Cancer Genetics最新文献

英文中文

Immune prognostic model for glioblastoma based on the ssGSEA enrichment score

IF 1.4 4区医学 Q4 GENETICS & HEREDITY

Cancer Genetics

Pub Date : 2025-03-22 DOI: 10.1016/j.cancergen.2025.03.005

Takanari Okamoto , Ryo Mizuta , Ayako Demachi-Okamura , Daisuke Muraoka , Eiichi Sasaki , Katsuhiro Masago , Rui Yamaguchi , Satoshi Teramukai , Yoshihiro Otani , Isao Date , Shota Tanaka , Yoshinobu Takahashi , Naoya Hashimoto , Hirokazu Matsushita

Purpose

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.

Methods

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.

Results

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 (p < 0.001 and p = 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 (p < 0.01) across all cohorts.

Conclusion

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.

{"title":"Immune prognostic model for glioblastoma based on the ssGSEA enrichment score","authors":"Takanari Okamoto , Ryo Mizuta , Ayako Demachi-Okamura , Daisuke Muraoka , Eiichi Sasaki , Katsuhiro Masago , Rui Yamaguchi , Satoshi Teramukai , Yoshihiro Otani , Isao Date , Shota Tanaka , Yoshinobu Takahashi , Naoya Hashimoto , 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> < 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> < 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}

引用次数: 0

Mutation status in yes-associated protein 1 (YAP1) in an insulinoma cell line Rin-5F

IF 1.4 4区医学 Q4 GENETICS & HEREDITY

Cancer Genetics

Pub Date : 2025-03-20 DOI: 10.1016/j.cancergen.2025.03.006

Takayoshi Kiba

Previous research indicates that YAP1 mutations may enhance responses to immune checkpoint inhibitors, and this mutation could serve as a novel predictor of response to immunotherapy across various cancers by increasing mutation counts. The insulin-secreting pancreatic cell line Rin-5F is commonly used in pharmacological and toxicological studies. In the present study, the author has examined mutations in the YAP1 gene using genomic DNA and complementary DNA from Rin-5F cells. No mutations in the YAP1 gene were identified in the current investigation. The status of the YAP1 gene in an insulinoma cell line has not been previously documented. According to previous research, YAP1 mutations may be associated with enhanced responses to immune checkpoint inhibitors. Given that there is no mutation of the YAP1 gene in this insulinoma cell line, it is possible that immune checkpoint inhibitors may have a reduced impact on insulinoma. To address this question, further clinical trials of immune checkpoint inhibitors are needed for neuroendocrine tumors, such as insulinomas.

引用次数: 0

Identification of new immune target and signaling for cancer immunotherapy

IF 1.4 4区医学 Q4 GENETICS & HEREDITY

Cancer Genetics

Pub Date : 2025-03-20 DOI: 10.1016/j.cancergen.2025.03.004

Sakshi Narote, Sharav A. Desai, Vipul P. Patel, Rutuja Deshmukh, Nikita Raut, Sejal Dapse

Immunotherapy has become one of the innovative treatments in malignancy as it activates the immune system to find and eliminate malignant cells. The tumor immunology interface has become increasingly intricate, making the identification of new immune targets and signalling pathways on which to base improved therapeutic strategies an ongoing process. This review, we goal to clarify the contacts between cancer and immune system with a focus on immune surveillance as well as immune evasion mechanisms. Comprehensive immunotherapeutic therapies are overviewed with ICI (CTLA-4, PD-1, PD-L1), CAR-T cell therapy, and cancer vaccines whereas, advanced therapies targeting new immune checkpoints are also elucidated including TIM-3, LAG-3, and TIGIT. The JAK/STAT, MAPK and PI3K-AKT-mTOR pathways are reviewed with regards to cancer progression and immunotherapeutic resistance. The dysregulation of these pathways gives hope for the identification of fresh targets for therapy. Genomics, proteomics, immunopeptidomics, single cell mass spectrometry, CRISPR-based functional genomics and bioinformatics are described as essential for immune target identification and for mapping of cancer relevant signaling pathways. This review also considers some emerging issues in the subject area like the tumor heterogeneity, immune-related adverse events (irAEs), and personalized treatment. These barriers are described to facilitate the understanding of ways to overcome them and increase the efficacy of immunotherapies through combination therapies. This means that by developing new knowledge of immunological targets and pathways, immunoprecision medicine for cancer could greatly enhance outcomes.

{"title":"Identification of new immune target and signaling for cancer immunotherapy","authors":"Sakshi Narote, Sharav A. Desai, Vipul P. Patel, Rutuja Deshmukh, Nikita Raut, Sejal Dapse","doi":"10.1016/j.cancergen.2025.03.004","DOIUrl":"10.1016/j.cancergen.2025.03.004","url":null,"abstract":"<div><div>Immunotherapy has become one of the innovative treatments in malignancy as it activates the immune system to find and eliminate malignant cells. The tumor immunology interface has become increasingly intricate, making the identification of new immune targets and signalling pathways on which to base improved therapeutic strategies an ongoing process. This review, we goal to clarify the contacts between cancer and immune system with a focus on immune surveillance as well as immune evasion mechanisms. Comprehensive immunotherapeutic therapies are overviewed with ICI (CTLA-4, PD-1, PD-L1), CAR-T cell therapy, and cancer vaccines whereas, advanced therapies targeting new immune checkpoints are also elucidated including TIM-3, LAG-3, and TIGIT. The JAK/STAT, MAPK and PI3K-AKT-mTOR pathways are reviewed with regards to cancer progression and immunotherapeutic resistance. The dysregulation of these pathways gives hope for the identification of fresh targets for therapy. Genomics, proteomics, immunopeptidomics, single cell mass spectrometry, CRISPR-based functional genomics and bioinformatics are described as essential for immune target identification and for mapping of cancer relevant signaling pathways. This review also considers some emerging issues in the subject area like the tumor heterogeneity, immune-related adverse events (irAEs), and personalized treatment. These barriers are described to facilitate the understanding of ways to overcome them and increase the efficacy of immunotherapies through combination therapies. This means that by developing new knowledge of immunological targets and pathways, immunoprecision medicine for cancer could greatly enhance outcomes.</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"294 ","pages":"Pages 57-75"},"PeriodicalIF":1.4,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143704634","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Genetic testing referral and germline pathogenic variants in patients with breast cancer and another non-breast cancer

IF 1.4 4区医学 Q4 GENETICS & HEREDITY

Cancer Genetics

Pub Date : 2025-03-18 DOI: 10.1016/j.cancergen.2025.03.003

Rachel Hodan , Victor Ritter , Summer Han , Shilpa Narayan , Mina Satoyoshi , Allison W. Kurian

Background

Guidelines recommend germline genetic testing for specific combinations of primary cancers and ages of diagnoses, but do not recommend testing for all patients with multiple primary cancers (MPC). Patients with breast cancer are more likely to receive genetic testing. Here, we evaluated whether a first breast cancer was more likely than another first cancer type to prompt testing referral.

Methods

Using Oncoshare, a breast cancer research database of medical records and the California Cancer Registry, we identified female patients with MPC diagnosed January 2000-June 2023 with breast cancer as either the first or second cancer and seen at Stanford Health Care. We analyzed genetic testing rates after first versus second cancer diagnosis and the yield of pathogenic variants (PV). We evaluated the association between the receipt of genetic testing and timing of breast cancer (1st or 2nd), using univariate and multivariable logistic regression adjusted for age at first diagnosis, race/ethnicity, and time between first and second diagnoses.

Results

1,069 patients met eligibility criteria; 75 % were non-Hispanic white, and 73 % had breast as the first cancer. 342 (32 %) patients had testing, of which 113 (33 %) had at least one PV. Patients with first breast cancer had a trend toward higher testing rate, (OR 1.62, 95 % CI 0.9–3.0), p = 0.11.

Conclusion

Using a breast cancer research database, MPC patients showed a trend toward being more likely to receive genetic testing when breast cancer preceded another cancer. High yield for a germline pathogenic variant suggests that all MPC patients should have cancer genetics risk assessment.

{"title":"Genetic testing referral and germline pathogenic variants in patients with breast cancer and another non-breast cancer","authors":"Rachel Hodan , Victor Ritter , Summer Han , Shilpa Narayan , Mina Satoyoshi , Allison W. Kurian","doi":"10.1016/j.cancergen.2025.03.003","DOIUrl":"10.1016/j.cancergen.2025.03.003","url":null,"abstract":"<div><h3>Background</h3><div>Guidelines recommend germline genetic testing for specific combinations of primary cancers and ages of diagnoses, but do not recommend testing for all patients with multiple primary cancers (MPC). Patients with breast cancer are more likely to receive genetic testing. Here, we evaluated whether a first breast cancer was more likely than another first cancer type to prompt testing referral.</div></div><div><h3>Methods</h3><div>Using Oncoshare, a breast cancer research database of medical records and the California Cancer Registry, we identified female patients with MPC diagnosed January 2000-June 2023 with breast cancer as either the first or second cancer and seen at Stanford Health Care. We analyzed genetic testing rates after first versus second cancer diagnosis and the yield of pathogenic variants (PV). We evaluated the association between the receipt of genetic testing and timing of breast cancer (1st or 2nd), using univariate and multivariable logistic regression adjusted for age at first diagnosis, race/ethnicity, and time between first and second diagnoses.</div></div><div><h3>Results</h3><div>1,069 patients met eligibility criteria; 75 % were non-Hispanic white, and 73 % had breast as the first cancer. 342 (32 %) patients had testing, of which 113 (33 %) had at least one PV. Patients with first breast cancer had a trend toward higher testing rate, (OR 1.62, 95 % CI 0.9–3.0), <em>p</em> = 0.11.</div></div><div><h3>Conclusion</h3><div>Using a breast cancer research database, MPC patients showed a trend toward being more likely to receive genetic testing when breast cancer preceded another cancer. High yield for a germline pathogenic variant suggests that all MPC patients should have cancer genetics risk assessment.</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"294 ","pages":"Pages 42-46"},"PeriodicalIF":1.4,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143681124","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

HSP110 T17 marker matches the pentaplex panel and outperforms CAT-25 for detecting microsatellite instability in sporadic colorectal cancer

IF 1.4 4区医学 Q4 GENETICS & HEREDITY

Cancer Genetics

Pub Date : 2025-03-06 DOI: 10.1016/j.cancergen.2025.03.002

Nasreddine Rajoua , Antoine Daunay , Wissem Triki , Oussema Baraket , Sami Bouchoucha , Houcine Maghrebi , Aymen Mabrouk , Jean-François Deleuze , Alexandre How-Kit , Maher Kharrat

Microsatellite instability (MSI) is an important biomarker in colorectal cancer (CRC), influencing prognosis and treatment decisions. While conventional MSI detection typically relies on the pentaplex panel, newer markers like HSP110 T17 (HT-17) and CAT-25 may offer simpler, more cost-effective alternatives. This study aimed to assess the effectiveness of HT-17 and CAT-25 for detecting MSI in sporadic CRC and to explore any links between MSI status and clinicopathological features. A total of 96 Tunisian sporadic CRC patients were included, with MSI status evaluated using HT-17, CAT-25, and the refined mononucleotide repeat pentaplex panel through microsatellite genotyping. Clinicopathological data, such as tumor location and age at diagnosis, were also analyzed for associations with MSI. Among the 96 patients, 9 (9.38%) showed MSI, while 87 were microsatellite stable (MSS). HT-17 demonstrated 100% accuracy and sensitivity, matching the pentaplex panel's performance, while CAT-25 showed limited detection ability. MSI status was significantly linked to tumors in the proximal colon and, unexpectedly, to younger patients (<50 years old). HT-17 proved to be a reliable MSI marker in CRC, offering equivalent performance to the pentaplex panel, with the added advantages of simplicity and cost efficiency. The associations between MSI, tumor location, and younger age at diagnosis may provide valuable insights into CRC biology and clinical management. Further studies with larger cohorts are needed to validate HT-17′ s clinical potential, with the goal of improving personalized treatment strategies and prognostic accuracy for CRC patients.

{"title":"HSP110 T17 marker matches the pentaplex panel and outperforms CAT-25 for detecting microsatellite instability in sporadic colorectal cancer","authors":"Nasreddine Rajoua , Antoine Daunay , Wissem Triki , Oussema Baraket , Sami Bouchoucha , Houcine Maghrebi , Aymen Mabrouk , Jean-François Deleuze , Alexandre How-Kit , Maher Kharrat","doi":"10.1016/j.cancergen.2025.03.002","DOIUrl":"10.1016/j.cancergen.2025.03.002","url":null,"abstract":"<div><div>Microsatellite instability (MSI) is an important biomarker in colorectal cancer (CRC), influencing prognosis and treatment decisions. While conventional MSI detection typically relies on the pentaplex panel, newer markers like HSP110 T17 (HT-17) and CAT-25 may offer simpler, more cost-effective alternatives. This study aimed to assess the effectiveness of HT-17 and CAT-25 for detecting MSI in sporadic CRC and to explore any links between MSI status and clinicopathological features. A total of 96 Tunisian sporadic CRC patients were included, with MSI status evaluated using HT-17, CAT-25, and the refined mononucleotide repeat pentaplex panel through microsatellite genotyping. Clinicopathological data, such as tumor location and age at diagnosis, were also analyzed for associations with MSI. Among the 96 patients, 9 (9.38%) showed MSI, while 87 were microsatellite stable (MSS). HT-17 demonstrated 100% accuracy and sensitivity, matching the pentaplex panel's performance, while CAT-25 showed limited detection ability. MSI status was significantly linked to tumors in the proximal colon and, unexpectedly, to younger patients (<50 years old). HT-17 proved to be a reliable MSI marker in CRC, offering equivalent performance to the pentaplex panel, with the added advantages of simplicity and cost efficiency. The associations between MSI, tumor location, and younger age at diagnosis may provide valuable insights into CRC biology and clinical management. Further studies with larger cohorts are needed to validate HT-17′ s clinical potential, with the goal of improving personalized treatment strategies and prognostic accuracy for CRC patients.</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"294 ","pages":"Pages 21-26"},"PeriodicalIF":1.4,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143580291","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Biological landscape of human papilloma virus-related head and neck cancer according to virus genotype

IF 1.4 4区医学 Q4 GENETICS & HEREDITY

Cancer Genetics

Pub Date : 2025-03-05 DOI: 10.1016/j.cancergen.2025.02.010

Katsuhiro Masago , Hiromasa Ishihara , Hiroaki Kuroda , Eiichi Sasaki , Yasuko Fujita , Shiro Fujita , Yoshitsugu Horio , Michi Sawabe , Shintaro Beppu , Daisuke Nishikawa , Hoshino Terada , Toshihiro Kishikawa , Hidenori Suzuki , Hirofumi Shibata , Takenori Ogawa , Nobuhiro Hanai , Hirokazu Matsushita

Human papillomavirus (HPV), particularly strains 16 and 18, contributes to oropharyngeal squamous cell carcinoma (OPSCC), even in non-smokers and non-drinkers. This study investigated gene expression variations in HPV-positive OPSCCs according to the virus genotype. An RNA sequencing analysis of 36 p16-positive OPSCC patients revealed distinct expression patterns between tumors with only E6/E7 transcripts (E6E7) and those with additional E5 transcripts (E5-added). The E6E7 group displayed activation of FOS-related pathways and the NF-κB signaling pathway. Notably, the genes associated with tumor growth and cancer antigens differed between the groups. These findings suggest that the presence of HPV E5 might influence the transformation stages and gene expression, potentially affecting patient outcomes. The E5-added group expressed multiple cancer-associated antigens, presenting potential targets for personalized immunotherapy approaches for HPV-positive OPSCC.

{"title":"Biological landscape of human papilloma virus-related head and neck cancer according to virus genotype","authors":"Katsuhiro Masago , Hiromasa Ishihara , Hiroaki Kuroda , Eiichi Sasaki , Yasuko Fujita , Shiro Fujita , Yoshitsugu Horio , Michi Sawabe , Shintaro Beppu , Daisuke Nishikawa , Hoshino Terada , Toshihiro Kishikawa , Hidenori Suzuki , Hirofumi Shibata , Takenori Ogawa , Nobuhiro Hanai , Hirokazu Matsushita","doi":"10.1016/j.cancergen.2025.02.010","DOIUrl":"10.1016/j.cancergen.2025.02.010","url":null,"abstract":"<div><div>Human papillomavirus (HPV), particularly strains 16 and 18, contributes to oropharyngeal squamous cell carcinoma (OPSCC), even in non-smokers and non-drinkers. This study investigated gene expression variations in HPV-positive OPSCCs according to the virus genotype. An RNA sequencing analysis of 36 p16-positive OPSCC patients revealed distinct expression patterns between tumors with only E6/E7 transcripts (E6E7) and those with additional E5 transcripts (E5-added). The E6E7 group displayed activation of FOS-related pathways and the NF-κB signaling pathway. Notably, the genes associated with tumor growth and cancer antigens differed between the groups. These findings suggest that the presence of HPV E5 might influence the transformation stages and gene expression, potentially affecting patient outcomes. The E5-added group expressed multiple cancer-associated antigens, presenting potential targets for personalized immunotherapy approaches for HPV-positive OPSCC.</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"294 ","pages":"Pages 27-31"},"PeriodicalIF":1.4,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143580190","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

ENPP1 promotes immune suppression, drug resistance, and adverse outcomes in bladder cancer: Potential for targeted therapy

IF 1.4 4区医学 Q4 GENETICS & HEREDITY

Cancer Genetics

Pub Date : 2025-03-04 DOI: 10.1016/j.cancergen.2025.03.001

Chengyu You , Qixiang Fang , Xi Xiao , Yang Liu , Weiguang Yang , Liangliang Qing , Qingchao Li , Rongxin Li , Yanan Wang , Zhilong Dong

Background

ENPP1 (Ectonucleotide Pyrophosphatase/Phosphodiesterase 1) plays a critical role in multiple cancers; however, its role in bladder cancer (BC) remains largely unexplored. This study investigates the impact of ENPP1 on tumor progression, apoptosis, and the immune microenvironment through bioinformatics and experimental validation.

Materials and methods

ENPP1 expression and clinical significance were analyzed using TCGA-BLCA, GEO datasets, and a local clinical cohort of 36 BC patients. Immune infiltration and functional enrichment were assessed using ESTIMATE, CIBERSORT, and clusterProfiler. Single-cell RNA sequencing (scRNA-seq) data examined ENPP1 expression in BC tissues. Stable ENPP1-overexpressing (UMUC3) and ENPP1-knockdown (J82) cell lines were established. Functional assays, including proliferation, migration, and apoptosis marker analysis, were performed.

Results

RT-qPCR, Western blotting, and immunohistochemistry confirmed differential ENPP1 expression between BC tissues and adjacent normal tissues. High ENPP1 expression was associated with worse overall survival (OS), advanced T and N stages, and poor pathological grades. Functional assays demonstrated that ENPP1 overexpression enhanced proliferation, migration, and apoptosis resistance, while knockdown suppressed these processes. Mechanistically, ENPP1 overexpression reduced pro-apoptotic markers BAX and Caspase-3 while increasing anti-apoptotic Bcl-2. Immune infiltration analysis revealed a positive correlation between ENPP1 expression and M2 macrophage infiltration, alongside decreased CD8+ T cell infiltration. scRNA-seq identified high ENPP1 expression in cancer-associated fibroblasts and epithelial cells. Drug sensitivity analysis linked elevated ENPP1 expression to resistance against chemotherapies like gemcitabine and cytarabine.

Conclusion

ENPP1 drives tumor progression, modulates immune infiltration, and contributes to chemotherapy resistance in BC, underscoring its potential as a therapeutic target.

{"title":"ENPP1 promotes immune suppression, drug resistance, and adverse outcomes in bladder cancer: Potential for targeted therapy","authors":"Chengyu You , Qixiang Fang , Xi Xiao , Yang Liu , Weiguang Yang , Liangliang Qing , Qingchao Li , Rongxin Li , Yanan Wang , Zhilong Dong","doi":"10.1016/j.cancergen.2025.03.001","DOIUrl":"10.1016/j.cancergen.2025.03.001","url":null,"abstract":"<div><h3>Background</h3><div>ENPP1 (Ectonucleotide Pyrophosphatase/Phosphodiesterase 1) plays a critical role in multiple cancers; however, its role in bladder cancer (BC) remains largely unexplored. This study investigates the impact of ENPP1 on tumor progression, apoptosis, and the immune microenvironment through bioinformatics and experimental validation.</div></div><div><h3>Materials and methods</h3><div>ENPP1 expression and clinical significance were analyzed using TCGA-BLCA, GEO datasets, and a local clinical cohort of 36 BC patients. Immune infiltration and functional enrichment were assessed using ESTIMATE, CIBERSORT, and clusterProfiler. Single-cell RNA sequencing (scRNA-seq) data examined ENPP1 expression in BC tissues. Stable ENPP1-overexpressing (UMUC3) and ENPP1-knockdown (J82) cell lines were established. Functional assays, including proliferation, migration, and apoptosis marker analysis, were performed.</div></div><div><h3>Results</h3><div>RT-qPCR, Western blotting, and immunohistochemistry confirmed differential ENPP1 expression between BC tissues and adjacent normal tissues. High ENPP1 expression was associated with worse overall survival (OS), advanced T and N stages, and poor pathological grades. Functional assays demonstrated that ENPP1 overexpression enhanced proliferation, migration, and apoptosis resistance, while knockdown suppressed these processes. Mechanistically, ENPP1 overexpression reduced pro-apoptotic markers BAX and Caspase-3 while increasing anti-apoptotic Bcl-2. Immune infiltration analysis revealed a positive correlation between ENPP1 expression and M2 macrophage infiltration, alongside decreased CD8+ <em>T</em> cell infiltration. scRNA-seq identified high ENPP1 expression in cancer-associated fibroblasts and epithelial cells. Drug sensitivity analysis linked elevated ENPP1 expression to resistance against chemotherapies like gemcitabine and cytarabine.</div></div><div><h3>Conclusion</h3><div>ENPP1 drives tumor progression, modulates immune infiltration, and contributes to chemotherapy resistance in BC, underscoring its potential as a therapeutic target.</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"294 ","pages":"Pages 1-14"},"PeriodicalIF":1.4,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143580189","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Composite mantle cell lymphoma with cryptic ins(11;2)(q13;p11.2p11.2)/IGK::CCND1 and lymphoplasmacytic lymphoma with MYD88 L265P mutation

IF 1.4 4区医学 Q4 GENETICS & HEREDITY

Cancer Genetics

Pub Date : 2025-03-04 DOI: 10.1016/j.cancergen.2025.02.012

Fumiyo Maekawa , Masahiko Hayashida , Kayo Takeoka , Yoshinari Chagi , Riku Takahashi , Chiyuki Kishimori , Shinichi Kotani , Takashi Akasaka , Shinichi Sakamoto , Shinji Sumiyoshi , Hitoshi Ohno

A woman in her 80 s presented with generalized lymphadenopathy, bone marrow (BM) involvement, and leukemic manifestation. Lymph node biopsy revealed typical histopathology of mantle cell lymphoma (MCL) and the CD5⁺ and immunoglobulin μ⁺δ⁺/λ⁺ immunophenotype, with unmutated IGHV. BM was infiltrated with not only MCL but also another B-cell tumor that was CD5⁻ and μ^bright+δ⁺/κ⁺, being consistent with M proteins in the serum and urine, with mutated IGHV. As the latter lymphoma component carried the MYD88 L265P mutation, this case represented a composite of MCL and lymphoplasmacytic lymphoma. Next-generation sequencing revealed a cryptic insertion of IGK enhancer sequences into the CCND1-major translocation cluster, accounting for CCND1 expression in MCL cells recognized by immunohistochemistry. Composite lymphoma is rare, but a correct diagnosis is required because effective treatments for each component are now available.

{"title":"Composite mantle cell lymphoma with cryptic ins(11;2)(q13;p11.2p11.2)/IGK::CCND1 and lymphoplasmacytic lymphoma with MYD88 L265P mutation","authors":"Fumiyo Maekawa , Masahiko Hayashida , Kayo Takeoka , Yoshinari Chagi , Riku Takahashi , Chiyuki Kishimori , Shinichi Kotani , Takashi Akasaka , Shinichi Sakamoto , Shinji Sumiyoshi , Hitoshi Ohno","doi":"10.1016/j.cancergen.2025.02.012","DOIUrl":"10.1016/j.cancergen.2025.02.012","url":null,"abstract":"<div><div>A woman in her 80 s presented with generalized lymphadenopathy, bone marrow (BM) involvement, and leukemic manifestation. Lymph node biopsy revealed typical histopathology of mantle cell lymphoma (MCL) and the CD5<sup>+</sup> and immunoglobulin μ<sup>+</sup>δ<sup>+</sup>/λ<sup>+</sup> immunophenotype, with unmutated <em>IGHV</em>. BM was infiltrated with not only MCL but also another B-cell tumor that was CD5<sup>−</sup> and μ<sup>bright+</sup>δ<sup>+</sup>/κ<sup>+</sup>, being consistent with M proteins in the serum and urine, with mutated <em>IGHV</em>. As the latter lymphoma component carried the <em>MYD88</em> L265P mutation, this case represented a composite of MCL and lymphoplasmacytic lymphoma. Next-generation sequencing revealed a cryptic insertion of <em>IGK</em> enhancer sequences into the <em>CCND1</em>-major translocation cluster, accounting for CCND1 expression in MCL cells recognized by immunohistochemistry. Composite lymphoma is rare, but a correct diagnosis is required because effective treatments for each component are now available.</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"294 ","pages":"Pages 15-20"},"PeriodicalIF":1.4,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143580290","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

RECQL4-related Rothmund-Thomson syndrome: A case series and literature review

IF 1.4 4区医学 Q4 GENETICS & HEREDITY

Cancer Genetics

Pub Date : 2025-02-26 DOI: 10.1016/j.cancergen.2025.02.013

Stephanie Ka Lun Ho , Grace Pui Yung Tong , Lai-Ting Leung , Shirley Sze Wing Cheng , Eric Chun Ho Fu , Ivan Fai Man Lo , Anthony Pak Yin Liu , Ho-ming Luk

Rothmund-Thomson syndrome (RTS) is a multisystemic tumour-predisposing genodermatosis caused by biallelic pathogenic alterations in the ANAPC1 gene or RECQL4 gene. Herein we describe the clinical and genetic findings in three individuals with molecularly substantiated RECQL4-related RTS. Based on the disease course of two patients with osteosarcoma, we highlight the critical importance of early diagnosis.

引用次数: 0

Ultra-sensitive detection of melanoma NRAS mutant ctDNA based on programmable endonucleases

IF 1.4 4区医学 Q4 GENETICS & HEREDITY

Cancer Genetics

Pub Date : 2025-02-26 DOI: 10.1016/j.cancergen.2025.02.008

Zuoying Zhang , Qing Ji , Zhanfang Zhang , Bao Lyu , Pei Li , Liyi Zhang , Kaifei Chen , Meiyu Fang , Jinzhao Song

Background

Melanoma is a complex and often fatal disease, with NRAS being one of the most frequently mutated genes in this type of cancer. Liquid biopsies, specifically tests for circulating tumor DNA (ctDNA), represent a promising and less invasive approach to diagnosis. This study aims to develop an ultra-sensitive assay for detecting melanoma NRAS mutant ctDNA.

Methods

To detect rare NRAS mutant ctDNA, we developed the NRAS PASEA assay by screening CRISPR-Cas proteins that recognize the PAM sequence 5′-TTN-3′. This method employs CRISPR-Cas proteins to continuously shear wild-type alleles during isothermal amplification, resulting in exponential amplification of mutant alleles to a detectable level by Sanger sequencing.

Results

The developed NRAS Q61R/L/K mutation detection method can detect simulated ctDNA samples with mutant allele fractions (MAF) as low as 0.01 % with 30 mins of PASEA treatment. Notably, the NRAS Q61 K mutation was accurately identified by FnCas12a-based NRAS PASEA, even with the nucleotide at the "N" position in the PAM site "TTN." The method successfully detected ctDNA in patients with malignant melanoma. All patients (5/5) from 15 melanoma blood samples with NRAS Q61R (4/4) and NRAS Q61 K (1/1) mutations were accurately identified, with no false positives among patients with wildtype NRAS Q61.

Conclusion

Detecting ctDNA from peripheral blood samples is highly significant for melanomas in areas where imaging evaluation is challenging. Our assay demonstrated 100 % consistency with tumor tissue NGS, providing a new analytical strategy for companion diagnosis and dynamic assessment of therapeutic efficacy and disease progression in melanoma.

{"title":"Ultra-sensitive detection of melanoma NRAS mutant ctDNA based on programmable endonucleases","authors":"Zuoying Zhang , Qing Ji , Zhanfang Zhang , Bao Lyu , Pei Li , Liyi Zhang , Kaifei Chen , Meiyu Fang , Jinzhao Song","doi":"10.1016/j.cancergen.2025.02.008","DOIUrl":"10.1016/j.cancergen.2025.02.008","url":null,"abstract":"<div><h3>Background</h3><div>Melanoma is a complex and often fatal disease, with NRAS being one of the most frequently mutated genes in this type of cancer. Liquid biopsies, specifically tests for circulating tumor DNA (ctDNA), represent a promising and less invasive approach to diagnosis. This study aims to develop an ultra-sensitive assay for detecting melanoma NRAS mutant ctDNA.</div></div><div><h3>Methods</h3><div>To detect rare NRAS mutant ctDNA, we developed the NRAS PASEA assay by screening CRISPR-Cas proteins that recognize the PAM sequence 5′-TTN-3′. This method employs CRISPR-Cas proteins to continuously shear wild-type alleles during isothermal amplification, resulting in exponential amplification of mutant alleles to a detectable level by Sanger sequencing.</div></div><div><h3>Results</h3><div>The developed NRAS Q61R/L/K mutation detection method can detect simulated ctDNA samples with mutant allele fractions (MAF) as low as 0.01 % with 30 mins of PASEA treatment. Notably, the NRAS Q61 K mutation was accurately identified by FnCas12a-based NRAS PASEA, even with the nucleotide at the \"N\" position in the PAM site \"TTN.\" The method successfully detected ctDNA in patients with malignant melanoma. All patients (5/5) from 15 melanoma blood samples with NRAS Q61R (4/4) and NRAS Q61 K (1/1) mutations were accurately identified, with no false positives among patients with wildtype NRAS Q61.</div></div><div><h3>Conclusion</h3><div>Detecting ctDNA from peripheral blood samples is highly significant for melanomas in areas where imaging evaluation is challenging. Our assay demonstrated 100 % consistency with tumor tissue NGS, providing a new analytical strategy for companion diagnosis and dynamic assessment of therapeutic efficacy and disease progression in melanoma.</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"294 ","pages":"Pages 47-56"},"PeriodicalIF":1.4,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143704633","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

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