Yinghui Zhi, Wenshan Zhang, Zhenyu Wu, Yan Chen, Liang Feng, Jing He, Feng Wang, Huan Liu
{"title":"miR-223-3p Targets <i>KIF4A</i> and Promotes the Oxidative Stress-Mediated Apoptosis of Breast Cancer Cells.","authors":"Yinghui Zhi, Wenshan Zhang, Zhenyu Wu, Yan Chen, Liang Feng, Jing He, Feng Wang, Huan Liu","doi":"10.1089/cbr.2024.0102","DOIUrl":"https://doi.org/10.1089/cbr.2024.0102","url":null,"abstract":"<p><p><b><i>Background:</i></b> The abnormal expression of kinase family member 4A (<i>KIF4A</i>) is linked to breast cancer progression, with numerous miRNAs exhibiting abnormal expression. Thus, there is an urgent need to investigate the mechanisms of action of miRNAs and their target genes for the diagnosis and treatment of breast cancer. <b><i>Materials and Methods:</i></b> A bioinformatics analysis was conducted to screen for <i>KIF4A</i>, a key gene involved in oxidative stress in breast cancer cells. Using CCK8, EdU, cell healing, and Transwell assays, the knockdown of <i>KIF4A</i> was found to effectively inhibit the proliferation, migration, and invasion of breast cancer cells. Dual-luciferase assay and Western blotting confirmed that miR-223-3p targets and regulates <i>KIF4A</i> expression. The impact of miR-223-3p and <i>KIF4A</i> on oxidative stress in breast cancer cells was assessed through reactive oxygen species (ROS), superoxide dismutase (SOD), and malondialdehyde (MDA) measurements. Flow cytometry was used to evaluate tumor cell apoptosis. <b><i>Results:</i></b> Our results suggest that <i>KIF4A</i> is a downstream target of miR-223-3p. miR-223-3p inhibits the proliferation and invasion of breast cancer cells by directly targeting and downregulating <i>KIF4A</i>. Importantly, we found that miR-223-3p and <i>KIF4A</i> play important roles in regulating oxidative stress and apoptosis in breast cancer cells. Specifically, miR-223-3p promoted apoptosis by inhibiting the expression of <i>KIF4A</i>, increasing the accumulation level of ROS and MDA, and inhibiting the activity of SOD while <i>KIF4A</i> was overexpressed.</p>","PeriodicalId":55277,"journal":{"name":"Cancer Biotherapy and Radiopharmaceuticals","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143366846","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}
Christina Ward, Sandon Scott, William Wesson, Jared Mazurek, Ian Kozlowski, Gregg Werner, Arshan Dehbozorgi, Milind Phadnis, Carissa Walter, Aaron Rohr, Zachary Collins
{"title":"Dosimetry Assessment in Predicting Treatment Outcomes Following Yttrium-90 Transarterial Radioembolization of Hepatic Tumors.","authors":"Christina Ward, Sandon Scott, William Wesson, Jared Mazurek, Ian Kozlowski, Gregg Werner, Arshan Dehbozorgi, Milind Phadnis, Carissa Walter, Aaron Rohr, Zachary Collins","doi":"10.1089/cbr.2024.0194","DOIUrl":"https://doi.org/10.1089/cbr.2024.0194","url":null,"abstract":"<p><p><b><i>Purpose:</i></b> To evaluate the use of yttrium-90 (Y90) dosimetry in predicting treatment outcomes when used following transarterial radioembolization with SIR-Spheres® (Resin Y90) in patients with hepatic tumors. <b><i>Materials and Methods:</i></b> This single institution retrospective analysis included 100 patients with hepatocellular carcinoma, colorectal carcinoma or other liver metastases who underwent transarterial radioembolization with resin Y90 and had imaging follow-up within one year of treatment. Mean tumor dose and mean dose to nontumor was calculated using voxel-based dosimetry software. Descriptive statistics were reported and methods of analyses included simple and multivariable linear regression, contingency table analyses, Kaplan-Meier estimation, and Cox proportional hazards models. <b><i>Results:</i></b> Of 100 patients included, 65 demonstrated tumor shrinkage following transarterial radioembolization. Of these, 20 (30.8%) had hepatocellular carcinoma, 22 (33.8%) had colorectal carcinoma, and 23 (35.4%) had other types of metastases. There was an association between tumor shrinkage and mean tumor dose (<i>p</i> = 0.0285) and mean dose to nontumor (<i>p</i> = 0.0028) in hepatocellular carcinoma patients, but not colorectal carcinoma, or the other subgroup. For all 100 patients, time to death and mean tumor dose was associated only in the other subgroup (<i>p</i> = 0.0260), but not in the hepatocellular or colorectal carcinoma groups. Time to death and mean dose to nontumor was associated in hepatocellular carcinoma patients (<i>p</i> = 0.0421), but not the colorectal carcinoma or other subgroup. <b><i>Conclusions:</i></b> Voxel-based dosimetry assessment is a tool that may be utilized to assist in predicting treatment outcomes in responders to transarterial radioembolization.</p>","PeriodicalId":55277,"journal":{"name":"Cancer Biotherapy and Radiopharmaceuticals","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143069564","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}
Gündüzalp Buğrahan Babacan, Filiz Özülker, Oğuzhan Şahin, Osman Güven, Osman Kanatsız, Göksel Alçın, Tamer Özülker
{"title":"Is There Novel <sup>18</sup>F-FDG Biodistribution in the Digital PET/CT Era? A Real-World Data Analysis.","authors":"Gündüzalp Buğrahan Babacan, Filiz Özülker, Oğuzhan Şahin, Osman Güven, Osman Kanatsız, Göksel Alçın, Tamer Özülker","doi":"10.1089/cbr.2024.0226","DOIUrl":"https://doi.org/10.1089/cbr.2024.0226","url":null,"abstract":"<p><p><b><i>Background:</i></b> This retrospective multicenter study investigated the biodistribution of Fluorodeoxyglucose (<sup>18</sup>F-FDG) in the positron emission tomography (PET)/computed tomography (CT) in digital PET/CT (dPET) compared to analog PET/CT (aPET), focusing differences in physiological uptake in reference and small structures across various scanner models. <b><i>Materials and Methods:</i></b> One hundred thirty patients with similar preimaging conditions underwent both dPET and aPET imaging within 6 months. Visual evaluations and paired comparative analyses of semiquantitative parameters were performed for small and reference structures. <b><i>Results:</i></b> <sup>18</sup>F-FDG uptake was higher in both reference and small structures for dPET compared to three different aPET scanners. The Siemens mCT20-4R (mCT20) demonstrated comparable results to dPET. Notably, mCT20 had higher standardized uptake value (SUV<sub>max</sub>) for the conus medullaris (CM) (3.20 vs. 2.76). CM was most highly visible with dPET on visual evaluation by physicians. <b><i>Conclusions:</i></b> Digital PET/CT provides higher SUV values in both small and reference structures. This leads to improved visualization of <sup>18</sup>F-FDG physiological biodistribution. Given the growing adoption of dPET technology, these advancements should be carefully considered in image interpretation and clinical research.</p>","PeriodicalId":55277,"journal":{"name":"Cancer Biotherapy and Radiopharmaceuticals","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143048842","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}
Srinivas Ananth Kumar, Ashwani Sood, Rajender Kumar, Somit Pandey, Jaya Shukla, Bhagwant Rai Mittal, Stanley Satz
{"title":"Exploring the Role of [<sup>68</sup>Ga]Ga-DOTAGA-IAC and Comparison of Its Diagnostic Performance with [<sup>18</sup>F]F-FDG PET/CT in Radioiodine Refractory Differentiated Thyroid Carcinoma.","authors":"Srinivas Ananth Kumar, Ashwani Sood, Rajender Kumar, Somit Pandey, Jaya Shukla, Bhagwant Rai Mittal, Stanley Satz","doi":"10.1089/cbr.2024.0166","DOIUrl":"https://doi.org/10.1089/cbr.2024.0166","url":null,"abstract":"<p><p><b><i>Introduction:</i></b> Integrin antagonist complex (IAC), a novel αvβ3 integrin antagonist peptidomimetic, has emerged as a promising agent for molecular imaging of tumor angiogenesis. This study evaluates the biodistribution and clinical efficacy of [<sup>68</sup>Ga]Ga-DOTAGA-IAC PET/CT in detecting radioiodine-refractory differentiated thyroid carcinoma (RAIR-DTC), comparing its diagnostic performance with [<sup>18</sup>F]F-FDG PET/CT. <b><i>Materials and Methods:</i></b> In this prospective pilot study, RAIR-DTC patients underwent whole-body imaging with [<sup>18</sup>F] F-FDG PET/CT, followed by [<sup>68</sup>Ga]Ga-DOTAGA-IAC PET/CT. Biodistribution patterns of [<sup>68</sup>Ga]Ga-DOTAGA-IAC were assessed. Lesions with abnormal, nonphysiologic tracer uptake (showing activity exceeding mediastinal blood pool) were considered positive for disease. Imaging findings were compared between the two modalities, and quantitative metrics, including SUV<sub>max</sub>, metabolic tumor volume, and total lesion glycolysis, were analyzed statistically. <b><i>Results:</i></b> Among 30 patients with RAIR-DTC, [<sup>68</sup>Ga]Ga-DOTAGA-IAC PET/CT revealed predominant physiological tracer uptake in the kidneys. [<sup>18</sup>F]F-FDG PET/CT identified 97 lesions, predominantly nodal (73.2%), while [<sup>68</sup>Ga]Ga-DOTAGA-IAC PET/CT detected 34 lesions, 50% of which were nodal. Few patients exhibited multiple lesions with varying uptake grades, with 20% showing coexisting higher-grade lesions (grade II or above) on [<sup>68</sup>Ga]Ga-DOTAGA-IAC PET/CT. <b><i>Conclusion:</i></b> Angiogenesis imaging using [<sup>68</sup>Ga]Ga-DOTAGA-IAC PET/CT demonstrates limited sensitivity for lesion detection in patients with RAIR-DTC compared with [<sup>18</sup>F]F-FDG PET/CT. However, the potential of [<sup>68</sup>Ga]Ga-DOTAGA-IAC as a diagnostic tool for other cancers has been used in other cancers with positive imaging characteristics warranting further exploration.</p>","PeriodicalId":55277,"journal":{"name":"Cancer Biotherapy and Radiopharmaceuticals","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142973406","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":"Stratification of Lung Adenocarcinoma Patients Based on <i>In Silico</i> and Immunohistochemistry Analyses of Oxidative Stress-Related Genes.","authors":"Chongrong Qiu, Yuming Zhou, Xiaoliu Xiao, Tianjun Song, Dongyun Zeng, Jingliang Peng","doi":"10.1089/cbr.2024.0094","DOIUrl":"10.1089/cbr.2024.0094","url":null,"abstract":"<p><p><b><i>Background:</i></b> Lung adenocarcinoma (LUAD) remains heterogeneous in the prognosis of patients; oxidative stress (OS) has been widely linked to cancer progression. Therefore, it is necessary to explore the prognostic value of the OS-associated genes in LUAD. <b><i>Methods:</i></b> An OS-associated prognostic signature was developed using the Cox regression and random forest model in The Cancer Genome Atlas-LUAD dataset. Kaplan-Meier <b>(K-M)</b> survival curve and time-dependent receiver operating characteristic (tROC) curves were applied to evaluate and validate the predictive accuracy of this signature among the training and testing cohorts. A nomogram was constructed and also verified by the concordance index (C-index), calibration curves, and tROC curves, respectively. ESTIMATE algorithm and CIBERSORT algorithms were conducted to explore the signature's immune characteristics. Core target genes of the prognostic signature were identified in the protein-protein interaction network. <b><i>Results:</i></b> A six OS-associated prognostic gene signature (<i>CDC25C, ERO1A, GRIA1, TERT, CAV1, BDNF</i>) was developed. The tROC and K-M survival curves in the training and testing cohorts revealed that the signature had good and robust predictive capability to predict the overall survival of LUAD patients. Meanwhile, the risk score was an independent prognostic factor influencing patients' overall survival. The results of the C-index (0.714), calibration curves, and the 1-, 2-, and 3-year tROC curves (area under the curve = 0.703, 0.737, and 0.723, respectively) suggested that the nomogram had good predictive efficacy and prognostic value for LUAD. Then, the authors found that the high-risk group may be depletion or loss of antitumor function of immune cells. Finally, 10 core genes of the signature were predicted. <b><i>Conclusion:</i></b> Their study may provide a novel understanding for the identification of prognostic stratification in LUAD patients, as well as the regulation of OS-associated genes in LUAD progression.</p>","PeriodicalId":55277,"journal":{"name":"Cancer Biotherapy and Radiopharmaceuticals","volume":" ","pages":"11-21"},"PeriodicalIF":2.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141478034","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}
Huan Zhang, Paul Winter, Thomas Wartmann, Luca Simioni, Sara Al-Madhi, Aris Perrakis, Roland S Croner, Wenjie Shi, Quan Yu, Ulf D Kahlert
{"title":"Unlocking Clinical Insights: Lymphocyte-Specific Protein Tyrosine Kinase Candidates as Promising Therapeutic Targets for Pancreatic Cancer Risk Stratification.","authors":"Huan Zhang, Paul Winter, Thomas Wartmann, Luca Simioni, Sara Al-Madhi, Aris Perrakis, Roland S Croner, Wenjie Shi, Quan Yu, Ulf D Kahlert","doi":"10.1089/cbr.2024.0056","DOIUrl":"10.1089/cbr.2024.0056","url":null,"abstract":"<p><p><b><i>Background:</i></b> Uncover the pivotal link between lymphocyte-specific protein tyrosine kinase (Lck)-related genes and clinical risk stratification in pancreatic cancer. <b><i>Methods:</i></b> This study identifies shared genes between differentially expressed genes (DEGs) and Lck-related genes in pancreatic cancer using a methodological framework rooted in The Cancer Genome Atlas database. Feature gene selection is accomplished and a signature model is constructed. Statistical significant clinical endpoints such as overall survival (OS), disease-specific survival (DSS), and progression-free interval (PFI) were defined. <b><i>Results:</i></b> After performing random survival forest, Lasso regression, and multivariate Cox regression model, 7 trait genes out of 272 Lck-associated DEGs are selected to create a signature model that is independent of other clinical factors and can predict OS and DSS. It appears that high-risk patients have activated the TP53 signaling pathway and the cell cycle signaling pathway. <i>LAMA3</i> turned out to be the hub gene of the signature with high expression in pancreatic cancer. Patients with increased expression of <i>LAMA3</i> had a short OS, DSS, and PFI in comparison. The candidate competing endogenous RNA network of <i>LAMA3</i> turned out to be OPI5-AS1/hsa-miR-186-5p/<i>LAMA3</i> axis. <b><i>Conclusions:</i></b> A characteristic signature of seven Lck-related genes, especially <i>LAMA3</i>, has been shown to be a key factor in clinical risk stratification for pancreatic cancer.</p>","PeriodicalId":55277,"journal":{"name":"Cancer Biotherapy and Radiopharmaceuticals","volume":" ","pages":"1-10"},"PeriodicalIF":2.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141263640","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}
Junguo Chen, Yanhong Zhang, Xijie Chen, Dandong Luo, Danlin Liu, Zhaoliang Yu, Yanyun Lin, Xiaosheng He, Juanni Huang, Lei Lian
{"title":"Raddeanin A Inhibits Colorectal Cancer Growth and Ameliorates Oxaliplatin Resistance Through the WNT/β-Catenin Signaling Pathway.","authors":"Junguo Chen, Yanhong Zhang, Xijie Chen, Dandong Luo, Danlin Liu, Zhaoliang Yu, Yanyun Lin, Xiaosheng He, Juanni Huang, Lei Lian","doi":"10.1089/cbr.2024.0061","DOIUrl":"10.1089/cbr.2024.0061","url":null,"abstract":"<p><p><b><i>Background:</i></b> Chemotherapy based on oxaliplatin (OXA) is the first-line treatment for advanced colorectal cancer (CRC), and acquired resistance to OXA is the main reason for clinical treatment failure in CRC. <b><i>Methods:</i></b> To search for compounds that can reverse OXA resistance, we screened a small molecule inhibitor drug library and identified a drug, Raddeanin A (RA), that enhanced the anticancer effect of OXA. Using human CRC cell lines, CRC organoid models, and <i>in vivo</i> subcutaneous tumorigenic studies, we determined that RA inhibits the proliferation of CRC cells by promoting apoptosis and inducing cell cycle arrest. <b><i>Results:</i></b> We constructed OXA-resistant CRC cell lines and demonstrated that RA enhances the sensitivity of these cells to OXA. Further experiments showed that the mechanism by which RA enhanced the anticancer effects of OXA in CRC was by inhibiting the activation of the WNT/β-catenin signaling pathway. <b><i>Conclusions:</i></b> Because RA has been shown to be biocompatible in animal models, there is a possibility that RA could be developed as a sensitizer for resistant cancer cells or as a novel lead compound to enhance the therapeutic efficacy of OXA in resistant CRCs.</p>","PeriodicalId":55277,"journal":{"name":"Cancer Biotherapy and Radiopharmaceuticals","volume":" ","pages":"41-53"},"PeriodicalIF":2.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142711869","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":"<i>SERPINH1</i> as a Novel Biomarker for Colon Cancer Bone Metastasis with Machine Learning and Immunohistochemistry Validation.","authors":"Guoping Zhao, Tianjun Song, Qingfa Qing, Huaifu Cheng, Jinmin Zhao","doi":"10.1089/cbr.2024.0162","DOIUrl":"10.1089/cbr.2024.0162","url":null,"abstract":"<p><p><b><i>Background:</i></b> Bone metastasis (BM) is a serious clinical symptom of advanced colorectal cancer. However, there is a lack of effective biomarkers for early diagnosis and treatment. <b><i>Method:</i></b> RNA-seq data from public databases (GSE49355, GSE101607) were collected and normalized and batch effects were removed using the combat package. Differential expression analysis was performed to identify significant genes. Robust Rank Aggregation and machine learning algorithms were used to pinpoint candidate biomarkers. These biomarkers were validated using immunohistochemistry and further analyzed for survival rates. Enrichment analysis was conducted to explore biological mechanisms. Additionally, drug sensitivity and immune infiltration analyses were performed to provide insights into potential therapeutic targets. <b><i>Results:</i></b> Analysis results revealed 386 genes elevated in primary versus normal tissues and 26 genes varying between primary and BM. Serpin Protease Inhibitor Clade H1 (<i>SERPINH1)</i> as a novel biomarker for colon cancer metastasis. High <i>SERPINH1</i> expression correlates with poor survival outcomes and is linked to high lymphatic invasion and advanced cancer stages. Additionally, <i>SERPINH1</i> expression influences immune infiltration and is not predictive of chemotherapy response, but potential new drugs are suggested for high-expression cases. The gene also enriches classical cancer pathways such as Hedgehog and transforming growth factor-β. <b><i>Conclusions:</i></b> We identified novel colon cancer BM markers, including <i>SERPINH1</i>, using machine learning algorithms combined with traditional transcriptomic data and validated their expression through immunohistochemistry. This biomarker could significantly assist clinicians in making more precise treatment decisions.</p>","PeriodicalId":55277,"journal":{"name":"Cancer Biotherapy and Radiopharmaceuticals","volume":" ","pages":"31-40"},"PeriodicalIF":2.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142481429","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}
Qin Li, Bin Chen, Luz Angela Torres-de la Roche, Zimo Gong, Guilin Wang, Rui Zhuo, Rudy Leon De Wilde, Xiaopeng Chen, Wanwan Wang
{"title":"Ultrasound Genomics Reveals a Signature for Predicting Breast Cancer Prognosis and Therapy Response.","authors":"Qin Li, Bin Chen, Luz Angela Torres-de la Roche, Zimo Gong, Guilin Wang, Rui Zhuo, Rudy Leon De Wilde, Xiaopeng Chen, Wanwan Wang","doi":"10.1089/cbr.2024.0127","DOIUrl":"10.1089/cbr.2024.0127","url":null,"abstract":"<p><p><b><i>Background:</i></b> Breast cancer (BC) in women is the most common malignancy worldwide, but there is still a lack of validated tools to accurately assess patient prognosis and response to available chemotherapy treatment regimens. <b><i>Method:</i></b> We collected ultrasound images and transcriptome data of BC from our breast center and public database. Key ultrasound features were then identified by using the support vector machine (SVM) algorithm and correlated with prognostic genes. Long-term survival-related genes were identified through differential expression analysis, and a prognostic evaluation model was established by using Cox regression. In addition, <i>VPS28</i> from the model was identified as a promising biomarker for BC. <b><i>Results:</i></b> Using univariate logistic regression and SVM algorithms, we identified 12 ultrasound features significantly associated with chemotherapy response. Subsequent correlation and differential expression analyses linked 401 genes to these features, from which five key signature genes were derived using Lasso and multivariate Cox regression models. This signature not only facilitates the stratification of patients into risk-specific treatment pathways but also predicts their chemotherapy response, thus supporting personalized medicine in clinical settings. Notably, <i>VPS28</i>, in the signature, emerged as a significant biomarker, strongly associated with poor prognosis, greater tumor invasiveness, and differing expression across demographic groups. <b><i>Conclusion:</i></b> In this study, we use ultrasound genomics to reveal a signature that can provide an effective tool for prognostic assessment and predicting chemotherapy response in patients with BC.</p>","PeriodicalId":55277,"journal":{"name":"Cancer Biotherapy and Radiopharmaceuticals","volume":" ","pages":"54-61"},"PeriodicalIF":2.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142309181","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}
Yiping Xu, Yurong Cai, Youyuan Deng, Ye He, Juan Wu, Shunqiu Chang, Xuebo Yan, Jianguo Wang
{"title":"RAC2 as a Tumor-Suppressive Biomarker Associated with T Cell Infiltration in Breast Cancer.","authors":"Yiping Xu, Yurong Cai, Youyuan Deng, Ye He, Juan Wu, Shunqiu Chang, Xuebo Yan, Jianguo Wang","doi":"10.1089/cbr.2024.0142","DOIUrl":"10.1089/cbr.2024.0142","url":null,"abstract":"<p><p><b><i>Background:</i></b> RAC2 is critical in regulating the homeostasis of hematopoietic stem cells. Nonetheless, its role in breast cancer (BC) remains unclear, necessitating further investigation. <b><i>Methods:</i></b> The expression of RAC2 in BC and healthy tissues was acquired from The Cancer Genome Atlas. Its validity was further assessed using datasets from the gene expression omnibus database. The Tumor Immune Single-cell Hub database was used to collect and analyze the single-cell RNA sequencing datasets of BC. The diagnostic relevance of RAC2 was evaluated using receiver operating characteristic curves. Further assessment was carried out via enrichment analyses; Gene Set Analysis, immune scoring, single-cell sequencing, and immunohistochemical analysis were conducted to confirm the relationship between RAC2 expression and immune infiltration. <b><i>Results:</i></b> RAC2 expression was notably heightened in BC (<i>p</i> < 0.001). It was observed that a better prognosis was linked to heightened expression of RAC2 (<i>p</i> < 0.01), with the diagnostic efficacy of the marker noted to be good (area under the curve = 0.858). We found a lower percentage of protumor immune cells and a greater proportion of antitumor immune cells in the high RAC2. Our analysis revealed alterations in gene expression and an enriched network of immune pathways influenced by RAC2. Notably, cytotoxic genes, chemokines, chemokine receptors, immunostimulators, and immunosuppressive molecules positively correlated with RAC2 expression. RAC2 expression reliably predicted how patients would respond to two different therapeutic approaches in BC. <b><i>Conclusions:</i></b> The RAC2 was found to be a key biomarker in BC in the current study, demonstrating considerable potential as a prognostic and diagnostic marker. These results highlight the RAC2 potential to improve precision medicine strategies and treatment outcomes for patients with BC.</p>","PeriodicalId":55277,"journal":{"name":"Cancer Biotherapy and Radiopharmaceuticals","volume":" ","pages":"62-77"},"PeriodicalIF":2.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142549046","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}