Cancer Genetics最新文献

{"title":"PLAU serves as a prognostic biomarker correlated with perineural invasion in HNSCC","authors":"Haimeng Yin ,&nbsp;Zixiang Zhang ,&nbsp;Qing Zhang ,&nbsp;Yiwen You ,&nbsp;Zhenxin Zhang ,&nbsp;Yumo Han ,&nbsp;Qicheng Zhang ,&nbsp;Bo You","doi":"10.1016/j.cancergen.2025.04.008","DOIUrl":"10.1016/j.cancergen.2025.04.008","url":null,"abstract":"<div><div>In head and neck squamous cell carcinoma (HNSCC), perineural invasion (PNI) is a distinctive clinicopathologic feature associated with poor survival. To improve patient prognosis, our investigation delved into the underlying mechanism of PNI in HNSCC, especially laryngeal cancer and hypopharyngeal carcinoma. Based on data from the Cancer Genome Atlas (TCGA), genes were categorized into two groups based on the presence or absence of PNI. Plasminogen activator urokinase (PLAU) was screened out as the key molecular. Next, a tissue microarray comprising 68 patients with HNSCC was used to explore the association between PLAU and nerve growth factor (NGF), a positive control of PNI. Then, the co-culture model and cell damage function experiments were used to investigate the carcinogenic effect of PLAU. CCK8 and Transwell assays confirmed the role of PLAU in promoting proliferation and metastasis. The PC12 neurite growth assay and the co-culture system suggested that PLAU influences malignant behaviors by facilitating PNI. Moreover, introducing small molecule compounds to impede PLAU and NGF can effectively revert tumor progression in vivo. PLAU promotes tumor malignancy by facilitating PNI in HNSCC, offering a novel reference for clarifying the molecular mechanisms underlying PNI and identifying potential therapeutic targets for HNSCC.</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"294 ","pages":"Pages 145-155"},"PeriodicalIF":1.4,"publicationDate":"2025-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143902045","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":"Mechanistic study of Liquiritigenin inhibiting bladder cancer cell proliferation and migration by regulating STING1","authors":"Wuheng Li ,&nbsp;Qiang Yin ,&nbsp;Yihang Qiu ,&nbsp;Jiasheng Liu ,&nbsp;Jiaxin Wang ,&nbsp;Chengxi Li ,&nbsp;Dongchao Zhang ,&nbsp;Peng Zhang ,&nbsp;Haolong Lv ,&nbsp;Yue Lv ,&nbsp;Yongquan Wang","doi":"10.1016/j.cancergen.2025.04.007","DOIUrl":"10.1016/j.cancergen.2025.04.007","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;Bladder cancer (BLCA) is the most common malignant tumor in the urinary system, with a significantly higher incidence in men than in women, severely impacting quality of life. The STING1 gene (stimulator of interferon genes 1) plays a critical role in innate immunity by recognizing abnormal DNA and activating immune signaling pathways, promoting the expression of type I interferons and pro-inflammatory cytokines, thereby enhancing anti-tumor immune responses. Liquiritigenin (LQG), a flavonoid compound extracted from licorice, exhibits anti-inflammatory, antioxidant, and anti-cancer properties, capable of inhibiting tumor cell proliferation and invasion while regulating autophagy. This study aims to evaluate the role of LQG in regulating the STING1 gene and its anti-cancer mechanisms in bladder cancer.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;This study employed a multidimensional approach, combining bioinformatics analysis with both in vitro and in vivo experimental validation. Bioinformatics was utilized to assess the expression, function, and immune-related analyses of the STING1 gene. In vitro experiments included CCK-8 assays and colony formation assays to evaluate cell proliferation; Transwell migration assays and wound healing assays to assess migratory capacity; flow cytometry to analyze apoptosis; and immunofluorescence to observe the accumulation of autophagosomes. Additionally, molecular docking analysis was conducted to explore the interaction between LQG and the STING protein, while Western blotting was used to elucidate key molecular pathways. In vivo studies employed a mouse xenograft tumor model to systematically evaluate the anti-tumor effects and safety of LQG.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;The results showed that STING1 expression was significantly lower in bladder cancer tissues compared to normal tissues. Functional enrichment analysis indicated a close relationship between STING1 and immune response regulation. High STING1 expression was positively associated with different types of immune cells and important immune checkpoints. Analysis of immunotherapy indicated that high STING1 expression was associated with favorable clinical responses. Molecular docking confirmed that LQG directly targets the STING protein. Experimental results demonstrated that LQG inhibits tumor cell survival by targeting STING and blocking autophagic flux. Additionally, LQG downregulated the expression of MMP2 and MMP9, inhibiting migration and invasion, while enhancing apoptosis by modulating Bcl-2, Bax, and caspase-3 levels.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;div&gt;These findings underscore the critical role of STING1 in the immunobiology of bladder cancer, indicating its potential as a therapeutic target and biomarker for immunotherapy. The novel STING agonist LQG has multiple anti-tumor effects, including the modulation of apoptosis, inhibition of invasion, and enhancement of immune responses. This paves the way for ","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"294 ","pages":"Pages 156-170"},"PeriodicalIF":1.4,"publicationDate":"2025-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143924603","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":"Metformin regulates ferroptosis in Skin cutaneous melanoma via ATF3/NRF2 axis","authors":"Da Gu ,&nbsp;Yulin Sun ,&nbsp;Jianghui Wang ,&nbsp;Jinpeng Sun ,&nbsp;Huanmin Lou ,&nbsp;Weiting Kang","doi":"10.1016/j.cancergen.2025.04.006","DOIUrl":"10.1016/j.cancergen.2025.04.006","url":null,"abstract":"<div><h3>Background</h3><div>To explore the effects of metformin on the proliferation and ferroptosis of skin cutaneous melanoma (SKCM) and its potential molecular mechanisms, providing a new theoretical basis and strategy for the treatment of cutaneous melanoma.</div></div><div><h3>Methods</h3><div>The CCK-8 experiment was used to detect the effect of metformin on the proliferation of skin cutaneous melanoma cells. Kits were used to detect glutathione (GSH) content, reactive oxygen species (ROS), lipid peroxide (LPO), and malondialdehyde (MDA) levels to evaluate ferroptosis-related indicators. RNA-seq sequencing and related analyses were used to screen differentially expressed genes and explore their involved biological functions and signaling pathways. Western blot was used to detect the expression levels of ATF3 and NRF2 proteins and analyze the regulatory effect of metformin on the ATF3/NRF2 axis.</div></div><div><h3>Results</h3><div>Metformin significantly reduced the proliferation ability of skin cutaneous melanoma cells. The treated cells showed a decrease in GSH content and an accumulation of ROS, LPO, and MDA, suggesting that ferroptosis was regulated. RNA-seq analysis found 2068 differentially expressed genes, of which 897 were up-regulated and 1171 were down-regulated. The related pathways such as iron metabolism disorders and ferroptosis were activated. After metformin treatment, the expression of ATF3 mRNA in cells increased and was positively correlated with the concentration, while the expression in SKCM tissues decreased. At the same time, the expression of ATF3 protein increased and the expression of NRF2 protein decreased, suggesting that metformin may induce ferroptosis through the ATF3/NRF2 axis.</div></div><div><h3>Conclusion</h3><div>Metformin can induce ferroptosis by regulating ATF3/NRF2 axis, which may be a novel strategy for improving the treatment of skin cutaneous melanoma.</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"294 ","pages":"Pages 136-144"},"PeriodicalIF":1.4,"publicationDate":"2025-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143899265","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":"Rab5if is a potential therapeutic target of NSCLC","authors":"Linjuan Lu ,&nbsp;Lixiu Chen ,&nbsp;Feng Gao ,&nbsp;Chunming Xu ,&nbsp;Chen Ni ,&nbsp;Wenxia Qian","doi":"10.1016/j.cancergen.2025.04.005","DOIUrl":"10.1016/j.cancergen.2025.04.005","url":null,"abstract":"<div><h3>Purpose</h3><div>Due to disease progression and drug resistance, non-small cell lung cancer(NSCLC) mortality remains high, and the study of new targets that can inhibit tumor growth is very necessary. The purpose of this study was to investigate the role of Rab5if in the occurrence and development of NSCLC and explore its potential role in the treatment of NSCLC.</div></div><div><h3>Materials and Methods</h3><div>Rab5if overexpression and knockdown non-small cell lung cancer cell lines were constructed by lentivirus. Cellular assays were conducted to assess the impact of Rab5if on the functionality of lung cancer cells, The mechanism by which Rab5if influences the function of lung cancer cells was confirmed through Western blot analysis. The in vivo experiment was used to further verify the results of the in vitro experiment.</div></div><div><h3>Results</h3><div>Bioinformatics research found Rab5if mRNA increased in patients with NSCLC. Increased mRNA and protein levels of Rab5if were confirmed in local human NSCLC tissues. Knockdown of Rab5if in NSCLC cell lines by lentivirus significantly inhibited cell vigour, propagation and migration. In addition, mitochondrial function was impaired in lung cancer cells after Rab5if knockdown. In contrast, Rab5if overexpression promoted the proliferation and migration of NSCLC. Moreover, the impact Rab5if on the function of lung cancer cells was realized through the AKT-mTOR pathway. In the in vivo study, growth inhibition were observed in lung cancer xenografts transfected with Rab5if shRNA in nude mice. Similarly, xenografts of nude mice overexpressing Rab5if grew rapidly. The same pathway as in vitro was confirmed in vivo.</div></div><div><h3>Conclusion</h3><div>Rab5if is expected to be a novel therapeutic target for NSCLC.</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"294 ","pages":"Pages 123-135"},"PeriodicalIF":1.4,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143895797","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":"Clinicopathological correlation of PTPN3 expression in breast cancer and in silico drug screening against PTPN3 for therapeutics","authors":"Sanu Thankachan ,&nbsp;Boddapati Kalyani Bhardwaj ,&nbsp;Dimple Patel ,&nbsp;Kavitha KP ,&nbsp;Shama Prasada Kabekkodu ,&nbsp;Padmanaban S Suresh","doi":"10.1016/j.cancergen.2025.04.004","DOIUrl":"10.1016/j.cancergen.2025.04.004","url":null,"abstract":"<div><div>PTPN3 regulates cellular signaling and is dysregulated in cancer. There has been less research about the oncogenic impact of PTPN3 in breast cancer patients. This study analyzed PTPN3 mRNA levels and their prognostic significance in breast cancer using TCGA datasets. qRT-PCR was used to assess PTPN3 expression in formalin-fixed, paraffin-embedded Indian breast cancer patient samples (tumor-74, control-36). PTPN3 protein levels (ER-positive 15; ER-negative: 15; distant normal breast tissues: 20) were also immunohistochemically assessed using the H-score method. The biomarker potential was examined using a receiver operating characteristic (ROC) analysis. Docking and molecular dynamics (MD) simulations were used to find PTPN3 inhibitors (PDB ID: 2B49) from 892 FDA-approved natural chemicals in the ZINC database. PTPN3 mRNA and protein expression were significantly higher in breast cancers and associated with clinicopathological variables such as age, ER status, tumor stage, grade, Ki-67 index, menopause, and lymph node metastasis (<em>p</em> &lt; 0.05). ROC analysis revealed an AUC of 0.7654, indicating PTPN3′s biomarker potential. Docking yielded three high-affinity inhibitors: Cyclocort (ZINC000003977777), Toposar (ZINC000003938684), and Tetracycline (ZINC000084441937), with binding energies of -9.3, -8.73, and -8.66 kcal/mol, respectively. MD simulations confirmed stable connections via hydrogen bonds and hydrophobic interactions under minimal constraints. In conclusion, PTPN3 overexpression supports its role as a prognostic biomarker, and Cyclocort, Toposar, and Tetracycline need further confirmation as potential PTPN3 inhibitors.</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"294 ","pages":"Pages 111-122"},"PeriodicalIF":1.4,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143891790","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":"Ewing sarcoma of the rib with a rare PTEN mutation","authors":"Panagiota Fallon ,&nbsp;Anna Boulouta ,&nbsp;Constantina Papacharalambous ,&nbsp;Anastasios Kyriazoglou ,&nbsp;Panagiotis J. Vlachostergios","doi":"10.1016/j.cancergen.2025.04.003","DOIUrl":"10.1016/j.cancergen.2025.04.003","url":null,"abstract":"<div><h3>Background</h3><div>Rib involvement in Ewing sarcoma (ES) is very rare (3–5 %) and may often lead to unique presentations due to mass effect within the thorax. Molecular studies may sometimes offer insights into disease prognosis and possible targeted treatment approaches.</div></div><div><h3>Case Presentation</h3><div>Here we present the case of a 39-year-old female who presented with shortness of breath from a massive primary tumor in the right rib and lung. She was diagnosed with ES, which was confirmed by the presence of EWSR1/FLI-1 rearrangement and received multimodal therapy with neoadjuvant VDC-IE (vincristine-doxorubicin-cyclophosphamide, and ifosfamide-etoposide) followed by surgical excision after partial response, and adjuvant chemoradiation. Unfortunately, the patient experienced histologically confirmed local and distant recurrence after several months. NGS of the recurrent tumor revealed a pathogenic <em>PTEN</em> c.640C&gt;<em>T</em>(p.Q214*) nonsense variant with a very high variant allele frequency (VAF) of 82.6 % but negative germline assessment. She received several lines of chemotherapy but only demonstrated a short response to the oral multi-tyrosine kinase inhibitor cabozantinib before eventually passing away.</div></div><div><h3>Conclusions</h3><div><em>PTEN</em> mutations in ES, although rare, may result in a higher likelihood of chemotherapy resistance and poor prognosis. Clinical studies targeting specific molecular traits of these tumors, such as <em>PTEN</em> inactivation, could help improve outcomes in selected cases.</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"294 ","pages":"Pages 90-93"},"PeriodicalIF":1.4,"publicationDate":"2025-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143834079","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":"Regulator of G-protein signaling 14 (RGS14) promotes cancer growth in hepatocellular carcinoma","authors":"Yi Ran ,&nbsp;Liping Li ,&nbsp;Zhihua Wang ,&nbsp;Ting Sun ,&nbsp;Cong Wen ,&nbsp;Yixin Zhang ,&nbsp;Shu Wang ,&nbsp;Shishi Jiang ,&nbsp;Junjie Zheng ,&nbsp;Changjun Yin ,&nbsp;Chuankai Zhang","doi":"10.1016/j.cancergen.2025.04.002","DOIUrl":"10.1016/j.cancergen.2025.04.002","url":null,"abstract":"<div><h3>Background</h3><div>Hepatocellular carcinoma (HCC) is a major contributor to cancer-related deaths globally. The progression of HCC is influenced by a range of intrinsic and extrinsic factors, necessitating further research into the molecular mechanisms involved. While Regulator of G-protein Signaling 14 (RGS14) has shown emerging roles in cancer biology, its function in HCC remains poorly characterized.</div></div><div><h3>Materials and methods</h3><div>RGS14 expression and clinical significance were analyzed using TCGA-LIHC, HCCDB, and GEO datasets. Immunofluorescence (IF) staining was employed to validate protein expression. Functional assays, including cell proliferation, migration, invasion, and <em>in vivo</em> xenograft models, were conducted to assess the oncogenic role of RGS14. Bulk-mRNA sequencing was performed using <em>in situ</em> tumor tissues to identify RGS14-regulated pathways.</div></div><div><h3>Results</h3><div>RGS14 was significantly upregulated in HCC tissues and positively associated with poor patient outcomes. <em>In vitro</em> experiments demonstrated that RGS14 enhanced HCC cell proliferation, migration, and invasion, while <em>in vivo</em> studies confirmed its tumor-promoting effects. Mechanistically, RGS14 activated the extracellular matrix (ECM)-receptor interaction pathway to drive HCC progression.</div></div><div><h3>Conclusion</h3><div>Our findings suggest that RGS14 could serve as a novel prognostic marker and therapeutic target for HCC, contributing to improved treatment strategies.</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"294 ","pages":"Pages 80-89"},"PeriodicalIF":1.4,"publicationDate":"2025-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143834078","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":"Analytical validation of the Belay Vantage™ assay for evaluation of MGMT promoter methylation using enzymatically converted tumorDNA from cerebrospinal fluid","authors":"Kala F Schilter ,&nbsp;Qian Nie ,&nbsp;Jennifer N Adams,&nbsp;Rakshitha Jagadish,&nbsp;Anthony Acevedo,&nbsp;Alexandra Larson,&nbsp;Samantha A Vo,&nbsp;Brett A Domagala,&nbsp;Kyle M Hernandez,&nbsp;Christopher Douville,&nbsp;Yuxuan Wang,&nbsp;Brian Coe,&nbsp;Chetan Bettegowda,&nbsp;Honey V Reddi","doi":"10.1016/j.cancergen.2025.04.001","DOIUrl":"10.1016/j.cancergen.2025.04.001","url":null,"abstract":"<div><div><em>MGMT</em> promoter methylation status (hypermethylation) is one of the strongest prognostic and predictive biomarkers in glioblastoma (GBM) and is associated with a more favorable response to alkylating chemotherapies such as Temozolomide (TMZ). Additionally, it is associated with pseudo progression in GBM, a phenomenon in which early radiographic changes after treatment are indicative of possible tumor recurrence though on histological examination it is consistent with treatment effect. Current methods for evaluation of <em>MGMT</em> promoter methylation status are limited to tumor tissue, requiring invasive biopsy or surgery, prompting the need for a liquid biopsy-based assay to expand and manage therapeutic interventions. The Belay Vantage™ assay evaluates <em>MGMT</em> promoter methylation status in cerebrospinal fluid (CSF) of individuals with known or suspected central nervous system tumors using low input DNA. The assay uses quantitative polymerase chain reaction (qPCR) on DNA extracted from CSF after enzymatic conversion and has an analytical sensitivity of 95% and specificity of 100%.</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"294 ","pages":""},"PeriodicalIF":1.4,"publicationDate":"2025-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143839098","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":"Study on the correlation between BRCA1 gene polymorphism and hrHPV infection in cervical precancerous lesions","authors":"Dongling He ,&nbsp;Qing Lv ,&nbsp;Bin Li ,&nbsp;Min Xu ,&nbsp;Dewen Jiang ,&nbsp;Zhi Tang ,&nbsp;Yanjie Liu","doi":"10.1016/j.cancergen.2025.03.007","DOIUrl":"10.1016/j.cancergen.2025.03.007","url":null,"abstract":"<div><div>Cervical squamous intraepithelial lesions are precancerous lesions caused by high-risk subtypes of human papillomavirus (HPV). The development and prognosis of these lesions may be impacted by host genetics. Sanger sequencing was applied to sequence the breast cancer susceptibility gene (BRCA1) exons in exfoliated cervical cells. Fifteen single nucleotide polymorphisms (SNPs) were identified in the entire exon of BRCA1. It was found that there were 8 missense mutations, 1 nonsense mutation, 4 synonymous mutations, and 2 mutations not located in the protein-coding regions. Functional prediction of BRCA1 missense and synonymous mutation sites was performed using PolyPhen-2, ESEFinder3.0, and SIFT online software. The rs39812263 alteration in the BRCA1 gene was found to be significantly different by the sequencing. A significant difference was observed in the alterations of BRCA1 gene rs398122630 between hrHPV and thin- prep cytology test (TCT) groups (<em>p</em> &lt; 0.05), a negative correlation was observed with both hrHPV and TCT. The genotype and allele frequencies of the BRCA1 gene rs398122630 were significantly different from those of the control group (<em>p</em> &lt; 0.05). Rs398122630 may play a protective role in the progression of cervical cancer. This site is a nonsense mutation, which may lead to the premature termination of protein translation. Subsequently, we queried the Gene Expression Omnibus (GEO) and found that the expression of BRCA1 gene RNA gradually increased in cervical normal epithelium, high-grade cervical intraepithelial neoplasia (CIN), and cervical squamous cell carcinoma (CSCC).</div><div>Lentiviral vectors were used to construct stable cell lines with BRCA1 (breast cancer susceptibility gene 1) knockout and overexpression. The scratch healing rate of HeLa cells with BRCA1 knockout was significantly higher than that of the negative control group (<em>P</em> &lt; 0.05), while the difference in scratch healing rate in the overexpression group was not statistically significant. Compared to the control group, the proportion of cells in the G1 phase increased in the BRCA1 downregulated group (KD1), while the proportion of cells in the G1 phase decreased in the overexpression group (<em>P</em> &lt; 0.05). The percentage of cells in the S phase decreased in the downregulated group compared to the control group (<em>P</em> &lt; 0.05), and the proportion of cells in the G2 phase increased in the overexpression group compared to the control group (<em>P</em> &lt; 0.05), BRCA1 may be involved in the migration and cell cycle of HeLa cells.</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"294 ","pages":"Pages 99-110"},"PeriodicalIF":1.4,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143839099","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":"Immune prognostic model for glioblastoma based on the ssGSEA enrichment score","authors":"Takanari Okamoto ,&nbsp;Ryo Mizuta ,&nbsp;Ayako Demachi-Okamura ,&nbsp;Daisuke Muraoka ,&nbsp;Eiichi Sasaki ,&nbsp;Katsuhiro Masago ,&nbsp;Rui Yamaguchi ,&nbsp;Satoshi Teramukai ,&nbsp;Yoshihiro Otani ,&nbsp;Isao Date ,&nbsp;Shota Tanaka ,&nbsp;Yoshinobu Takahashi ,&nbsp;Naoya Hashimoto ,&nbsp;Hirokazu Matsushita","doi":"10.1016/j.cancergen.2025.03.005","DOIUrl":"10.1016/j.cancergen.2025.03.005","url":null,"abstract":"<div><h3>Purpose</h3><div>Few effective immune prognostic models based on the tumor immune microenvironment (TIME) for glioblastoma have been reported. Therefore, this study aimed to construct an immune prognostic model for glioblastoma by analyzing enriched biological processes and pathways in tumors.</div></div><div><h3>Methods</h3><div>A comprehensive single-sample gene set enrichment analysis (ssGSEA) of gene sets from the Molecular Signatures Database was performed using TCGA RNA sequencing data (141 glioblastoma cases). After evaluating gene sets associated with prognosis using univariable Cox regression, gene sets related to biological processes and tumor immunity in gliomas were extracted. Finally, the least absolute shrinkage and selection operator Cox regression refined the gene sets and a nomogram was constructed. The model was validated using CGGA (183 cases) and Aichi Cancer Center (42 cases) datasets.</div></div><div><h3>Results</h3><div>The immune prognostic model consisted of three gene sets related to biological processes (sphingolipids, steroid hormones, and intermediate filaments) and one related to tumor immunity (immunosuppressive chemokine pathways involving tumor-associated microglia and macrophages). Kaplan-Meier curves for the training (TCGA) and validation (CGGA) cohorts showed significantly worse overall survival in the high-risk group compared to the low-risk group (<em>p</em> &lt; 0.001 and <em>p</em> = 0.04, respectively). Furthermore, in silico cytometry revealed a significant increase in macrophages with immunosuppressive properties and T cells with effector functions in the high-risk group (<em>p</em> &lt; 0.01) across all cohorts.</div></div><div><h3>Conclusion</h3><div>Construction of an immune prognostic model based on the TIME assessment using ssGSEA could potentially provide valuable insights into the prognosis and immune profiles of patients with glioblastoma and guide treatment strategies.</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"294 ","pages":"Pages 32-41"},"PeriodicalIF":1.4,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143681123","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}