Cancer Genetics最新文献

{"title":"In silico protein structural analysis of PRMT5 and RUVBL1 mutations arising in human cancers","authors":"Majd Al-Marrawi ,&nbsp;Ruben C. Petreaca ,&nbsp;Renee A. Bouley","doi":"10.1016/j.cancergen.2025.01.002","DOIUrl":"10.1016/j.cancergen.2025.01.002","url":null,"abstract":"<div><div>DNA double strand breaks (DSBs) can be generated spontaneously during DNA replication and are repaired primarily by Homologous Recombination (HR). However, efficient repair requires chromatin remodeling to allow the recombination machinery access to the break. <em>TIP60</em> is a complex conserved from yeast to humans that is required for histone acetylation and modulation of HR activity at DSBs. Two enzymatic activities within the <em>TIP60</em> complex, <em>KAT5</em> (a histone acetyltransferase) and <em>RUVBL1</em> (an AAA+ ATPase) are required for efficient HR repair. Post-translational modification of <em>RUVBL1</em> by the <em>PRMT5</em> methyltransferase activates the complex acetyltransferase activity and facilitates error free HR repair. In <em>S. pombe</em> a direct interaction between <em>PRMT5</em> and the acetyltransferase subunit of the <em>TIP60</em> complex (<em>KAT5</em>) was also identified. The <em>TIP60</em> complex has been partially solved experimentally in both humans and <em>S. cerevisiae</em>, but not <em>S. pombe</em>. Here, we used <em>in silico</em> protein structure analysis to investigate structural conservation between <em>S. pombe</em> and human <em>PRMT5</em> and <em>RUVBL1</em>. We found that there is more similarity in structure conservation between <em>S. pombe</em> and human proteins than between <em>S. cerevisiae</em> and human. Next, we queried the COSMIC database to analyze how mutations occurring in human cancers affect the structure and function of these proteins. Artificial intelligence algorithms that predict how likely mutations are to promote cellular transformation and immortalization show that <em>RUVBL1</em> mutations should have a more drastic effect than <em>PRMT5</em>. Indeed, <em>in silico</em> protein structural analysis shows that <em>PRMT5</em> mutations are less likely to destabilize enzyme function. Conversely, most <em>RUVBL1</em> mutations occur in a region required for interaction with its partner (<em>RUVBL2</em>). These data suggests that cancer mutations could destabilize the <em>TIP60</em> complex. Sequence conservation analysis between <em>S. pombe</em> and humans shows that the residues identified in cancer cells are highly conserved, suggesting that this may be an essential process in eukaryotic DSB repair. These results shed light on mechanisms of DSB repair and also highlight how <em>S. pombe</em> remains a great model system for analyzing DSB repair processes that are tractable in human cells.</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"292 ","pages":"Pages 49-56"},"PeriodicalIF":1.4,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143061280","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}

{"title":"Occult collision tumor of the gastroesophageal junction comprising adenocarcinomas with distinct molecular profiles","authors":"Maryjka B. Blaszczyk ,&nbsp;Sarag A. Boukhar ,&nbsp;Zhongren Zhou ,&nbsp;Lyudmyla Berim ,&nbsp;Shridar Ganesan ,&nbsp;Gregory M. Riedlinger","doi":"10.1016/j.cancergen.2025.01.001","DOIUrl":"10.1016/j.cancergen.2025.01.001","url":null,"abstract":"<div><div>Collision tumors, characterized by the coexistence of two unique neoplasms in close approximation, are rare and pose diagnostic challenges. This is particularly true when the unique neoplasms are of the same histologic type. Here we report such a case where comprehensive tumor profiling by next generation sequencing (NGS) as well as immunohistochemistry revealed two independent adenocarcinomas comprising what was initially diagnosed as a single adenocarcinoma of the gastroesophageal (GEJ) junction. Biopsy of the esophageal portion of the GEJ mass showed a mismatch repair deficient tumor with loss of immunoreactivity for MLH1 and PMS2, while the biopsy taken from the gastric portion of the mass revealed a separate tumor with a discordant, non-overlapping, set of molecular alterations, including an <em>EML4::ALK</em> fusion, as well as intact MMR. This case illustrates one way in which NGS can reveal diagnoses such as collision tumor that are wholly unexpected based on clinical and histological grounds. Such diagnoses can have important implications for patient care, particularly in cases where there is discordance for targetable molecular alterations.</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"292 ","pages":"Pages 27-34"},"PeriodicalIF":1.4,"publicationDate":"2025-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142979642","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}

{"title":"Omics approaches: Role in acute myeloid leukemia biomarker discovery and therapy","authors":"Fatemeh Sadat Shafiei ,&nbsp;Saeid Abroun ,&nbsp;Sadaf Vahdat ,&nbsp;Mohammad Rafiee","doi":"10.1016/j.cancergen.2024.12.006","DOIUrl":"10.1016/j.cancergen.2024.12.006","url":null,"abstract":"<div><div>Acute myeloid leukemia (AML) is the most common acute leukemia in adults and has the highest fatality rate. Patients aged 65 and above exhibit the poorest prognosis, with a mere 30 % survival rate within one year. One important issue in optimizing outcomes for AML patients is their limited ability to predict responses to specific therapies, response duration, and likelihood of relapse. Despite rigorous therapeutic interventions, a significant proportion of patients experience relapse. Consequently, there is a pressing need to introduce new targets for therapy. Sequencing and biotechnology have come a long way in the last ten years. This has made it easier for many omics technologies, like genomics, transcriptomics, proteomics, and metabolomics, to study molecular mechanisms of AML. An integrative approach is necessary to understand a complex biological process fully and offers an important opportunity to understand the information underlying diseases. In this review, we studied papers published between 2010 and 2024 employing omics approaches encompassing diagnosis, prognosis, and risk stratification of AML. Finally, we discuss prospects and challenges in applying -omics technologies to the discovery of novel biomarkers and therapy targets. Our review may be helpful for omics researchers who want to study AML from different molecular aspects.</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"292 ","pages":"Pages 14-26"},"PeriodicalIF":1.4,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142972981","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":"Genetic analysis uncovers potential mechanisms linking juvenile ldiopathic arthritisto breast cancer: A Bioinformatic Pilot study","authors":"Jianping Jiang ,&nbsp;Bolong Yin ,&nbsp;Xiangrong Luo ,&nbsp;Yan Chen ,&nbsp;Changyuan Wei","doi":"10.1016/j.cancergen.2024.09.004","DOIUrl":"10.1016/j.cancergen.2024.09.004","url":null,"abstract":"<div><h3>Background</h3><div>In recent years, concerns have emerged regarding the potential link between Juvenile idiopathic arthritis (JIA) and an elevated risk of developing breast cancer. However, the potential relationship between JIA and breast cancer is currently unclear. The objective of this study is to investigate the mechanism of JIA on cancer risk.</div></div><div><h3>Methods</h3><div>Use the Bulk-seq data related to JIA, selected from the GEO database, to explore potential candidate genes using methods such as WGCNA and consensus machine learning labeling. Verify using breast cancer Bulk-seq data from TCGA and scRNA-seq analyses.</div></div><div><h3>Results</h3><div>A total of 2050 genes potentially related to JIA were identified by WGCNA, and after merged with differentially expressed genes, 43 potential candidate genes were found. Subsequently, consensus machine learning label analysis was conducted on the aforementioned genes, and a total of 6 genes closely related to JIA were identified. In breast cancer, we found that PRRG4, NCR3 and CREB5 also had significant differences in TCGA. And it is closely related to prognosis. ScRNA-seq analysis showed that the expression of PRRG4 was different in T cells in JIA, and PRRG4 was mainly expressed in T cells in breast cancer.</div></div><div><h3>Conclusions</h3><div>The findings of this study support a mechanism between JIA and an increased risk of breast cancer.</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"290 ","pages":"Pages 51-55"},"PeriodicalIF":1.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142899740","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":"Analysis of nuclear receptor expression in head and neck cancer","authors":"Lindsey Mortensen ,&nbsp;Cynthia K. Koenigsberg ,&nbsp;Tyler G. Kimbrough ,&nbsp;Jesse Ping ,&nbsp;Gema Souto Adeva ,&nbsp;Beverly R. Wuertz ,&nbsp;Patrick Gaffney ,&nbsp;Frank G. Ondrey","doi":"10.1016/j.cancergen.2024.12.003","DOIUrl":"10.1016/j.cancergen.2024.12.003","url":null,"abstract":"<div><h3>Objective</h3><div>Studies of squamous cell carcinoma of the head and neck (HNSCC) have demonstrated the importance of nuclear receptors and their associated coregulators in the development and treatment of HNSCC. We sought to characterize members of the nuclear receptor super family through interrogation of RNA-Seq and microarray data.</div></div><div><h3>Materials and Methods</h3><div>TCGA RNA-Seq data within the cBioportal platform comparing HNSCC samples (<em>n</em> = 515 patients with RNA-Seq data) to normal tissue (<em>n</em> = 82 patients) was interrogated for significant differences in nuclear receptor expression. Affymetrix microarray analysis of HNSCC tumors relative to normal oral mucosa (41 tumor, 13 normal) was analyzed.</div></div><div><h3>Results</h3><div>Of the 48 NR genes and 19 NR cofactors examined, 99 % of tumor samples in the TCGA had some form of NR gene ‘alteration’ compared to normal tissue. These alterations predominantly encompass expression changes. NR genes (<em>PPARG</em>) and (<em>RORC</em>), and the NR cofactor, (<em>NCOA1</em>), were differentially expressed and downregulated in tumors compared to normal tissue.</div></div><div><h3>Conclusion</h3><div>We have discovered significant decreases in <em>PPARG</em> expression with co-occurring changes in genes involved with lipid metabolism and cell cycle progression in HNSCC. We are targeting PPARγ with thiazolidinediones in a series of clinical trials to restore normal signaling via differentiation to hopefully reverse carcinogenesis. We also observed several receptors with differential expression associated with clinical factors that may become the focus of interest in future targeting efforts. These data provide evidence for nuclear receptors playing a role in the dysregulation of gene expression in HNSCC and illustrate the utility of current bioinformatic tools for interrogating complex, high throughput data sets.</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"290 ","pages":"Pages 61-71"},"PeriodicalIF":1.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142928447","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":"Unraveling the Prognostic Role of t(1:19) in Pediatric Pre-B Acute Lymphoblastic Leukemia: Insights from a Saudi Nationwide Cohort","authors":"Ibrahim A. Sanduqji ,&nbsp;Walid Ballourah ,&nbsp;Suha Tashkandi ,&nbsp;Mohammed Essa ,&nbsp;Wasil Jastaniah ,&nbsp;Ibrahim Alghimlas ,&nbsp;Mohammed A. AlBalwi ,&nbsp;Mohammed Sahabi ,&nbsp;Abdullateef Mohammed Ahmed ,&nbsp;Naglla Elimam ,&nbsp;Dania A Monagel ,&nbsp;Ali Algiraigri","doi":"10.1016/j.cancergen.2024.10.003","DOIUrl":"10.1016/j.cancergen.2024.10.003","url":null,"abstract":"<div><div>Recurrent translocation t(1;19) (q23;p13) describes a unique cytogenetic group of childhood B-cell acute lymphoblastic leukemia (ALL). Historically, t(1;19)(q23;p13.3) has been associated with poor outcomes. However, recent data suggests that currently intensified treatments have overcome this dismal prognosis. We conducted this study to understand this type of translocation in our population. From January 1999 until May 2020, 44 children with t(1;19) were identified by cytogenetics analysis during charts review. Cytogenetics (CG) testing results (Karyotype and/or FISH) were retrieved from the medical files on 37/44 patients. Of the 37 patients with Cytogenetics results, a total of 12 patients were found to have t(1;19)(q23;p13.3) as the only detectable genetic change, 13 patients were presented with t(1;19)(q23;p13.3) plus further chromosomal rearrangement (Table 1), 12 patients were presented with a variation involving t(1;19)(q23;p13.3) with or without additional chromosomes rearrangement. Patients were treated on different protocols, yet most were derived from the North American guidelines. Among the included subjects, relapse or refractory disease was identified in 15 cases (34 %), and 12 died due to progressive refractory leukemia. At the five-year mark, the estimated overall survival rate stood at 72​​ %. No statistical difference existed between patients treated on the high-risk (HR) protocol and those treated on the standard-risk (SR) protocol. It appeared that t(1,19) standard risk ALL had more relapses on the standard risk protocol. Furthermore, Relapses were mostly earlier and poorly salvageable. As such, treatment intensification for standard risk ALL with t(1,19) is warranted.</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"290 ","pages":"Pages 1-5"},"PeriodicalIF":1.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142792599","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":"Machine learning analysis of CD4+ T cell gene expression in diverse diseases: insights from cancer, metabolic, respiratory, and digestive disorders","authors":"HuiPing Liao ,&nbsp;QingLan Ma ,&nbsp;Lei Chen ,&nbsp;Wei Guo ,&nbsp;KaiYan Feng ,&nbsp;YuSheng Bao ,&nbsp;Yu Zhang ,&nbsp;WenFeng Shen ,&nbsp;Tao Huang ,&nbsp;Yu-Dong Cai","doi":"10.1016/j.cancergen.2024.12.004","DOIUrl":"10.1016/j.cancergen.2024.12.004","url":null,"abstract":"<div><div>CD4⁺ T cells play a pivotal role in the immune system, particularly in adaptive immunity, by orchestrating and enhancing immune responses. CD4⁺ T cell-related immune responses exhibit diverse characteristics in different diseases. This study utilizes gene expression analysis of CD4⁺ T cells to classify and understand complex diseases. We analyzed the dataset consisting of samples from various diseases, including cancers, metabolic disorders, circulatory and respiratory diseases, and digestive ailments, as well as 53 healthy controls. Each sample contained expression data for 22,881 genes. Four feature ranking algorithms, incremental feature selection method, synthetic minority oversampling technique, and four classification algorithms were utilized to pinpoint essential genes, extract classification rules and build efficient classifiers. The following analysis focused on genes across rules, such as <em>AK4, CALU, LINC01271</em>, and <em>RUSC1-AS1. AK4</em> and <em>CALU</em> show fluctuating levels in diseases like asthma, Crohn's disease, and breast cancer. The analysis results and existing research suggest that they may play a role in these diseases. <em>LINC01271</em> generally has higher expression in conditions including asthma, Crohn's disease, and diabetes. <em>RUSC1-AS1</em> is more expressed in chronic diseases like asthma and Crohn's, but less in acute illnesses like tonsillitis and influenza. This highlights the distinct roles of these genes in different diseases. Our approach highlights the potential for developing novel therapeutic strategies based on the transcriptional profiles of CD4⁺ T cells.</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"290 ","pages":"Pages 56-60"},"PeriodicalIF":1.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142899742","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":"Screening and identification of gene expression in large cohorts of clinical tissue samples unveils the major involvement of EZH2 and SOX2 in lung cancer","authors":"Niharika ,&nbsp;Ankan Roy ,&nbsp;Ratan Sadhukhan ,&nbsp;Samir Kumar Patra","doi":"10.1016/j.cancergen.2024.11.006","DOIUrl":"10.1016/j.cancergen.2024.11.006","url":null,"abstract":"<div><div>Lung adenocarcinoma (LUAD), the primary subtype of Non-Small Cell Lung Cancer (NSCLC), accounts for 80 % to 85 % of cases. Due to suboptimal screening method, LUAD is often detected in late stage, leading to aggressive progression and poor outcomes. Therefore, early disease prognosis for the LUAD is high priority. In order to identify early detection biomarkers, we conducted a meta-analysis of mRNA expression TCGA and GTEx datasets from LUAD patients. A total of 795 differentially expressed genes (DEGs) were identified by exploring the Network-Analyst tool and utilizing combined effect size methods. DEGs refer to genes whose expression levels are significantly different (either higher or lower) compared to their normal baseline expression levels. KEGG pathway enrichment analysis highlighted the TNF signaling pathway as being prominently associated with these DEGs. Subsequently, using the MCODE and CytoHubba plugins in Cytoscape software, we filtered out the top 10 genes. Among these, SOX2 was the only gene exhibiting higher expression, while the others were downregulated. Consequently, our subsequent research focused on SOX2. Further transcription factor-gene network analysis revealed that enhancer of zeste homolog 2 (EZH2) is a significant partner of SOX2, potentially playing a crucial role in euchromatin-heterochromatin dynamics. Structure of SOX2 protein suggest that it is a non-druggable transcription factor, literature survey suggests the same. SOX2 is considered challenging to target directly, or \"non-druggable,\" because of several intrinsic properties that make it difficult to design effective therapeutic agents against it. The primary function of SOX2 is to bind DNA and regulates gene expression. Unlike enzymes or receptors with defined active sites or binding pockets, transcription factors typically have relatively flat or diffuse surfaces that do not offer obvious \"pockets\" for small molecules to bind effectively. Hence, we drove our focus to investigate on potential drug(s) targeting EZH2. Molecular docking analyses predicted most probable inhibitors of EZH2. We employed several predictive analysis tools and identified GSK343, as a promising inhibitor of EZH2.</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"290 ","pages":"Pages 16-35"},"PeriodicalIF":1.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142796365","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":"Genetic profile in primary tumor tissue of advanced lung adenocarcinoma patients with adrenal metastasis","authors":"Haiqiao Pan ,&nbsp;Hongbin Zhang ,&nbsp;Yongqian Zhang ,&nbsp;Xiaojing Chen ,&nbsp;Zhai Liu ,&nbsp;Yajing Wu ,&nbsp;Na Bai ,&nbsp;Yan Shi ,&nbsp;Min Zhao ,&nbsp;Lingling Zhu","doi":"10.1016/j.cancergen.2024.12.001","DOIUrl":"10.1016/j.cancergen.2024.12.001","url":null,"abstract":"<div><div>The aim of this study was to examine the genomic characteristics and explore the molecular mechanisms underlying adrenal metastases in lung adenocarcinoma. 57 patients diagnosed with lung adenocarcinoma (LUAD) and adrenal metastases (AM) were enrolled, alongside 33 controls diagnosed with non-adrenal metastases (non-AM) at the time of diagnosis. The primary lung cancer tissue sample were analyzed using next-generation sequencing. The molecular and clinical features were correlated with clinical outcomes. <em>TP53, EGFR</em> and <em>KRAS</em> were the most frequently mutated gene in both groups. <em>EGFR</em> mutations, especially rare variants (G724A, L747P, Q701 L, G719C, V769 L and S768I), exhibited significant enrichment in the non-AM group (<em>P</em>&lt;0.001). An elevated age-related signature in the group of patients with AM, whereas the non-AM group exhibited a higher BRCA signature. Potential prognostic biomarkers such as <em>KEAP1, LRP1B, NOTCH1</em> and <em>RET</em> mutations were detected in the non-AM group, while <em>ALK</em> mutations in the AM group correlated with shorter overall survival (<em>P</em>&lt;0.001). <em>KRAS</em> mutations in the early synchronous adrenal metastases group were also associated with shorter OS (<em>P</em>&lt;0.001). The analysis of 425 tumor genes in 29 patients with adrenal metastases showed significant enrichment in pathways associated with invasion and metastasis, including TNF signaling pathway and TGF-β signaling pathway. Patients without <em>EGFR</em> mutations in LUAD need to be more concerned about adrenal metastases. Meanwhile, patients with adrenal metastases harboring <em>ALK</em> or <em>KRAS</em> mutations have a poor prognosis and require more aggressive treatment. The TNF and TGF-β pathways might be associated with adrenal metastasis.</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"290 ","pages":"Pages 36-43"},"PeriodicalIF":1.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142824662","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}

{"title":"Diagnostic and prognostic potential of FBXO8 expression in kidney renal clear cell carcinoma and its regulation of renal adenocarcinoma cells","authors":"Zhouan Luo ,&nbsp;Xiaoping Wu ,&nbsp;Juanxia Xie ,&nbsp;Hao Tang ,&nbsp;Jingqi Chen ,&nbsp;Dongcai Ye ,&nbsp;Shangwen Dou ,&nbsp;Songning Chen","doi":"10.1016/j.cancergen.2024.11.004","DOIUrl":"10.1016/j.cancergen.2024.11.004","url":null,"abstract":"<div><h3>Background</h3><div>The F-box protein 8 Gene (<em>FBXO8</em>) has been shown to suppress invasion and metastasis in various cancer types. Recurrence and drug resistance pose significant challenges in renal cell carcinoma (RCC). Identifying novel biomarkers is crucial for addressing these issues.</div></div><div><h3>Methods</h3><div>Data on RNA sequencing and patient survival for KIRC was obtained from The Cancer Genome Atlas (TCGA), UALCAN, and Gene Expression Omnibus (GEO) databases. We confirmed <em>FBXO8</em> gene expression and its impact on survival. Clinical characteristics were classified, and <em>FBXO8</em> expression differences among various categories were observed. We conducted biofunctional predictions and analyzed the tumor microenvironment (TME), immune cell infiltration, and immune checkpoints in relation to <em>FBXO8</em> expression. FBXO8 was overexpressed using a plasmid, and we assessed Kidney renal clear cell carcinoma (KIRC) cell proliferation, migration, and apoptosis through CCK8, wound healing tests, and western blot analysis.</div></div><div><h3>Results</h3><div>Our findings revealed decreased <em>FBXO8</em> expression in KIRC, with patients exhibiting low <em>FBXO8</em> expression experiencing shorter survival times. The low expression group showed elevated TME immune and estimate scores. Biofunctional analyses indicated that <em>FBXO8</em> expression was notably linked to drug metabolism cytochrome P450, nutrition disease, receptor-ligand activity, and neuroactive ligand-receptor interaction. Furthermore, we discovered significant correlations between <em>FBXO8</em> expression and immune cell infiltration, as well as checkpoints such as <em>CD274</em>. Overexpression (OE) of FBXO8 led to a marked reduction in cell proliferation and migration, along with increased apoptosis, as evidenced by apoptosis-related protein expression.</div></div><div><h3>Conclusion</h3><div>This study demonstrates that <em>FBXO8</em> serves as a biomarker for KIRC and plays a role in regulating cell proliferation, migration, and apoptosis.</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"290 ","pages":"Pages 6-15"},"PeriodicalIF":1.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142796361","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}