Cancer Biotherapy and Radiopharmaceuticals最新文献

{"title":"A Comprehensive Analysis of LYAR in Colorectal Cancer: Prognostic Marker and Therapeutic Target.","authors":"Jia-Ying Wen, Ye-Ying Fang, Dong-Ming Li, Yu-Lu Tang, He-Qing Huang, Li-Min Liu, Jiang-Hui Zeng, Yi-Wu Dang, Yan-Fang Pan, Da-Tong Zeng, Wei-Jian Huang, Gang Chen, Hui Li","doi":"10.1089/cbr.2023.0181","DOIUrl":"10.1089/cbr.2023.0181","url":null,"abstract":"<p><p><b><i>Background:</i></b> Colorectal cancer (CRC) is a major global health challenge with a need for new biomarkers and therapeutic targets. This work investigated the biological mechanisms and clinical value of Ly1 antibody reactive (LYAR) in CRC. <b><i>Methods:</i></b> We analyzed LYAR mRNA expression across multiple public databases, including genotype-tissue expression, gene expression omnibus, Oncomine, and the cancer genome atlas, alongside in-house immunohistochemical data to evaluate LYAR protein expression in CRC and non-CRC colorectal tissues. Gene set enrichment analysis (GSEA) was used to elucidate LYAR's biological functions, and its impact on the tumor immune microenvironment was assessed using CIBERSORT, ESTIMATE, and single-cell RNA sequencing techniques. In addition, LYAR's association with clinicopathological features and patient prognosis was explored, and its influence on drug sensitivity was investigated using the Connectivity Map database. <b><i>Results:</i></b> LYAR was significantly upregulated in CRC tissues compared with non-CRC colorectal counterparts, associated with altered immune cell composition and enhanced RNA processing, splicing, and cell cycle regulation. High LYAR expression correlated with poor disease-free and overall survival, underscoring its prognostic value. GSEA revealed LYAR's involvement in critical cellular processes and pathways, including DNA repair, cell cycle, and mTORC1 signaling. Correlation analysis identified genes positively and negatively associated with LYAR, leading to the discovery of temsirolimus and WYE-354, mTOR inhibitors, as potential therapeutic agents for CRC. Furthermore, LYAR expression predicted increased sensitivity to cetuximab in RAS wild-type metastatic CRC, indicating its utility as a biomarker for treatment responsiveness. <b><i>Conclusions:</i></b> LYAR's upregulation in CRC highlights its potential as a biomarker for prognosis and therapeutic targeting, offering insights into CRC pathology and suggesting new avenues for treatment optimization.</p>","PeriodicalId":55277,"journal":{"name":"Cancer Biotherapy and Radiopharmaceuticals","volume":" ","pages":"673-689"},"PeriodicalIF":2.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142005928","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}

{"title":"Circ-PGAM1 Enhances Matrine Resistance of Non-Small Cell Lung Cancer via the miR-326/CXCR5 Axis.","authors":"Caijun Dong, Liangwei Yang, Guofang Zhao","doi":"10.1089/cbr.2022.0039","DOIUrl":"10.1089/cbr.2022.0039","url":null,"abstract":"<p><p><b><i>Background:</i></b> Circular RNAs (circ-RNAs) have been demonstrated to influence initiation, drug resistance, and metastasis of tumors. However, the effects of circular-phosphoglycerate mutase 1 (circ-PGAM1) on matrine resistance in nonsmall cell lung cancer (NSCLC) remain unknown. <b><i>Materials and Methods:</i></b> The reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to determine gene expression. The terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and cell colony formation assays were used to evaluate NSCLC apoptosis and cell proliferation after indicated treatments, respectively. <b><i>Results:</i></b> circ-PGAM1 was upregulated in human NSCLC cell lines (H1299 and A549) compared with the human normal lung epithelial (BEAS-2B) cells. circ-PGAM1 overexpression reversed the matrine treatment-induced inhibition on proliferation of NSCLC cells (A549 and H1299) and rescued the matrine treatment-stimulated apoptosis of these cells. miR-326 was demonstrated to interact with circ-PGAM1. circ-PGAM1 knockdown enhanced the antitumor effect of matrine on NSCLC cell proliferation and apoptosis, which was reversed by miR-326 inhibition. The authors also identified CXCR5 as a key downstream target of miR-326 in A549 cells. <b><i>Conclusions:</i></b> circ-PGAM1 enhances matrine resistance of NSCLC cells through the miR-326/CXCR5 axis. The authors' findings provide new insights into NSCLC-targeted therapy.</p>","PeriodicalId":55277,"journal":{"name":"Cancer Biotherapy and Radiopharmaceuticals","volume":" ","pages":"593-599"},"PeriodicalIF":2.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10433558","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}

{"title":"Development in the Study of Natural Killer Cells for Malignant Peritoneal Mesothelioma Treatment.","authors":"Yi-Tong Liu, He-Liang Wu, Yan-Dong Su, Yi Wang, Yan Li","doi":"10.1089/cbr.2024.0078","DOIUrl":"10.1089/cbr.2024.0078","url":null,"abstract":"<p><p>Malignant peritoneal mesothelioma (MPeM) is a rare primary malignant tumor originating from peritoneal mesothelial cells. Insufficient specificity of the symptoms and their frequent reappearance following surgery make it challenging to diagnose, creating a need for more efficient treatment options. Natural killer cells (NK cells) are part of the innate immune system and are classified as lymphoid cells. Under the regulation of activating and inhibiting receptors, NK cells secrete various cytokines to exert cytotoxic effects and participate in antiforeign body, antiviral, and antitumor activities. This review provides a comprehensive summary of the specific alterations observed in NK cells following MPeM treatment, including changes in cell number, subpopulation distribution, active receptors, and cytotoxicity. In addition, we summarize the impact of various therapeutic interventions, such as chemotherapy, immunotherapy, and targeted therapy, on NK cell function post-MPeM treatment.</p>","PeriodicalId":55277,"journal":{"name":"Cancer Biotherapy and Radiopharmaceuticals","volume":" ","pages":"551-561"},"PeriodicalIF":2.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141879866","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}

{"title":"MiR-4429 Alleviates Malignant Behaviors of Lung Adenocarcioma Through <i>Wnt/β-Catenin</i> Pathway.","authors":"Shaoqiang Zhou, Kebao Qian, Shuhui Yu, Yutao Zhao, Qin Shen, Ya Li","doi":"10.1089/cbr.2021.0154","DOIUrl":"10.1089/cbr.2021.0154","url":null,"abstract":"<p><p>Lung adenocarcinoma (ADC) is a common subtype of non-small cell lung cancer. MicroRNAs have been reported to be effective biomarkers for diagnosis and an important target for therapy. MiR-4429 is a newly identified miRNA, which can take part in tumor progression as a tumor inhibitor. Moreover, it is an exosomal miRNA that can be taken by lung ADC cell line A549. Nevertheless, its role in lung ADC has been poorly studied. This research discovered that miR-4429 was low expressed in lung ADC cells. MiR-4429 mimics could alleviate the capacities of cell proliferation and metastasis. The mimics are able to reverse epithelial-mesenchymal transition at the same time. Furthermore, it was verified that miR-4429 could bind to <i>β-catenin</i> and negatively regulate <i>β-catenin</i> expression. Interestingly, SKL2001 can reverse the role of miR-4429 on tumor. Consequently, miR-4429 can inactivate <i>Wnt/β-catenin</i> signaling pathway by targeting <i>β-catenin</i> and prevent oncogene expression in lung ADC cells.</p>","PeriodicalId":55277,"journal":{"name":"Cancer Biotherapy and Radiopharmaceuticals","volume":" ","pages":"562-572"},"PeriodicalIF":2.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39391598","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}

{"title":"Long Noncoding RNAs PTPRG Antisense RNA 1 Targets Cyclin D1 to Facilitate Cell Proliferation in Lung Adenocarcinoma.","authors":"Yang Xue, Mingqiang Diao, Jing Lyu, Kang Li, Long He, Junfeng Chen, Xiangguo Li","doi":"10.1089/cbr.2021.0168","DOIUrl":"10.1089/cbr.2021.0168","url":null,"abstract":"<p><p><b><i>Background:</i></b> Numerous studies have recorded the function of long noncoding RNAs (lncRNAs) in cancer development, including lung adenocarcinoma (LUAD). Previous studies have reported the crucial role of lncRNA PTPRG antisense RNA 1 (PTPRG-AS1) in various cancers. However, the role of PTPRG-AS1 in LUAD remains unknown. <b><i>Materials and Methods:</i></b> Real-time quantitative polymerase chain reaction (RT-qPCR) was applied for detecting PTPRG-AS1 expression in LUAD cell lines. Functional assays and <i>in vivo</i> experiments explored cell proliferation, whereas flow cytometry analysis was used to detect cell cycle. In addition, fluorescent <i>in situ</i> hybridization (FISH) and subcellular fractionation assay measured the localization of PTPRG-AS1 in LUAD cells. RNA pulldown, luciferase reporter, and RNA immunoprecipitation (RIP) assays were used to investigate the interaction of PTPRG-AS1/miR-124-3p/cyclin D1 (<i>CCND1</i>) axis. <b><i>Results:</i></b> PTPRG-AS1 expression was notably high in LUAD cell lines. PTPRG-AS1 knockdown suppressed cell proliferation and cycle as well as the level of <i>CCND1</i>. Moreover, miR-124-3p was the mutual target of PTPRG-AS1 and <i>CCND1</i>. In addition, PTPRG-AS1 sponged miR-124-3p to upregulate <i>CCND1</i> in LUAD cells. Moreover, miR-124-3p depletion reversed the suppression of PTPRG-AS1 silence on LUAD cell behaviors, but then <i>CCND1</i> knockdown countervailed the promoting influence of downregulated miR-124-3p. <b><i>Conclusions:</i></b> PTPRG-AS1 propels cell proliferation and cell cycle of LUAD by targeting miR-124-3p/<i>CCND1</i> axis.</p>","PeriodicalId":55277,"journal":{"name":"Cancer Biotherapy and Radiopharmaceuticals","volume":" ","pages":"573-583"},"PeriodicalIF":2.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39882219","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}

{"title":"Dihydroartemisinin Inhibits Epithelial-Mesenchymal Transition Progression in Medullary Thyroid Carcinoma Through the Hippo Signaling Pathway Regulated by Interleukin-6.","authors":"Ruicong Li,Xinyu Zhang,Yanan Ge,Zhen Zhao,Liangliang Feng,Xiaoming Li","doi":"10.1089/cbr.2023.0197","DOIUrl":"https://doi.org/10.1089/cbr.2023.0197","url":null,"abstract":"Dihydroartemisinin (DHA), an artemisinin derivative, can influence certain malignancies' inflammatory response and growth. This study used Cell Counting Kit-8 and Transwell assays to show that DHA suppressed the growth, migration, and invasion of medullary thyroid cancer cells. Furthermore, the authors used enzyme-linked immunosorbent assay, Western blotting, and immunofluorescence to confirm the expression of the transcriptional coactivators Yes-associated protein (YAP)/transcriptional coactivator with a PDZ-binding domain (TAZ) downstream of the Hippo pathway and changes in the expression of the epithelial-mesenchymal transition (EMT) process markers E-cadherin and N-cadherin. These results demonstrate that DHA effectively reduced the expression of interleukin (IL)-6 in medullary thyroid carcinoma (MTC) cells and hindered the EMT process by regulating the Hippo pathway. This regulation was achieved by promoting YAP phosphorylation and inhibiting YAP/TAZ protein expression. Additional activation of the Hippo pathway by GA-017 alleviated the inhibitory effect of DHA on IL-6. Hippo pathway activation led to an increase in the expression of E-cadherin, a marker of EMT. In conclusion, DHA was demonstrated to regulate the Hippo pathway by inhibiting IL-6 secretion, leading to the inhibition of EMT in MTC. These findings provide a theoretical foundation for further exploration of the anticancer mechanisms of DHA and offer valuable insights into its potential clinical application as a combinatorial drug.","PeriodicalId":55277,"journal":{"name":"Cancer Biotherapy and Radiopharmaceuticals","volume":"213 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142257369","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}

{"title":"Synthesis, Preclinical Toxicity, and Biodistribution of [18F]AVT-011 to Assess the P-Glycoprotein Function.","authors":"Riptee Thakur,Manoj Kumar,Aishwarya Kumar,Raman Kumar Joshi,Divya Maheshwari,Afsal Mohammed Km,Manjunatha Venkataswamy,Bhabani Mohanty,Pradip Chaudhari,Hosahalli K Mohan,Pardeep Kumar","doi":"10.1089/cbr.2024.0114","DOIUrl":"https://doi.org/10.1089/cbr.2024.0114","url":null,"abstract":"Introduction: Many studies have reported the role of P-glycoprotein (Pgp) in chemoresistance in various pathological conditions such as cancer and neurodegenerative diseases, such as Alzheimer's. In this study, we are reporting the high-performance liquid chromatography (HPLC)-based purification of fluorine-18 [18F]AVT-011 and its preclinical evaluation. Methods: AVT-011 was labeled with 18F using the nucleophilic substitution method by heating the reaction mixture at 110°C for 10 min, followed by purification using preparative HPLC and C18ec cartridge. The in vitro cell uptake study was carried out in U87 cells with and without an inhibitor. The preclinical toxicity was carried out in CD1 mice in three groups, including control, AVT-011 treated, and [18F]AVT-011 treated. The biodistribution study was done in CD1 mice (n = 12) after intravenous injection of 4-6 MBq [18F]AVT-011, and mice were sacrificed at various time intervals. A dose of 3.7 ± 0.7 MBq of [18F]AVT-011 was injected intravenously in the healthy Swiss albino mice, and the whole-body micro-positron emission tomography was acquired at 0-, 30-, 60-, and 120-min postinjection. Results: The radiochemical purity of [18F]AVT-011 was 97 ± 1.5% as evaluated by radio-HPLC with a yield of 14 ± 2% and was stable up to 95% under in vitro conditions in blood and in vivo conditions up to 4 h. The in vitro cell uptake study showed a significant difference in control (27.4 ± 2.1%) and blocked U987 cells (73.2 ± 3.2%) after incubation of 120 min. The tissue distribution in mice showed the highest uptake in the liver (17.3 ± 2.4%), kidneys (16.6 ± 3.1%), lungs (10.4 ± 2.9%), and spleen (5.6 ± 0.8%) at 15 min, and the activity was washed out with time. The radioactivity cleared through the hepatorenal pathway. The animal imaging study also demonstrates a similar biodistribution pattern. Conclusions: [18F]AVT-011 showed higher specific activity than the cartridge-based method but showed similar biological activity.","PeriodicalId":55277,"journal":{"name":"Cancer Biotherapy and Radiopharmaceuticals","volume":"164 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142194030","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}

{"title":"Colorectal Cancer-Derived Exosomes Impair CD4+ T Cell Function and Accelerate Cancer Progression via Macrophage Activation.","authors":"Xiaolong Wang,Liang Chen,Wenwei Zhang,Wei Sun,Jianpeng Huang","doi":"10.1089/cbr.2024.0032","DOIUrl":"https://doi.org/10.1089/cbr.2024.0032","url":null,"abstract":"Background: Exosomal programmed death ligand 1 (PD-L1), an exosomal membrane protein found in many tumor types, is reckoned to help regulate the immune microenvironment. However, the functions and the mechanisms underlying the exosome-mediated regulation of the immune microenvironment in colorectal cancer (CRC) remain unknown. Methods: Western blotting was used to investigate the levels of exosomal PD-L1 in the peripheral blood of patients with CRC and healthy controls. A CRC mouse model was constructed by administering 10 mg/kg azoxymethane (AOM) and dextrane sodium sulfate (DSS) intraperitoneally. The mice were then administered the control or CRC-derived exosomes to examine the regulatory effect of the exosomes on macrophage infiltration and CRC development. In vitro studies, using a coculture system, and flow cytometry analysis were conducted to examine the relationship between the regulatory effect of CRC-derived exosomes on CD4+ T cells and tumor-associated macrophages. RNA-seq and reverse transcription-quantitative polymerase chain reaction assays were used to investigate the mechanisms underlying the regulatory effect of the CRC-derived exosomes on macrophage proliferation and the regulation of the immune microenvironment during CRC development. Results: In patients with CRC, higher levels of exosomal PD-L1 were associated with a more severe form of disease. The treatment of mice with AOM/DSS-induced CRC with CRC-derived exosomes resulted in high levels of macrophage proliferation, increased PD-L1 levels in macrophages, and accelerated CRC progression. Importantly, analysis of an in vitro coculture system and flow cytometry analysis showed that the CRC-derived exosomes transported PD-L1 into macrophages and impaired CD4+ T cell function. Preliminary data suggest that the NF-κb signaling pathway regulates the function of CRC-derived exosomal PD-L1-dependent macrophages. Conclusion: CRC-derived exosomes induce the proliferation of macrophages and increase their PD-L1 levels. They also impair CD4+ T cell function and promote CRC progression. Our findings reveal a novel exosomal PD-L1-mediated crosstalk between the CRC cells and immune cells in the CRC microenvironment.","PeriodicalId":55277,"journal":{"name":"Cancer Biotherapy and Radiopharmaceuticals","volume":"25 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142194029","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}

{"title":"METTL3-Mediated m6A Modification of FMRP Drives Hepatocellular Carcinoma Progression and Indicates Poor Prognosis.","authors":"Siyuan Fu,Dapeng Sun,Zongyan Wang,Peng Zhu,Wenbin Ding,Jian Huang,Xinggang Guo,Yun Yang,Fangming Gu","doi":"10.1089/cbr.2023.0186","DOIUrl":"https://doi.org/10.1089/cbr.2023.0186","url":null,"abstract":"Accumulating studies reveal that m6A RNA methylation plays a critical role in cancer pathogenesis and progression. METTL3 as a m6A methyltransferase acts as an oncogene in multiple malignancies including hepatocellular carcinoma (HCC). However, the role and underlying mechanism by which METTL3 contributes to HCC remain unclear. The association of METTL3 expression with clinicopathological characteristics and prognosis in patients with HCC was assessed by reverse transcription polymerase chain reaction, Western blot, and public TCGA dataset. MTT, colony formation, Transwell assays, and xenograft tumor models were executed to reveal the role of METTL3 in HCC. m6A dot blot, RNA immunoprecipitation (RIP), m6A methylated RIP, and Western blot assays were used to uncover the regulatory mechanism of METTL3 in HCC cells. We found that METTL3 was dramatically upregulated in HCC tissue samples and acted as an independent prognostic factor for poor survival and tumor recurrence in patients with HCC. Silencing of METTL3 repressed cell growth and invasion in vitro and in vivo, but restored expression of METTL3 boosted these effects. Mechanistical investigations revealed that METTL3 could directly interact with FMRP and harbor a positive correlation with FMRP expression. Knockdown of METTL3 reduced FMRP m6A levels as well as its mRNA and protein expression. FMRP overexpression drove cell colony formation and cell invasion and abolished METTL3 knockdown-induced antitumor effects and AKT/mTORC1 signaling inactivation. Elevated expression of FMRP could act as an independent prognostic factor for poor survival and tumor recurrence in patients with HCC. Our findings demonstrate that METTL3-mediated m6A modification of FMRP promotes growth and invasion of HCC cells and may provide a promising therapeutic target for HCC.","PeriodicalId":55277,"journal":{"name":"Cancer Biotherapy and Radiopharmaceuticals","volume":"37 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142194028","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}

{"title":"Prognostic Signature in Osteosarcoma Based on Amino Acid Metabolism-Associated Genes.","authors":"Liwen Feng, Yuting Chen, Xiangping Mei, Lei Wang, Wenjing Zhao, Jiannan Yao","doi":"10.1089/cbr.2024.0002","DOIUrl":"10.1089/cbr.2024.0002","url":null,"abstract":"<p><p><b><i>Background:</i></b> Osteosarcoma (OS) is undeniably a formidable bone malignancy characterized by a scarcity of effective treatment options. Reprogramming of amino acid (AA) metabolism has been associated with OS development. The present study was designed to identify metabolism-associated genes (MAGs) that are differentially expressed in OS and to construct a MAG-based prognostic risk signature for this disease. <b><i>Methods:</i></b> Expression profiles and clinicopathological data were downloaded from Gene Expression Omnibus (GEO) and UCSC Xena databases. A set of AA MAGs was obtained from the MSigDB database. Differentially expressed genes (DEGs) in GEO dataset were identified using \"limma.\" Prognostic MAGs from UCSC Xena database were determined through univariate Cox regression and used in the prognostic signature development. This signature was validated using another dataset from GEO database. Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, single sample gene set enrichment analysis, and GDSC2 analyses were performed to explore the biological functions of the MAGs. A MAG-based nomogram was established to predict 1-, 3-, and 5-year survival. Real-time quantitative polymerase chain reaction, Western blot, and immunohistochemical staining confirmed the expression of MAGs in primary OS and paired adjacent normal tissues. <b><i>Results:</i></b> A total of 790 DEGs and 62 prognostic MAGs were identified. A MAG-based signature was constructed based on four MAGs: <i>PIPOX</i>, <i>PSMC2</i>, <i>SMOX</i>, and <i>PSAT1</i>. The prognostic value of this signature was successfully validated, with areas under the receiver operating characteristic curves for 1-, 3-, and 5-year survival of 0.714, 0.719, and 0.715, respectively. This MAG-based signature was correlated with the infiltration of CD56^dim natural killer cells and resistance to several antiangiogenic agents. The nomogram was accurate in predictions, with a C-index of 0.77. The expression of MAGs verified by experiment was consistent with the trends observed in GEO database. <b><i>Conclusion:</i></b> Four AA MAGs were prognostic of survival in OS patients. This MAG-based signature has the potential to offer valuable insights into the development of treatments for OS.</p>","PeriodicalId":55277,"journal":{"name":"Cancer Biotherapy and Radiopharmaceuticals","volume":" ","pages":"517-531"},"PeriodicalIF":2.4,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140186385","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}