{"title":"CD74 is a potential biomarker predicting the response to immune checkpoint blockade.","authors":"Wen-Qi Shi, Dan-Xun Chen, Ze-Sen Du, Chun-Peng Liu, Tian-Tian Zhai, Feng Pan, Hai-Lu Chen, Wei-Nan Liao, Shao-Hong Wang, Jun-Hui Fu, Si-Qi Qiu, Zhi-Yong Wu","doi":"10.1186/s12935-024-03524-w","DOIUrl":"https://doi.org/10.1186/s12935-024-03524-w","url":null,"abstract":"<p><strong>Background: </strong>Immune checkpoint blockade (ICB) has been improving the patient outcome in multiple cancer types. However, not all patients respond to ICB. Biomarkers are needed for selecting appropriate patients to receive ICB. CD74 is an important chaperone that regulates antigen presentation for immune response. However, the relationship between CD74 expression and ICB response remains elusive.</p><p><strong>Methods: </strong>The unified normalized pan-cancer dataset was downloaded from the UCSC database. Wilcoxon Rank Sum Rank Tests were used to analyze the expression differences between normal and tumor samples in each tumor type. Then, the prognostic value of CD74 was determined using univariable Cox proportional hazards regression analysis. The STRING database was utilized to construct the protein-protein interaction (PPI) network of CD74 and the signal pathways were analyzed as well. The correlation of CD74 expression with immune cells and immune regulating genes was investigated in the TIMER database. The TIDE framework was utilized to evaluate the relationship between CD74 expression and the response to immunotherapy. Moreover, the localization of CD74 in the tumor immune microenvironment was verified using multiplex immunohistochemistry. Clinically annotated samples from 38 patients with esophageal cancer treated with neoadjuvant chemotherapy combined with ICB were analyzed for CD74 expression using immunohistochemistry.</p><p><strong>Results: </strong>In this study, we investigated the prognostic and predictive value of CD74 in different types of cancer. Compared with normal tissue, the expression of CD74 was higher in tumor tissue in various cancers. High expression of CD74 was associated with improved patient prognosis in the majority of cancers. CD74 and its interacting proteins were mainly enriched in the immune-related pathways. The expression of CD74 was significantly positively correlated with B cells, CD4 T-cells, CD8 T-cells, neutrophils, macrophages and dendritic cells. TIDE analysis showed that tumors with high CD74 expression may have better responses to immunotherapy and improved patient survival. In patients with esophageal cancer who had received ICB, higher intratumoral CD74 expression was associated with improved response to ICB.</p><p><strong>Conclusions: </strong>The findings of this study suggest that the high expression of CD74 may be a potential predictive biomarker of response to ICB.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"24 1","pages":"340"},"PeriodicalIF":5.3,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11476377/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142458631","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yang Zhou, Zhenzhen Luo, Jinfeng Guo, Lixia Wu, Xiaoli Zhou, Jun Jie Huang, Daijia Huang, Li Xiao, Qiuhua Duan, Jianhua Chang, Libao Gong, Junjie Hang
{"title":"Pan-cancer analysis of Sp1 with a focus on immunomodulatory roles in gastric cancer.","authors":"Yang Zhou, Zhenzhen Luo, Jinfeng Guo, Lixia Wu, Xiaoli Zhou, Jun Jie Huang, Daijia Huang, Li Xiao, Qiuhua Duan, Jianhua Chang, Libao Gong, Junjie Hang","doi":"10.1186/s12935-024-03521-z","DOIUrl":"https://doi.org/10.1186/s12935-024-03521-z","url":null,"abstract":"<p><strong>Background: </strong>Sp1, a transcription factor, regulates essential cellular processes and plays important tumorigenic roles across diverse cancers. However, comprehensive pan-cancer analyses of its expression and potential immunomodulatory roles remain unexplored.</p><p><strong>Methods: </strong>Utilizing bioinformatics tools and public datasets, we examined the expression of Sp1 across normal tissues, tumors, and immune cells, and screened for pre- and post-transcriptional modifications, including genetic alterations, DNA methylation, and protein phosphorylation, affecting its expression or function. The association of Sp1 expression with immune cell infiltration, tumor mutational burden, and immune checkpoint signaling was also investigated. Single-cell transcriptome data was used to assess Sp1 expression in immune cells in gastric cancer (GC), and findings were corroborated using immunohistochemistry and multiplex immunofluorescence in an immunotherapy-treated patient cohort. The prognostic value of Sp1 in GC patients receiving immunotherapy was evaluated with Cox regression models.</p><p><strong>Results: </strong>Elevated Sp1 levels were observed in various cancers compared to normal tissues, with notable prominence in GC. High Sp1 expression correlated with advanced stage, poor prognosis, elevated tumor mutational burden (TMB), and microsatellite instability (MSI) status, particularly in GC. Significant correlations between Sp1 levels and CD8+ T cell and the M1 phenotype of tumor-associated macrophages were further detected upon multiplex immunofluorescence in GC samples. Interestingly, we verified that GC patients with higher Sp1 levels exhibited improved response to immunotherapy. Moreover, Sp1 emerged as a prognostic and predictive biomarker for GC patients undergoing immunotherapy.</p><p><strong>Conclusions: </strong>Our pan-cancer analysis sheds light on the multifaceted role of Sp1 in tumorigenesis and underscores its potential as a prognostic and predictive biomarker for patients with GC undergoing immunotherapy.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"24 1","pages":"338"},"PeriodicalIF":5.3,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11476248/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142458558","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"RhoA-ROCK2 signaling possesses complex pathophysiological functions in cancer progression and shows promising therapeutic potential.","authors":"Yidi Ning, Minying Zheng, Yue Zhang, Yuqi Jiao, Jiangping Wang, Shiwu Zhang","doi":"10.1186/s12935-024-03519-7","DOIUrl":"https://doi.org/10.1186/s12935-024-03519-7","url":null,"abstract":"<p><p>The Rho GTPase signaling pathway is responsible for cell-specific processes, including actin cytoskeleton organization, cell motility, cell division, and the transcription of specific genes. The implications of RhoA and the downstream effector ROCK2 in cancer epithelial-mesenchymal transition, migration, invasion, and therapy resistance associated with stem cells highlight the potential of targeting RhoA/ROCK2 signaling in therapy. Tumor relapse can occur due to cancer cells that do not fully respond to adjuvant chemoradiotherapy, targeted therapy, or immunotherapy. Rho signaling-mediated mitotic defects and cytokinesis failure lead to asymmetric cell division, allowing cells to form polyploids to escape cytotoxicity and promote tumor recurrence and metastasis. In this review, we elucidate the significance of RhoA/ROCK2 in the mechanisms of cancer progression and summarize their inhibitors that may improve treatment strategies.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"24 1","pages":"339"},"PeriodicalIF":5.3,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11475559/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142458560","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xi Wang, Hengyuan Gao, Wenjun Pu, Zhipeng Zeng, Nan Xu, Xunpeng Luo, Donge Tang, Yong Dai
{"title":"Dysregulation of pseudouridylation in small RNAs contributes to papillary thyroid carcinoma metastasis.","authors":"Xi Wang, Hengyuan Gao, Wenjun Pu, Zhipeng Zeng, Nan Xu, Xunpeng Luo, Donge Tang, Yong Dai","doi":"10.1186/s12935-024-03482-3","DOIUrl":"https://doi.org/10.1186/s12935-024-03482-3","url":null,"abstract":"<p><strong>Background: </strong>Previous studies have indicated that ψ-modified small RNAs play crucial roles in tumor metastasis. However, the ψ-modified small RNAs during metastasis of PTC are still unclear.</p><p><strong>Methods: </strong>We compared the pseudouridine synthase 7 (PUS7) alteration between metastatic and non-metastatic PTCs, and investigated its correlation with clinicopathological features. Additionally, we employed a small RNA ψ modification microarray to examine the small RNA ψ modification profile in both metastatic and non-metastatic PTCs, as well as paired paracancerous tissues. The key molecule involved in ψ modification, pre-miR-8082, was identified and found to regulate the expression of CD47. Experiments in vitro were conducted to further investigate the function of PUS7 and CD47 in PTC.</p><p><strong>Results: </strong>Our results demonstrated that PUS7 was down-regulated in PTC and was closely associated with metastasis. Moreover, the ψ modification of pre-miR-8082 was found to be decreased, resulting in down-expression of pre-miR-8082 and miR-8082, leading to the loss of the inhibitory effect on CD47, thereby promoting tumor migration.</p><p><strong>Conclusions: </strong>Our study demonstrates that PUS7 promotes the inhibition of CD47 and inhibits metastasis of PTC cells by regulating the ψ modification of pre-miR-8082. These results suggest that PUS7 and ψ pre-miR-8082 may serve as potential targets and diagnostic markers for PTC metastasis.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"24 1","pages":"337"},"PeriodicalIF":5.3,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11476189/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142458557","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Serum exosomal small nucleolar RNA (snoRNA) signatures as a predictive biomarker for benign and malignant pulmonary nodules.","authors":"Fei Cao, Qian You, Feng Zhu, Yu Zhang","doi":"10.1186/s12935-024-03522-y","DOIUrl":"https://doi.org/10.1186/s12935-024-03522-y","url":null,"abstract":"<p><p>Low-dose CT (LDCT) is increasingly recognized as the preferred method for detecting pulmonary nodules. However, distinguishing whether a nodule is benign or malignant often necessitates repeated scans or invasive tissue sampling procedures. Therefore, there is a pressing need for non-invasive techniques to minimize unnecessary interventions. This study aim to investigate the expression profile of exosomal snoRNA in the serum of patients with benign and malignant pulmonary nodules. We identified a total of 278 snoRNAs in serum exosomes, revealing significant differences in snoRNA levels between patients with malignant and benign nodules. Specifically, the upregulated snoRNAs U78 and U37 were validated through qRT-PCR and were found significantly elevated in the serum of patients with malignant pulmonary nodules, positioning them as promising biomarkers for the early detection of lung cancer. This study underscores the potential of serum exosomal U78 and U37 as critical tools for assessing the risk of pulmonary nodules identified through CT screening.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"24 1","pages":"341"},"PeriodicalIF":5.3,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11475846/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142458561","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yu Chen, Shen Chen, Zhenkai Wu, Quan Cheng, Dan Ji
{"title":"Hypoxia-related lncRNA correlates with prognosis and immune microenvironment in uveal melanoma.","authors":"Yu Chen, Shen Chen, Zhenkai Wu, Quan Cheng, Dan Ji","doi":"10.1186/s12935-024-03509-9","DOIUrl":"10.1186/s12935-024-03509-9","url":null,"abstract":"<p><strong>Background: </strong>Hypoxia-related genes are linked to the prognosis of various solid malignant tumors. However, the role of hypoxia-related long non-coding RNAs (HRLs) in uveal melanoma (UVM) remains unclear. This study aimed to identify HRLs associated with UVM prognosis and develop a novel risk signature to predict patient outcomes.</p><p><strong>Methods: </strong>Data from 80 UVM samples were obtained from The Cancer Genome Atlas. Prognostic HRLs were screened using Cox univariate and Pearson correlation analyses. HRL signature were constructed using Lasso analysis, and gene enrichment analysis was performed to explore the association between HRLs and immune features. Cell Counting Kit-8 assay was used to measure the propagation of human uveal melanoma (MuM2B) cells, while tumor invasion and migration were evaluated using Transwell and wound-healing experiments. Inflammatory factors and macrophage polarization were evaluated using quantitative PCR.</p><p><strong>Results: </strong>In total, 621 prognostic HRLs were screened and constructed in 12 HRLs. The risk score showed a significant correlation with the survival time of patients with UVM. Additionally, HRL correlated with diverse key immune checkpoints, revealing possible targets for immunotherapy. Immune-related pathways were highly enriched in the high-risk group. LINC02367, a protective HRL, was associated with the tumor microenvironment and survival time of patients with UVM. In vitro, LINC02367 significantly influenced MuM2B proliferation and migration. It also modulated macrophage polarization by regulating inflammatory factor levels, thereby affecting the immune microenvironment.</p><p><strong>Conclusions: </strong>We developed a novel HRL signature to predict prognosis in patients with UVM. HRLs are potential biomarkers and therapeutic targets for the treatment of UVM.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"24 1","pages":"336"},"PeriodicalIF":5.3,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11465649/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142388260","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The axis of tumor-associated macrophages, extracellular matrix proteins, and cancer-associated fibroblasts in oncogenesis.","authors":"Shuhong Yu, Siyu Wang, Xuanyu Wang, Ximing Xu","doi":"10.1186/s12935-024-03518-8","DOIUrl":"https://doi.org/10.1186/s12935-024-03518-8","url":null,"abstract":"<p><p>The extracellular matrix (ECM) is a complex, dynamic network of multiple macromolecules that serve as a crucial structural and physical scaffold for neighboring cells. In the tumor microenvironment (TME), ECM proteins play a significant role in mediating cellular communication between cancer-associated fibroblasts (CAFs) and tumor-associated macrophages (TAMs). Revealing the ECM modification of the TME necessitates the intricate signaling cascades that transpire among diverse cell populations and ECM proteins. The advent of single-cell sequencing has enabled the identification and refinement of specific cellular subpopulations, which has substantially enhanced our comprehension of the intricate milieu and given us a high-resolution perspective on the diversity of ECM proteins. However, it is essential to integrate single-cell data and establish a coherent framework. In this regard, we present a comprehensive review of the relationships among ECM, TAMs, and CAFs. This encompasses insights into the ECM proteins released by TAMs and CAFs, signaling integration in the TAM-ECM-CAF axis, and the potential applications and limitations of targeted therapies for CAFs. This review serves as a reliable resource for focused therapeutic strategies while highlighting the crucial role of ECM proteins as intermediates in the TME.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"24 1","pages":"335"},"PeriodicalIF":5.3,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11459962/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142388261","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Arefeh Zabeti Touchaei, Seyedeh Elham Norollahi, Ali Najafizadeh, Kosar Babaei, Elahe Bakhshalipour, Sogand Vahidi, Ali Akbar Samadani
{"title":"Therapeutic combinations of exosomes alongside cancer stem cells (CSCs) and of CSC-derived exosomes (CSCEXs) in cancer therapy.","authors":"Arefeh Zabeti Touchaei, Seyedeh Elham Norollahi, Ali Najafizadeh, Kosar Babaei, Elahe Bakhshalipour, Sogand Vahidi, Ali Akbar Samadani","doi":"10.1186/s12935-024-03514-y","DOIUrl":"10.1186/s12935-024-03514-y","url":null,"abstract":"<p><p>Exosomes which are membrane vesicles released by cells have gained significant interest in the field of cancer therapy as a novel means of intercellular communication. Their role in immune activation and their pathophysiological functions in cancer therapy have been recognized. Exosomes carry diverse bioactive components including proteins, mRNA, microRNAs, and bioactive lipids. These molecules have therapeutic potential in promoting tissue regeneration, supporting stem cell activity, preventing cell death, modulating immune responses, and promoting the growth of new blood vessels. However, the precise roles of exosomes derived from mesenchymal stem cells (MSCs) in the treatment of various cancers are still not fully understood. Consequently, cancer stem cells (CSCs) can self-renew and differentiate into various cell types. Understanding the mechanisms that sustain their persistence is crucial for developing effective therapies. Exosomes have recently gained interest as vehicles for intercellular communication between CSCs and non-CSCs, influencing cancer progression and the microenvironment. Research is ongoing on the utilization of exosomes derived from cancer stem cells (CSC-Exosome) for cancer treatment. The composition of extracellular vesicles is influenced by the specific type and condition of the cells from which they are secreted. Circulating exosomes contain stable RNA molecules such as mRNAs, microRNAs, and long non-coding RNAs (lncRNAs). In this review, we will explore the significance of exosomes and their diverse cellular combinations in the context of cancer therapy.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"24 1","pages":"334"},"PeriodicalIF":5.3,"publicationDate":"2024-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11453077/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142379125","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Non-coding RNAs as potential targets in metformin therapy for cancer.","authors":"Yihan Zhang, Yunhao Wu, Zixu Liu, Kangping Yang, Hui Lin, Kai Xiong","doi":"10.1186/s12935-024-03516-w","DOIUrl":"10.1186/s12935-024-03516-w","url":null,"abstract":"<p><p>Metformin, a widely used oral hypoglycemic drug, has emerged as a potential therapeutic agent for cancer treatment. While initially known for its role in managing diabetes, accumulating evidence suggests that metformin exhibits anticancer properties through various mechanisms. Several cellular or animal experiments have attempted to elucidate the role of non-coding RNA molecules, including microRNAs and long non-coding RNAs, in mediating the anticancer effects of metformin. The present review summarized the current understanding of the mechanisms by which non-coding RNAs modulate the response to metformin in cancer cells. The regulatory roles of non-coding RNAs, particularly miRNAs, in key cellular processes such as cell proliferation, cell death, angiogenesis, metabolism and epigenetics, and how metformin affects these processes are discussed. This review also highlights the role of lncRNAs in cancer types such as lung adenocarcinoma, breast cancer, and renal cancer, and points out the need for further exploration of the mechanisms by which metformin regulates lncRNAs. In addition, the present review explores the potential advantages of metformin-based therapies over direct delivery of ncRNAs, and this review highlights the mechanisms of non-coding RNA regulation when metformin is combined with other therapies. Overall, the present review provides insights into the molecular mechanisms underlying the anticancer effects of metformin mediated by non-coding RNAs, offering novel opportunities for the development of personalized treatment strategies in cancer patients.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"24 1","pages":"333"},"PeriodicalIF":5.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11445969/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142361136","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Comprehensive analysis of bulk, single-cell RNA sequencing, and spatial transcriptomics revealed IER3 for predicting malignant progression and immunotherapy efficacy in glioma.","authors":"Qi Wang, Chunyu Zhang, Ying Pang, Meng Cheng, Rui Wang, Xu Chen, Tongjie Ji, Yuntong Yang, Jing Zhang, Chunlong Zhong","doi":"10.1186/s12935-024-03511-1","DOIUrl":"10.1186/s12935-024-03511-1","url":null,"abstract":"<p><strong>Background: </strong>As part of stress-triggered molecules, immediate early response 3 (IER3) dysregulation has been reported to sustain pro-oncogenic pathways and precede malignant transformation. However, the role of IER3 in glioma pathology is ill-defined.</p><p><strong>Methods: </strong>Immunohistochemistry (IHC) assay and publicly available glioma datasets were used to calculate the IER3 expression level in glioma. Wound healing, invasion and cell counting kit-8 (CCK8) assays were applied to measure the cell viability and capacities of migration and invasion of glioma cells in vitro. The immunofluorescence (IF) assay was used to assess the expression associations of IER3 with CCL2 and TGFBI. Cox regression analysis and Kaplan-Meier (K-M) curve were introduced to compute the prognosis-predicting value of IER3. Variations in copy number (CNVs), single nucleotide (SNVs), and methylation profiles were analyzed to illustrate the epigenetic modifications of IER3. Gliomas were divided into two subgroups using the restricted cubic spline (RCS) method. RESULTS IER3: was overexpressed and hypomethylated in gliomas and significantly associated with the dismal prognosis of glioma samples. Samples in the high IER3 subgroup were characterized by increased infiltration of tumor-associated monocytes/macrophages (TAMMs), as well as the elevated sensitivity to Dabrafenib, an inhibitor of BRAF. In addition, this subgroup demonstrated a low mutation rate of IDH, high gain rates of BRAF, ELTD1, and PDGFA. Gliomas with relatively low IER3 expression demonstrated a less invasive subtype and were featured by favorable prognosis, increased response to immunotherapy, and adjuvant chemotherapy plus radiotherapy. The IF assay revealed that IER3 was co-localized and co-expressed with TGFBI. The glioma cells with small interfering RNA (siRNA)-silenced IER3 displayed lower migration, invasion, proliferation, and cell viability than the control group.</p><p><strong>Conclusions: </strong>In this study, we identified IER3 upregulation as an essential biomarker that could assist in adjuvant therapy and prognosis prediction for gliomas.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"24 1","pages":"332"},"PeriodicalIF":5.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11443732/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142361125","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}