880-y","DOIUrl":"10.1007/s10495-023-01880-y","url":null,"abstract":"<div><p>Cuprotosis, an emerging mode of cell death, has recently caught the attention of researchers worldwide. However, its impact on low-grade glioma (LGG) patients has not been fully explored. To gain a deeper insight into the relationship between cuprotosis and LGG patients’ prognosis, we conducted this study in which LGG patients were divided into two clusters based on the expression of 18 cuprotosis-related genes. We found that LGG patients in cluster A had better prognosis than those in cluster B. The two clusters also differed in terms of immune cell infiltration and biological functions. Moreover, we identified differentially expressed genes (DEGs) between the two clusters and developed a cuprotosis-related prognostic signature through the least absolute shrinkage and selection operator (LASSO) analysis in the TCGA training cohort. This signature divided LGG patients into high- and low-risk groups, with the high-risk group having significantly shorter overall survival (OS) time than the low-risk group. Its predictive reliability for prognosis in LGG patients was confirmed by the TCGA internal validation cohort, CGGA325 cohort and CGGA693 cohort. Additionally, a nomogram was used to predict the 1-, 3-, and 5-year OS rates of each patient. The analysis of immune checkpoints and tumor mutation burden (TMB) has revealed that individuals belonging to high-risk groups have a greater chance of benefiting from immunotherapy. Functional experiments confirmed that interfering with the signature gene TNFRSF11B inhibited LGG cell proliferation and migration. Overall, this study shed light on the importance of cuprotosis in LGG patient prognosis. The cuprotosis-related prognostic signature is a reliable predictor for patient outcomes and immunotherapeutic response and can help to develop new therapies for LGG.</p></div>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":"29 1-2","pages":"169 - 190"},"PeriodicalIF":6.1,"publicationDate":"2023-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10830610/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10592231","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ApoptosisPub Date : 2023-09-14DOI: 10.1007/s10495-023-01888-4
Ganghao Yang, Yang Yang, Yiping Liu, Xiaoshu Liu
{"title":"Regulation of alveolar macrophage death in pulmonary fibrosis: a review","authors":"Ganghao Yang, Yang Yang, Yiping Liu, Xiaoshu Liu","doi":"10.1007/s10495-023-01888-4","DOIUrl":"10.1007/s10495-023-01888-4","url":null,"abstract":"<div><p>Pulmonary fibrosis (PF) is a disease in which excessive extracellular matrix (ECM) accumulation occurs in pulmonary mesenchyme, which induces the destruction of alveolar structures and poor prognosis. Macrophage death is responsible for ECM accumulation after alveolar epithelial injury in PF. Depending on the local micro-environments, macrophages can be polarized to either classically activated (M1) or alternatively activated (M2) macrophage phenotypes. In general, M1 macrophages can promote inflammation and sterilization, stop the continuous damage process and prevent excessive repair, while M2 macrophages are anti-inflammatory and promote tissue repair, and excessive M2 macrophage activity may inhibit the absorption and degradation of ECM. Emerging evidence has revealed that death forms such as pyroptosis mediated by inflammasome affect polarization direction and ultimately lead to the development of PF. Pharmacological manipulation of macrophages death signals may serve as a logical therapeutic strategy for PF. This review will focus on the current state of knowledge regarding the regulation and underlying mechanisms of macrophages and their mediators in the influence of macrophage death on the development of PF. We expect to provide help in developing effective therapeutic strategies in clinical settings.</p></div>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":"28 11-12","pages":"1505 - 1519"},"PeriodicalIF":7.2,"publicationDate":"2023-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10599212","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ApoptosisPub Date : 2023-09-13DOI: 10.1007/s10495-023-01886-6
Hong-Rui Zhang, Ya-Ping Li, Zi-Jian Shi, Qi-Qi Liang, Si-Yuan Chen, Yi-Ping You, Tao Yuan, Rong Xu, Li-Hui Xu, Dong-Yun Ouyang, Qing-Bing Zha, Xian-Hui He
{"title":"Triptolide induces PANoptosis in macrophages and causes organ injury in mice","authors":"Hong-Rui Zhang, Ya-Ping Li, Zi-Jian Shi, Qi-Qi Liang, Si-Yuan Chen, Yi-Ping You, Tao Yuan, Rong Xu, Li-Hui Xu, Dong-Yun Ouyang, Qing-Bing Zha, Xian-Hui He","doi":"10.1007/s10495-023-01886-6","DOIUrl":"10.1007/s10495-023-01886-6","url":null,"abstract":"<div><p>Macrophages represent the first lines of innate defense against pathogenic infections and are poised to undergo multiple forms of regulated cell death (RCD) upon infections or toxic stimuli, leading to multiple organ injury. Triptolide, an active compound isolated from <i>Tripterygium wilfordii</i> Hook F., possesses various pharmacological activities including anti-tumor and anti-inflammatory effects, but its applications have been hampered by toxic adverse effects. It remains unknown whether and how triptolide induces different forms of RCD in macrophages. In this study, we showed that triptolide exhibited significant cytotoxicity on cultured macrophages in vitro, which was associated with multiple forms of lytic cell death that could not be fully suppressed by any one specific inhibitor for a single form of RCD. Consistently, triptolide induced the simultaneous activation of pyroptotic, apoptotic and necroptotic hallmarks, which was accompanied by the co-localization of ASC specks respectively with RIPK3 or caspase-8 as well as their interaction with each other, indicating the formation of PANoptosome and thus the induction of PANoptosis. Triptolide-induced PANoptosis was associated with mitochondrial dysfunction and ROS production. PANoptosis was also induced by triptolide in mouse peritoneal macrophages in vivo. Furthermore, triptolide caused kidney and liver injury, which was associated with systemic inflammatory responses and the activation of hallmarks for PANoptosis in vivo. Collectively, our data reveal that triptolide induces PANoptosis in macrophages in vitro and exhibits nephrotoxicity and hepatotoxicity associated with induction of PANoptosis in vivo, suggesting a new avenue to alleviate triptolide’s toxicity by harnessing PANoptosis.</p></div>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":"28 11-12","pages":"1646 - 1665"},"PeriodicalIF":7.2,"publicationDate":"2023-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10279211","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ApoptosisPub Date : 2023-09-12DOI: 10.1007/s10495-023-01885-7
Yibing Wang, Peng Jin, Xia Wang
{"title":"N6-methyladenosine regulator YTHDF1 represses the CD8 + T cell-mediated antitumor immunity and ferroptosis in prostate cancer via m6A/PD-L1 manner","authors":"Yibing Wang, Peng Jin, Xia Wang","doi":"10.1007/s10495-023-01885-7","DOIUrl":"10.1007/s10495-023-01885-7","url":null,"abstract":"<div><p>Increasing data and literature have illustrated that tumor immune escape represents a major source of tumor formation and recrudesce. Besides, novel findings also indicate that RNA N<sup>6</sup>-methyladenosine (m<sup>6</sup>A) participates in the human cancer immune escape. Here, our study investigated the functions of m<sup>6</sup>A reader YTHDF1 in prostate cancer (PCa) immune response and explored the functional mechanism. Results reported that YTHDF1 up-regulated in PCa samples and was closely correlated to poor clinical prognosis. Functionally, YTHDF1 inhibited the killing activity of CD8 + T cells to PCa cells, and moreover mitigated the ferroptosis. Mechanistically, PD-L1 acted as the target of YTHDF1, and YTHDF1 upregulated the transcriptional activity of PD-L1 mRNA. Collectively, YTHDF1 promoted functional PD-L1 partially through enhancing its transcriptional stability, which was necessary for PCa cells to evade effector T cell cytotoxicity and CD8 + T cells mediated ferroptosis. In conclusion, these findings indicate that YTHDF1 represses the CD8 + T cell-mediated antitumor immunity and ferroptosis in PCa via m<sup>6</sup>A-PD-L1 manner, which may provide novel insight for PCa immunotherapy.</p></div>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":"29 1-2","pages":"142 - 153"},"PeriodicalIF":6.1,"publicationDate":"2023-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10268845","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Oncogenic and immunological roles of RACGAP1 in pan-cancer and its potential value in nasopharyngeal carcinoma","authors":"Cheng-shan Zheng, Wei-mei Huang, Hong-mei Xia, Jing-lin Mi, Yuan-qing Li, Hui-qing Liang, Li Zhou, Zhou-xue Lu, Fang Wu","doi":"10.1007/s10495-023-01884-8","DOIUrl":"10.1007/s10495-023-01884-8","url":null,"abstract":"<div><p>A particular GTPase-activating protein called RACGAP1 is involved in apoptosis, proliferation, invasion, metastasis, and drug resistance in a variety of malignancies. Nevertheless, the role of RACGAP1 in pan-cancer was less studied, and its value of the expression and prognostic of nasopharyngeal carcinoma (NPC) has not been explored. Hence, the goal of this study was to investigate the oncogenic and immunological roles of RACGAP1 in various cancers and its potential value in NPC. We comprehensively analyzed RACGAP1 expression, prognostic value, function, methylation levels, relationship with immune cells, immune infiltration, and immunotherapy response in pan-cancer utilizing multiple databases. The results discovered that RACGAP1 expression was elevated in most cancers and suggested poor prognosis, which could be related to the involvement of RACGAP1 in various cancer-related pathways such as the cell cycle and correlated with RACGAP1 methylation levels, immune cell infiltration and reaction to immunotherapy, and chemoresistance. RACGAP1 could inhibit anti-tumor immunity and immunotherapy responses by fostering immune cell infiltration and cytotoxic T lymphocyte dysfunction. Significantly, we validated that RACGAP1 mRNA and protein were highly expressed in NPC. The Gene Expression Omnibus database revealed that elevated RACGAP1 expression was associated with shorter PFS in patients with NPC, and RACGAP1 potentially influenced cell cycle progression, DNA replication, metabolism, and immune-related pathways, resulting in the recurrence and metastasis of NPC. This study indicated that RACGAP1 could be a potential biomarker in pan-cancer and NPC.</p></div>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":"29 1-2","pages":"243 - 266"},"PeriodicalIF":6.1,"publicationDate":"2023-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10161202","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"SARS-CoV-2 envelope protein induces necroptosis and mediates inflammatory response in lung and colon cells through receptor interacting protein kinase 1","authors":"Budhadev Baral, Vaishali Saini, Akrati Tandon, Siddharth Singh, Samiksha Rele, Amit Kumar Dixit, Hamendra Singh Parmar, Ajay Kumar Meena, Hem Chandra Jha","doi":"10.1007/s10495-023-01883-9","DOIUrl":"10.1007/s10495-023-01883-9","url":null,"abstract":"<div><p>SARS-CoV-2 Envelope protein (E) is one of the crucial components in virus assembly and pathogenesis. The current study investigated its role in the SARS-CoV-2-mediated cell death and inflammation in lung and gastrointestinal epithelium and its effect on the gastrointestinal-lung axis. We observed that transfection of E protein increases the lysosomal pH and induces inflammation in the cell. The study utilizing Ethidium bromide/Acridine orange and Hoechst/Propidium iodide staining demonstrated necrotic cell death in E protein transfected cells. Our study revealed the role of the necroptotic marker RIPK1 in cell death. Additionally, inhibition of RIPK1 by its specific inhibitor Nec-1s exhibits recovery from cell death and inflammation manifested by reduced phosphorylation of NFκB. The E-transfected cells’ conditioned media induced inflammation with differential expression of inflammatory markers compared to direct transfection in the gastrointestinal-lung axis. In conclusion, SARS-CoV-2 E mediates inflammation and necroptosis through RIPK1, and the E-expressing cells’ secretion can modulate the gastrointestinal-lung axis. Based on the data of the present study, we believe that during severe COVID-19, necroptosis is an alternate mechanism of cell death besides ferroptosis, especially when the disease is not associated with drastic increase in serum ferritin.</p></div>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":"28 11-12","pages":"1596 - 1617"},"PeriodicalIF":7.2,"publicationDate":"2023-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10144964","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ApoptosisPub Date : 2023-08-27DOI: 10.1007/s10495-023-01882-w
Ping Zhang, Chaoting Zhou, Qiangan Jing, Yan Gao, Lei Yang, Yanchun Li, Jing Du, Xiangmin Tong, Ying Wang
{"title":"Role of APR3 in cancer: apoptosis, autophagy, oxidative stress, and cancer therapy","authors":"Ping Zhang, Chaoting Zhou, Qiangan Jing, Yan Gao, Lei Yang, Yanchun Li, Jing Du, Xiangmin Tong, Ying Wang","doi":"10.1007/s10495-023-01882-w","DOIUrl":"10.1007/s10495-023-01882-w","url":null,"abstract":"<div><p><i>APR3</i> (<i>Apoptosis-related protein 3</i>) is a gene that has recently been identified to be associated with apoptosis. The gene is located on human chromosome 2p22.3 and contains both transmembrane and EGF (epidermal growth factor)-like domains. Additionally, it has structural sites, including <i>AP1</i>, <i>SP1</i>, and <i>MEF2D</i>, that indicate <i>NFAT</i> (<i>nuclear factor of activated T cells</i>) and <i>NF-κB</i> (<i>nuclear factor kappa-B</i>) may be transcription factors for this gene. Functionally, APR3 participates in apoptosis due to the induction of mitochondrial damage to release mitochondrial cytochrome C. Concurrently, APR3 affects the cell cycle by altering the expression of Cyclin D1, which, in turn, affects the incidence and growth of malignancies and promotes cell differentiation. Previous reports indicate that APR3 is located in lysosomal membranes, where it contributes to lysosomal activity and participates in autophagy. While further research is required to determine the precise role and molecular mechanisms of APR3, earlier studies have laid the groundwork for APR3 research. There is growing evidence supporting the significance of APR3 in oncology. Therefore, this review aims to examine the current state of knowledge on the role of the newly discovered APR3 in tumorigenesis and to generate fresh insights and suggestions for future research.</p></div>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":"28 11-12","pages":"1520 - 1533"},"PeriodicalIF":7.2,"publicationDate":"2023-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10081294","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"An immunogenic cell death-related signature predicts prognosis and immunotherapy response in stomach adenocarcinoma","authors":"Zitao Liu, Liang Sun, Xingyu Peng, Sicheng Liu, Zhengming Zhu, Chao Huang","doi":"10.1007/s10495-023-01879-5","DOIUrl":"10.1007/s10495-023-01879-5","url":null,"abstract":"<div><p>The immunogenic cell death (ICD) is a specific type of regulatory cell death (RCD), which induces adaptive immunity against antigens of dead cells. ICDs have received increasing attention for their potential role in tumor microenvironment reprogramming and immunotherapy. However, the relationship between ICD-related features and stomach adenocarcinoma (STAD) prognosis, immune cell infiltration and immunotherapy remains unclear. Patients were divided into different ICD-related subtypes by consensus clustering. The differences in prognosis, Tumor microenvironment (TME), and immune checkpoint expression between different ICD-related subtypes were systematically assessed. Additionally, we constructed an ICD-related gene risk score (ICDRS). We systematically analyzed the correlation between ICDRS and prognosis, TME, immunotherapy response and drug sensitivity of gastric cancer. In addition, we explored the role of TGM2 in promoting gastric cancer progression through in vitro experiments. We identified three ICD-associated subtypes by consensus clustering. The ICD gene was highly expressed in Cluster B. Compared with the other two subtypes, Cluster B had better prognosis, higher immune response signaling activity, massive immune cell infiltration and lower tumor purity. Immune checkpoint (ICP) and human leukocyte antigen (HLA) related genes were also highly expressed in Cluster B. In addition, we found that ICDRS is an effective indicator for predicting the prognosis and immune efficacy of STAD. The low ICDRS group has the characteristics of good prognosis, high tumor mutation burden (TMB), high microsatellite instability (MSI), and sensitivity to immunotherapy, while the high ICDRS group is prone to immune escape and immunotherapy resistance. In addition, we found that down-regulating TGM2 gene can inhibit the proliferation and migration of gastric cancer cells through in vitro experiments. Our study found that the model based on ICD features is helpful to clarify the TME characteristics of STAD, and has important clinical significance for evaluating the prognosis and immunotherapy response of STAD patients. TGM2 plays an important role in the progression of STAD, suggesting that TGM2 can be used as a new target for the treatment of STAD.</p></div>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":"28 11-12","pages":"1564 - 1583"},"PeriodicalIF":7.2,"publicationDate":"2023-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10000275","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}