Journal of Immunotherapy最新文献

Integrative Multi-Omics Analysis Reveals Molecular Subtypes of Ovarian Cancer and Constructs Prognostic Models. 综合多组学分析揭示卵巢癌分子亚型并构建预后模型。

IF 3.2 4区医学

Journal of Immunotherapy Pub Date : 2025-07-01 Epub Date: 2025-04-09 DOI: 10.1097/CJI.0000000000000557

Min Zhou, Jie Pi, Yuzi Zhao

{"title":"Integrative Multi-Omics Analysis Reveals Molecular Subtypes of Ovarian Cancer and Constructs Prognostic Models.","authors":"Min Zhou, Jie Pi, Yuzi Zhao","doi":"10.1097/CJI.0000000000000557","DOIUrl":"10.1097/CJI.0000000000000557","url":null,"abstract":"Abstract: Ovarian cancer (OV) remains the most lethal gynecological malignancy. The aim of this study was to identify molecular subtypes of OV through integrative multi-omics analysis and construct machine learning-based prognostic models for predicting the efficacy of immunotherapy. In here, the mutation, copy number variation, RNA sequencing expression profiles, and clinical information were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Multi-omics data were stratified using the MOVICS package, identifying different molecular subtypes. Our analysis identified 2 molecular subtypes (CS1 and CS2) with significant survival differences. Transcriptional regulatory network analysis revealed differential activation of transcription factors such as FOXA1 and GATA3 in CS1, whereas AR and ESR2 were enriched in CS2. A robust prognostic signature comprising 5 key genes was developed through the integration of 10 machine learning algorithms, demonstrating high predictive power across data sets. Immune cell infiltration analysis revealed that anti-tumor immune cells were more abundant in low-risk groups, whereas pro-tumor immune cells predominated in high-risk groups. Furthermore, low-risk patients exhibited better immunotherapy responses and higher tumor mutational burden (TMB). In conclusion, our findings underscore the potential of multi-omics integration in unveiling novel OV subtypes and constructing predictive models that inform personalized treatment strategies. Future research should focus on validating these findings in larger cohorts to enhance OV management through targeted therapeutic approaches.","PeriodicalId":15996,"journal":{"name":"Journal of Immunotherapy","volume":" ","pages":"197-208"},"PeriodicalIF":3.2,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143811550","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Dual Roles of EZH2 in Tumor Proliferation and Immune Evasion in Lung Squamous Cell Carcinoma: A Pathway to Novel Immunotherapeutic Approaches. EZH2在肺鳞状细胞癌的肿瘤增殖和免疫逃避中的双重作用：一种新的免疫治疗途径

IF 3.2 4区医学

Journal of Immunotherapy Pub Date : 2025-07-01 Epub Date: 2025-06-04 DOI: 10.1097/CJI.0000000000000560

Ling Xu, Chun Ye, Shuihong Yu

{"title":"Dual Roles of EZH2 in Tumor Proliferation and Immune Evasion in Lung Squamous Cell Carcinoma: A Pathway to Novel Immunotherapeutic Approaches.","authors":"Ling Xu, Chun Ye, Shuihong Yu","doi":"10.1097/CJI.0000000000000560","DOIUrl":"https://doi.org/10.1097/CJI.0000000000000560","url":null,"abstract":"Abstract: Lung squamous cell carcinoma (LUSC) remains a major clinical challenge due to its aggressive nature and poor prognosis. Enhancer of zeste homolog 2 (EZH2), a key epigenetic regulator within the polycomb repressive complex 2 (PRC2), has emerged as a critical player in cancer progression. This study investigates the dual role of EZH2 in driving tumor proliferation and modulating the immune microenvironment in LUSC. Bioinformatics analysis revealed significant upregulation of EZH2 in LUSC tissues compared with normal counterparts, with high EZH2 expression correlating with improved overall survival in early-stage patients. Functional assays in EZH2 knockout LUSC cell lines demonstrated reduced tumor cell proliferation, migration, and invasion alongside enhanced apoptosis and cell cycle arrest. Furthermore, in vivo studies using an EZH2 knockout mouse model showed decreased tumor growth and increased immune cell infiltration, including CD8+ T cells, macrophages, and neutrophils. These findings highlight the pivotal role of EZH2 in promoting tumor progression and orchestrating immune evasion mechanisms in LUSC. Given its multifaceted influence on tumor biology and the immune landscape, EZH2 represents a promising therapeutic target for improving outcomes in LUSC patients. Future studies should explore the therapeutic potential of targeting EZH2 to enhance immune responses and overcome resistance to current treatments.","PeriodicalId":15996,"journal":{"name":"Journal of Immunotherapy","volume":"48 6","pages":"221-230"},"PeriodicalIF":3.2,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144216047","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Effects of Antibiotics on First-line Immunotherapy in Patients With Recurrent or Metastatic Nasopharyngeal Carcinoma. 抗生素对鼻咽癌复发或转移患者一线免疫治疗的影响。

IF 3.2 4区医学

Journal of Immunotherapy Pub Date : 2025-07-01 Epub Date: 2025-04-10 DOI: 10.1097/CJI.0000000000000556

Yuting Fang, Binhao Wu, Rong Zhang, Xiaozhong Chen, Feng Jiang, Qifeng Jin, Ting Jin, Shuang Huang, Changjuan Tao, Mengyun Qiang, Yongfeng Piao, Yonghong Hua, Xinglai Feng, Caineng Cao

{"title":"Effects of Antibiotics on First-line Immunotherapy in Patients With Recurrent or Metastatic Nasopharyngeal Carcinoma.","authors":"Yuting Fang, Binhao Wu, Rong Zhang, Xiaozhong Chen, Feng Jiang, Qifeng Jin, Ting Jin, Shuang Huang, Changjuan Tao, Mengyun Qiang, Yongfeng Piao, Yonghong Hua, Xinglai Feng, Caineng Cao","doi":"10.1097/CJI.0000000000000556","DOIUrl":"10.1097/CJI.0000000000000556","url":null,"abstract":"Immunotherapy combined with chemotherapy has become the first-line treatment for recurrent or metastatic nasopharyngeal carcinoma (RM-NPC). However, the impact of antibiotic (ATB) use on the efficacy of immunotherapy in RM-NPC remains unclear. A total of 200 patients with RM-NPC who started first-line immunotherapy between October 2021 and September 2023 were included. Forty-six patients received ATB within 60 days before and 42 days after the first infusion of immunotherapy (group ATB+), and the remaining 154 patients were in group ATB-. The median progression-free survival (PFS) times of the ATB+ and ATB- groups were 11.20 and 19.87 months, respectively ( P = 0.061). The 2-year overall survival (OS) rates of the ATB+ and ATB- groups were 52.6% and 76.7%, respectively ( P = 0.001). In multivariate analysis, ATB use was significantly associated with worse OS (hazard ratio = 2.549, P = 0.002). No significant differences were observed between the 2 groups in terms of grade 3+ treatment-related adverse events. ATB use in RM-NPC may reduce the effectiveness of first-line immunotherapy.","PeriodicalId":15996,"journal":{"name":"Journal of Immunotherapy","volume":" ","pages":"231-236"},"PeriodicalIF":3.2,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144011811","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Identification of Immune Characteristics of 2 Subtypes of Breast Cancer by Combining Polyamine Metabolism-related Genes to Help With Immunotherapy. 联合多胺代谢相关基因帮助免疫治疗鉴定2种亚型乳腺癌的免疫特性

IF 3.2 4区医学

Journal of Immunotherapy Pub Date : 2025-07-01 Epub Date: 2025-04-30 DOI: 10.1097/CJI.0000000000000559

Xiuwen Yi, Bin Tang, Qinghua Mo, Yulan Tang, Wei Fu, Lingling Zhang, Liming Xie

{"title":"Identification of Immune Characteristics of 2 Subtypes of Breast Cancer by Combining Polyamine Metabolism-related Genes to Help With Immunotherapy.","authors":"Xiuwen Yi, Bin Tang, Qinghua Mo, Yulan Tang, Wei Fu, Lingling Zhang, Liming Xie","doi":"10.1097/CJI.0000000000000559","DOIUrl":"10.1097/CJI.0000000000000559","url":null,"abstract":"This project aims to explore the clustering value of polyamine metabolism-related genes (PMRGs) in breast cancer (BC) to assist treatment. ConsensusClusterPlus R package was employed to cluster BC patients based on the expression of PMRGs. Using the edgeR R package, we analyzed differentially expressed genes (DEGs) of different molecular clusters. Core genes were screened and enriched by the PPI network. Univariate COX was applied to determine genes tightly linked with survival. ConsensusClusterPlus R package was employed to cluster PMRGs. Differences in immune infiltration and expression of immune checkpoints between 2 subgroups were analyzed. Response to immunotherapy was assessed based on the expression level of immunophenoscore (IPS). Drug sensitivity of different PMRG clusters was assessed by pRRophitic R package. We clustered BC patients into 2 different subtypes with different survival rates and biological functions based on the expression of 16 PMRGs. Application of univariate COX analysis identified genes greatly associated with survival and divided BC patients into 2 different PMRG clusters. Patients in the 2 clusters exhibited differences in overall survival rate and immune cell infiltration levels, with multiple immune cells displaying higher immune levels in PMRG cluster 2. PMRG cluster 2 demonstrated higher expression of HLA and IC as well as IPS. Cluster 1 exhibited higher sensitivity to (5Z)-7-Oxozeaenol, 5-Fluorouracil, and 681640, while cluster 2 exhibited higher sensitivity to A-443654 and A-770041. We identified 2 clusters of PMRG with significant differences in the immune microenvironment in BC and predicted potential drugs, aiming to find new directions for clinical treatment of BC.","PeriodicalId":15996,"journal":{"name":"Journal of Immunotherapy","volume":" ","pages":"209-220"},"PeriodicalIF":3.2,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144004130","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Machine Learning Characterization of Immunometabolism in the Tumor Microenvironment and Immunotherapy Responses in Bladder Cancer. 膀胱癌肿瘤微环境中免疫代谢的机器学习表征和免疫治疗反应。

IF 3.2 4区医学

Journal of Immunotherapy Pub Date : 2025-06-18 DOI: 10.1097/CJI.0000000000000568

Wei Peng, Xiaoshan Li, Shiping Wei, Wei Liu

{"title":"Machine Learning Characterization of Immunometabolism in the Tumor Microenvironment and Immunotherapy Responses in Bladder Cancer.","authors":"Wei Peng, Xiaoshan Li, Shiping Wei, Wei Liu","doi":"10.1097/CJI.0000000000000568","DOIUrl":"https://doi.org/10.1097/CJI.0000000000000568","url":null,"abstract":"Immune dysregulation and metabolism reprogramming are implicated in bladder cancer (BLCA), the relationships between immunometabolism (IMB) and BLCA remain poorly understood. We identified the expression patterns of IMB-related genes and their relationship with prognosis, ultimately developing a machine learning prognostic model. We performed a comprehensive investigation into UCN2 function in BLCA by qPCR, immunohistochemistry, Western blot, Transwell migration assay, and flow cytometry analysis. Two BLCA subclasses were identified, each exhibiting distinctive molecular patterns. Then, an IMB.score was conducted, the IMB.score not only reflected the characteristics of the clinical but also provided insights into immunotherapy efficacy. Specifically, high IMB.score category exhibited a more active TME and unfavorable prognosis; those in the high IMB.score category were more responsive to immunotherapy, suggesting an \"immunity tidal model\" phenotype. Besides, UCN2 is overexpressed in BLCA tissues, and was found to be positively associated with malignant phenotypes and a poorer prognosis for BLCA. Furthermore, by silencing the expression of UCN2, we observed a significant reduction in the proliferation, migration, and invasion of BLCA cells in vitro. UCN2 is considered a crucial gene in IMB that plays a significant role in the onset and development of BLCA.","PeriodicalId":15996,"journal":{"name":"Journal of Immunotherapy","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144325969","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The Efficacy and Safety of TACE or HAIC Combined With ICIs and Angiogenesis Inhibitors in Unresectable Hepatocellular Carcinoma. TACE或HAIC联合ICIs和血管生成抑制剂治疗不可切除肝癌的疗效和安全性。

IF 3.2 4区医学

Journal of Immunotherapy Pub Date : 2025-06-03 DOI: 10.1097/CJI.0000000000000566

Qing Wu, Ping Li, Nan Lin, BinBin Mao, Xianhe Xie

{"title":"The Efficacy and Safety of TACE or HAIC Combined With ICIs and Angiogenesis Inhibitors in Unresectable Hepatocellular Carcinoma.","authors":"Qing Wu, Ping Li, Nan Lin, BinBin Mao, Xianhe Xie","doi":"10.1097/CJI.0000000000000566","DOIUrl":"https://doi.org/10.1097/CJI.0000000000000566","url":null,"abstract":"We aimed to investigate the efficacy and safety of transarterial chemoembolization (TACE) or hepatic arterial infusion chemotherapy (HAIC) combined with immune checkpoint inhibitors (ICIs) and angiogenesis inhibitors in unresectable hepatocellular carcinoma (uHCC). The endpoints were the objective response rate (ORR), disease control rate (DCR), conversion rate, progression-free survival (PFS), overall survival (OS), and the incidence of adverse events (AEs). Stratified analyses were accomplished based on local treatment and evaluation criteria. Totally, 4930 individuals from 76 studies were recruited. For initial uHCC treated with the triple therapy, the pooled pathologic complete response (pCR) rate, major pathologic response (MPR) rate, and conversion resection rate were 29.91%, 44.81%, and 30.98%; the ORR and DCR were 38.52% and 84.42% according to RECIST 1.1, 57.82% and 85.82% by mRECIST 1.1. Furthermore, PFS rates at 6-months, 12-months, 18-months, 24-months, and 30-months were 74.77%, 44.30%, 30.97%, 22.71%, and 15.35%; while OS rates at 6-months, 12-months, 18-months, 24-months, 30-months, and 36-months were 94.94%, 76.95%, 58.17%, 45.19%, 27.38%, and 17.79%, respectively. The pooled results showed that the pooled PFS of triple therapy was superior to that of the control group (HR=0.74, 95% CI: 0.71-0.77), so was OS (HR=0.68, 95% CI: 0.65-0.72). The pooled rate of any grade AEs was 91.93%, and grade 3 or higher AEs was 34.50%. There were no fatal AEs reported in any of the included studies. The triple therapy of TACE/HAIC combined with ICIs and angiogenesis inhibitors was promising in uHCC with good efficacy and tolerated toxicity; however, the potential influence of confounding factors cannot be entirely excluded.","PeriodicalId":15996,"journal":{"name":"Journal of Immunotherapy","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144208710","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Pembrolizumab Induced Aortitis in a Patient With Head and neck Cancer: A Case Report. Pembrolizumab诱导的头颈癌患者的主动脉炎：1例报告。

IF 3.2 4区医学

Journal of Immunotherapy Pub Date : 2025-06-02 DOI: 10.1097/CJI.0000000000000567

Erum Zaidi, Ningjing Li, Harshit Khosla, Syed H Jafri

引用次数: 0

Immune Profiling of Uveal Melanoma Liver Metastases and Response to Checkpoint Inhibitors. 葡萄膜黑色素瘤肝转移的免疫分析和对检查点抑制剂的反应。

IF 3.2 4区医学

Journal of Immunotherapy Pub Date : 2025-06-01 Epub Date: 2025-04-15 DOI: 10.1097/CJI.0000000000000558

Yusra F Shao, Yasmine Baca, Andrew Hinton, Joanne Xiu, Ari VanderWalde, Matthew Hadfield, Soo J Park, Sourat Darabi, Takami Sato, Justin C Moser

{"title":"Immune Profiling of Uveal Melanoma Liver Metastases and Response to Checkpoint Inhibitors.","authors":"Yusra F Shao, Yasmine Baca, Andrew Hinton, Joanne Xiu, Ari VanderWalde, Matthew Hadfield, Soo J Park, Sourat Darabi, Takami Sato, Justin C Moser","doi":"10.1097/CJI.0000000000000558","DOIUrl":"https://doi.org/10.1097/CJI.0000000000000558","url":null,"abstract":"Responses to immune checkpoint inhibitors (ICIs) differ significantly between uveal melanoma (UM) and cutaneous melanoma (CM) patients. We investigated the immune profile of metastatic UM(mUM) patients and identified markers that are predictive of improved survival. Metastatic liver samples from 189 UM patients and 48 CM patients were analyzed at genomic and transcriptional levels, and survival analysis was performed on a subgroup of 76 ICI-treated mUM patients. UM liver metastases seem to preserve the genomic and immune characteristics of primary UM (pUM), with a low prevalence of ICI markers and high mutation rates of GNA11, GNAQ, BAP1, and SF3B. Compared with mCM, UM liver metastasis showed lower infiltration of several immune cells, but a greater proportion of M2 macrophages. Compared with UM liver metastases, CM liver metastases showed higher expression of G2M checkpoint and EF2 target genes. Among the mUM and mCM samples, expression of G2M and E2F pathway genes was highest in tumors with high TMB values and T-cell inflamed scores. A longer median overall survival (OS) was observed in mUM patients with higher expression of LAG3, HLA class I, or HLA class II; which may represent a small proportion of immune hot tumors. Expression patterns of G2M checkpoint and E2F targets suggest a possible contribution to immunotherapy response.","PeriodicalId":15996,"journal":{"name":"Journal of Immunotherapy","volume":"48 5","pages":"189-195"},"PeriodicalIF":3.2,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12052074/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144022437","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

High Expression of Calreticulin Affected the Tumor Microenvironment and Correlated With Worse Prognosis in Patients With Triple-Negative Breast Cancer. 高表达钙网蛋白影响三阴性乳腺癌患者肿瘤微环境并与不良预后相关

IF 3.2 4区医学

Journal of Immunotherapy Pub Date : 2025-06-01 Epub Date: 2025-03-24 DOI: 10.1097/CJI.0000000000000553

Xi Cao, Xinyu Ren, Yu Song, Qiang Sun, Feng Mao, Songjie Shen, Chang Chen, Yidong Zhou

{"title":"High Expression of Calreticulin Affected the Tumor Microenvironment and Correlated With Worse Prognosis in Patients With Triple-Negative Breast Cancer.","authors":"Xi Cao, Xinyu Ren, Yu Song, Qiang Sun, Feng Mao, Songjie Shen, Chang Chen, Yidong Zhou","doi":"10.1097/CJI.0000000000000553","DOIUrl":"10.1097/CJI.0000000000000553","url":null,"abstract":"Calreticulin (CALR) preserves reticular homeostasis by maintaining correct protein folding within the endoplasmic reticulum. Immunogenic cell death (ICD) is a regulated form of cell death and could activate adaptive immune response. As one of the damage-associated molecular patterns during ICD process, surface-exposed CALR resulted in the activation of adaptive immune response. Here, we evaluated the expression patterns of CALR in a cohort of 231 untreated triple-negative breast cancer (TNBC) and determined correlations between CALR expression and clinicopathologic parameters, programmed cell death ligand 1 (PD-L1) expression in immune cells (ICs), and survival. In addition, we analyzed a TNBC data set from The Cancer Genome Atlas to explore the relationship between mRNA expression of CALR and clinicopathologic features, IC infiltration, and survival. Tissue microarray results showed that high CLAR was strongly correlated with advanced stage ( P = 0.022), shorter disease-free survival ( P = 0.008) and overall survival ( P = 0.002), and independently predicted prognosis in TNBC. Spearman analyses demonstrated that CALR negatively correlated with PD-L1 in ICs ( r = -0.198, P = 0.003). Patients with low CALR and high PD-L1 in ICs had the best disease-free survival ( P = 0.013) and overall survival ( P = 0.004) compared with other patients, especially the patients with high CALR and low PD-L1 in ICs. In the \"The Cancer Genome Atlas\" cohort, CALR mRNA expression in tumors was significantly higher than that in normal tissues ( P < 0.001). CALR expression was strongly and positively related to other ICD-related genes. These findings demonstrated that the expression of CALR could independently predict the prognosis in patients with TNBC, and it may play a potential synergistic role in treatments involving immunotherapy.","PeriodicalId":15996,"journal":{"name":"Journal of Immunotherapy","volume":" ","pages":"173-182"},"PeriodicalIF":3.2,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12052058/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143692408","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Identification of Endoplasmic Reticulum Stress-related Genes for Predicting Prognosis, Immunotherapy Response, and Drug Sensitivity in Thyroid Cancer. 内质网应激相关基因对甲状腺癌预后、免疫治疗反应和药物敏感性的预测。

IF 3.2 4区医学

Journal of Immunotherapy Pub Date : 2025-06-01 Epub Date: 2025-03-26 DOI: 10.1097/CJI.0000000000000554

Lu Zhao, Shuangmei Zhu, Wenxia Ye, Lifen Chen

{"title":"Identification of Endoplasmic Reticulum Stress-related Genes for Predicting Prognosis, Immunotherapy Response, and Drug Sensitivity in Thyroid Cancer.","authors":"Lu Zhao, Shuangmei Zhu, Wenxia Ye, Lifen Chen","doi":"10.1097/CJI.0000000000000554","DOIUrl":"10.1097/CJI.0000000000000554","url":null,"abstract":"ER stress has emerged as a promising target for cancer therapy. RNA sequencing data of patients with THCA were obtained from the TCGA database to identify differentially expressed genes associated with ER stress. Signature genes were selected through univariate Cox regression, LASSO, and multivariate Cox regression analyses. The predictive performance of the model was assessed using Kaplan-Meier survival analysis and ROC curves. GSEA was conducted to explore pathway enrichment between high-risk and low-risk groups. The immune landscape of risk groups was characterized using ssGSEA, ESTIMATE and CIBERSORT algorithms. Quantitative real-time PCR was employed to investigate the mRNA expression of the signature genes. Finally, immunotherapy response and potential drug sensitivity were evaluated. The prognostic model based on the signature genes ANK2, APOE, ERP27, FPR2, and NOS1, demonstrated robust predictive performance. GSEA results revealed distinct pathway enrichment patterns in the high-risk and low-risk groups. Furthermore, ssGSEA revealed that low-risk patients exhibited enhanced immune-related functions and increased immune cell infiltration. The RT-qPCR results revealed that in thyroid cancer cells, APOE and ERP27 expression levels were elevated, and ANK1, NOS1, and FPR2 expression levels were decreased. Immunotherapy, as well as Palbociclib and Perifosine, were predicted to be more effective for low-risk patients. Conversely, high-risk patients were more likely to benefit from Axitinib, Imatinib, Nilotinib, and Temsirolimus. This study identified 5 signature genes as potential biomarkers and therapeutic targets for THCA. These findings provide novel insights into the prognosis and targeted therapy of THCA, offering a foundation for furture clinical applications.","PeriodicalId":15996,"journal":{"name":"Journal of Immunotherapy","volume":" ","pages":"159-172"},"PeriodicalIF":3.2,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143710257","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0