Pub Date : 2025-07-17DOI: 10.1016/j.cancergen.2025.07.010
Atika Dogra , Yasha Hasija
Oral cancer is among the top malignancies and the leading cause of death worldwide. Poor outcomes are attributed to local recurrence and distant metastasis of disease. There is an urgent need to identify the potential biomarkers that may help in prognostication and management of oral cancer. This study aimed to find potential prognostic biomarkers for oral squamous cell carcinoma (OSCC) using eXplainable artificial intelligence (XAI). After the curation of microarray data from GSE31056 (38 relapsed and 58 non-relapsed OSCC samples/ normal oral tissue samples), the application of XAI on Extreme Gradient Boosting algorithm machine learning (ML) models trained on binary classification datasets was employed. After successfully incorporating SHapley Additive exPlanations values into the ML models, 20 top significant genes associated with the relapse of OSCC were identified. The key genes included FAM49B, TTC39A, IFI16, ANGPTL4, HSPH1, GRIA2, SERF2 and others which contribute crucially to cell growth, cell invasion, apoptosis, disease progression, overall survival and disease-free survival. Further, a network of genes and their targeting microRNAs (miRNAs) revealed that miRNAs hsa-let-7b-5p, hsa-miR-27a-3p and hsa-miR-124–3p, had the highest interactions with genes. The predicted genes and miRNAs might be worthy prognostic markers and open the possibilities to understand the underlying pathways and recognize therapeutic targets for aggressive OSCC.
{"title":"Unraveling prognostic biomarkers in oral squamous cell carcinoma: An approach based on explainable artificial intelligence","authors":"Atika Dogra , Yasha Hasija","doi":"10.1016/j.cancergen.2025.07.010","DOIUrl":"10.1016/j.cancergen.2025.07.010","url":null,"abstract":"<div><div>Oral cancer is among the top malignancies and the leading cause of death worldwide. Poor outcomes are attributed to local recurrence and distant metastasis of disease. There is an urgent need to identify the potential biomarkers that may help in prognostication and management of oral cancer. This study aimed to find potential prognostic biomarkers for oral squamous cell carcinoma (OSCC) using eXplainable artificial intelligence (XAI). After the curation of microarray data from GSE31056 (38 relapsed and 58 non-relapsed OSCC samples/ normal oral tissue samples), the application of XAI on Extreme Gradient Boosting algorithm machine learning (ML) models trained on binary classification datasets was employed. After successfully incorporating SHapley Additive exPlanations values into the ML models, 20 top significant genes associated with the relapse of OSCC were identified. The key genes included FAM49B, TTC39A, IFI16, ANGPTL4, HSPH1, GRIA2, SERF2 and others which contribute crucially to cell growth, cell invasion, apoptosis, disease progression, overall survival and disease-free survival. Further, a network of genes and their targeting microRNAs (miRNAs) revealed that miRNAs hsa-let-7b-5p, hsa-miR-27a-3p and hsa-miR-124–3p, had the highest interactions with genes. The predicted genes and miRNAs might be worthy prognostic markers and open the possibilities to understand the underlying pathways and recognize therapeutic targets for aggressive OSCC.</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"296 ","pages":"Pages 163-171"},"PeriodicalIF":1.4,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144703087","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}
Pub Date : 2025-07-16DOI: 10.1016/j.cancergen.2025.07.009
Qiong Wei , Yi Yang , Huimin Wang, Chun Li, Yuping Li
Objective
Ovarian cancer (OC) is the foremost cause of gynecological cancer-related mortality. Respecting the role of long noncoding RNAs (lncRNAs) in malignancies, we explored the mechanism of SSTR5-AS1 regulating OC cell ferroptosis resistance and immune escape via the signal transducer and activator of transcription 3 (STAT3)/solute carrier family 7a member 11 (SLC7A11) axis.
Methods
OC cells were treated with si-SSTR5-AS1, oe-SSTR5-AS1 and oe-SLC7A11 plasmids. SSTR5-AS1, STAT3 and SLC7A11 mRNA levels, and cell malignant behaviors were assessed by RT-qPCR, CCK-8 and Transwell assays. Fe2+, glutathione (GSH) and malondialdehyde (MDA) levels in Erastin-induced OC cells, and viability and apoptosis in OC cell-co-cultured CD8+T cells were determined using kits, and CCK-8 and flow cytometry. SSTR5-AS1 distribution was detected by subcellular fractionation assay. STAT3 and SLC7A11 protein levels were measured by Western blot. The protein interaction and binding relationship between SSTR5-AS1 and STAT3 were predicted by database and confirmed using RIP and verified using dual-luciferase assays.
Results
SSTR5-AS1 was up-regulated in OC cells. SSTR5-AS1 overexpression facilitated OC cell malignant behaviors, down-regulated Fe2+ and MDA levels and up-regulated the GSH level in Erastin-treated OC cells, and diminished viability and enhanced apoptosis in OC cell-co-cultured CD8+T cells, suggesting that SSTR5-AS1 overexpression promoted OC cell ferroptosis resistance and immune escape, which were inhibited by its downregulation. SSTR5-AS1 facilitated SLC7A11 transcription and expression by recruiting STAT3. SLC7A11 overexpression partially reversed the effects of SSTR5-AS1 knockdown on OC cells.
Conclusion
SSTR5-AS1 promoted SLC7A11 transcription and expression by recruiting STAT3, thereby promoting ferroptosis resistance and immune escape of OC cells.
{"title":"The mechanism of lncRNA SSTR5-AS1 promoting ferroptosis resistance and immune escape in ovarian cancer cells by recruiting STAT3 to regulate SLC7A11 expression","authors":"Qiong Wei , Yi Yang , Huimin Wang, Chun Li, Yuping Li","doi":"10.1016/j.cancergen.2025.07.009","DOIUrl":"10.1016/j.cancergen.2025.07.009","url":null,"abstract":"<div><h3>Objective</h3><div>Ovarian cancer (OC) is the foremost cause of gynecological cancer-related mortality. Respecting the role of long noncoding RNAs (lncRNAs) in malignancies, we explored the mechanism of SSTR5-AS1 regulating OC cell ferroptosis resistance and immune escape via the signal transducer and activator of transcription 3 (STAT3)/solute carrier family 7a member 11 (SLC7A11) axis.</div></div><div><h3>Methods</h3><div>OC cells were treated with si-SSTR5-AS1, oe-SSTR5-AS1 and oe-SLC7A11 plasmids. SSTR5-AS1, STAT3 and SLC7A11 mRNA levels, and cell malignant behaviors were assessed by RT-qPCR, CCK-8 and Transwell assays. Fe<sup>2+</sup>, glutathione (GSH) and malondialdehyde (MDA) levels in Erastin-induced OC cells, and viability and apoptosis in OC cell-co-cultured CD8<sup>+</sup><em>T</em> cells were determined using kits, and CCK-8 and flow cytometry. SSTR5-AS1 distribution was detected by subcellular fractionation assay. STAT3 and SLC7A11 protein levels were measured by Western blot. The protein interaction and binding relationship between SSTR5-AS1 and STAT3 were predicted by database and confirmed using RIP and verified using dual-luciferase assays.</div></div><div><h3>Results</h3><div>SSTR5-AS1 was up-regulated in OC cells. SSTR5-AS1 overexpression facilitated OC cell malignant behaviors, down-regulated Fe<sup>2+</sup> and MDA levels and up-regulated the GSH level in Erastin-treated OC cells, and diminished viability and enhanced apoptosis in OC cell-co-cultured CD8<sup>+</sup><em>T</em> cells, suggesting that SSTR5-AS1 overexpression promoted OC cell ferroptosis resistance and immune escape, which were inhibited by its downregulation. SSTR5-AS1 facilitated SLC7A11 transcription and expression by recruiting STAT3. SLC7A11 overexpression partially reversed the effects of SSTR5-AS1 knockdown on OC cells.</div></div><div><h3>Conclusion</h3><div>SSTR5-AS1 promoted SLC7A11 transcription and expression by recruiting STAT3, thereby promoting ferroptosis resistance and immune escape of OC cells.</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"296 ","pages":"Pages 172-181"},"PeriodicalIF":1.4,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144711966","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}
Pub Date : 2025-07-10DOI: 10.1016/j.cancergen.2025.07.007
Yakup Akkoç , Hasan Sulhan , Ersin Akgöllü , Ali Çift
Background
The age-adjusted rate of Bladder cancer (BC) in Türkiye is quite high, and genetic factors are effective in BC. Long non-coding RNAs (lncRNAs) synthesized from the HOTAIR gene have been shown to promote tumor progression in many cancers. rs874945 and rs4759314 polymorphisms in the HOTAIR gene cause changes in the expression levels of lncRNAs synthesized from this gene. The aim of this study was to explore for the first time the association of these variants with BC in a Caucasian population.
Methods
The present study explored the HOTAIR gene polymorphisms in 98 BC patients and in 150 healthy individuals using real-time polymerase chain reaction (RT-PCR).
Results
Carrying rs874945 G allele and GA genotype increased the BC risk in the statistic models. However, even if rs4759314 variant increased of BC risk was not significant. Similarly, although both polymorphisms increased clinicopathological features associated with poor prognosis, they were not statistically significant. Moreover, being older than 60 years and smoking are independent risk factors for BC.
Discussion
The current study is the first to show that patients carrying the G allele of the rs874945 polymorphism have a higher risk of BC in the Caucasian population. This work suggests that rs4759314 polymorphism should be studied in the Caucasian population with a larger sample size of BC patients.
{"title":"The effect of HOTAIR gene variants on the development of bladder cancer and its clinicopathological characteristics in a Caucasian population","authors":"Yakup Akkoç , Hasan Sulhan , Ersin Akgöllü , Ali Çift","doi":"10.1016/j.cancergen.2025.07.007","DOIUrl":"10.1016/j.cancergen.2025.07.007","url":null,"abstract":"<div><h3>Background</h3><div>The age-adjusted rate of Bladder cancer (BC) in Türkiye is quite high, and genetic factors are effective in BC. Long non-coding RNAs (lncRNAs) synthesized from the <em>HOTAIR</em> gene have been shown to promote tumor progression in many cancers. rs874945 and rs4759314 polymorphisms in the <em>HOTAIR</em> gene cause changes in the expression levels of lncRNAs synthesized from this gene. The aim of this study was to explore for the first time the association of these variants with BC in a Caucasian population.</div></div><div><h3>Methods</h3><div>The present study explored the <em>HOTAIR</em> gene polymorphisms in 98 BC patients and in 150 healthy individuals using real-time polymerase chain reaction (RT-PCR).</div></div><div><h3>Results</h3><div>Carrying rs874945 G allele and GA genotype increased the BC risk in the statistic models. However, even if rs4759314 variant increased of BC risk was not significant. Similarly, although both polymorphisms increased clinicopathological features associated with poor prognosis, they were not statistically significant. Moreover, being older than 60 years and smoking are independent risk factors for BC.</div></div><div><h3>Discussion</h3><div>The current study is the first to show that patients carrying the G allele of the rs874945 polymorphism have a higher risk of BC in the Caucasian population. This work suggests that rs4759314 polymorphism should be studied in the Caucasian population with a larger sample size of BC patients.</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"296 ","pages":"Pages 145-149"},"PeriodicalIF":1.4,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144662820","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}
Pub Date : 2025-07-09DOI: 10.1016/j.cancergen.2025.07.006
Junkyu Kim , Hye-Lim Jang , Jung Young Hong , Seung Tae Kim , Se Hoon Park , Joon Oh Park , Kyoung-Mee Kim , Deok geun Kim , Jeeyun Lee , Sung Hee Lim
Background
Activation of the phosphatidylinositol 3-kinase (PI3K) pathway is a common oncogenic mechanism in various solid tumors and is often driven by aberrations in the PIK3CA gene. Recent advancements have shown effective treatment for patients with PIK3CA-mutated breast cancer; however, there is an unmet need for other malignancies. The aim of this study was to gain a better understanding of PIK3CA mutations and amplifications across cancer types.
Methods
From October 2019 to June 2023, we performed next-generation sequencing using Trusight Oncology 500 on 3886 patients with 36 different cancer types at the Samsung Medical Center. The incidence of PIK3CA mutations and amplifications according to cancer type and their correlation with the tumor mutation burden (TMB), microsatellite instability (MSI), and homologous recombination deficiency (HRD) status were reviewed. Mutation sites were also identified.
Results
Among the 3886 patients, PIK3CA mutations were present in 9.2 % (358/3886) of the cohort, with colorectal cancer, 52.8 % (189/358), having the highest incidence. Patients harboring PIK3CA mutations demonstrated significantly higher TMB and MSI-high rates than those without (31.8 % vs. 12.5 % for TMB and 7.8 % vs. 1.6 % for MSI-high, respectively, p = 0.001). In contrast, PIK3CA amplifications were observed in 1.3 % (51/3886) of patients, primarily in gastric, bladder, and colorectal cancers, and associated with lower TMB, MSI-high, and HRD rates. PIK3CA fusions were identified in three patients. The most common mutation sites were E545K, E542K, and H1047R.
Conclusion
Of 3886 patients with metastatic solid tumors, 358(9.2 %) had PIK3CA mutations and 51(1.3 %) had PIK3CA amplifications. Next-generation sequencing analysis provided a deeper understanding of PIK3CA aberrations.
磷脂酰肌醇3-激酶（PI3K）途径的激活是各种实体肿瘤中常见的致癌机制，通常由PIK3CA基因畸变驱动。最近的进展表明pik3ca突变乳腺癌患者的有效治疗；然而，对其他恶性肿瘤的需求尚未得到满足。这项研究的目的是为了更好地了解PIK3CA突变和不同癌症类型的扩增。方法2019年10月至2023年6月，利用Trusight Oncology 500对三星首尔医院36种不同癌症类型的3886例患者进行了新一代测序。本文综述了PIK3CA突变和扩增的发生率及其与肿瘤突变负荷（TMB）、微卫星不稳定性（MSI）和同源重组缺陷（HRD）状态的相关性。突变位点也被确定。结果3886例患者中，PIK3CA突变发生率为9.2%(358/3886)，其中结直肠癌发生率最高，为52.8%（189/358）。携带PIK3CA突变的患者TMB和MSI-high的发生率明显高于未携带PIK3CA突变的患者（分别为31.8% vs 12.5% TMB和7.8% vs 1.6% MSI-high, p = 0.001）。相比之下，在1.3%（51/3886）的患者中观察到PIK3CA扩增，主要是在胃癌，膀胱癌和结直肠癌中，并且与较低的TMB， MSI-high和HRD发生率相关。在3例患者中发现了PIK3CA融合。最常见的突变位点为E545K、E542K和H1047R。结论3886例转移性实体瘤患者中，358例（9.2%）存在PIK3CA突变，51例（1.3%）存在PIK3CA扩增。下一代测序分析提供了对PIK3CA畸变更深入的了解。
{"title":"Prevalence and clinical implications of PIK3CA aberrations across cancer types: A real-world next-generation sequencing approach","authors":"Junkyu Kim , Hye-Lim Jang , Jung Young Hong , Seung Tae Kim , Se Hoon Park , Joon Oh Park , Kyoung-Mee Kim , Deok geun Kim , Jeeyun Lee , Sung Hee Lim","doi":"10.1016/j.cancergen.2025.07.006","DOIUrl":"10.1016/j.cancergen.2025.07.006","url":null,"abstract":"<div><h3>Background</h3><div>Activation of the phosphatidylinositol 3-kinase (PI3K) pathway is a common oncogenic mechanism in various solid tumors and is often driven by aberrations in the <em>PIK3CA</em> gene. Recent advancements have shown effective treatment for patients with <em>PIK3CA</em>-mutated breast cancer; however, there is an unmet need for other malignancies. The aim of this study was to gain a better understanding of PIK3CA mutations and amplifications across cancer types.</div></div><div><h3>Methods</h3><div>From October 2019 to June 2023, we performed next-generation sequencing using Trusight Oncology 500 on 3886 patients with 36 different cancer types at the Samsung Medical Center. The incidence of <em>PIK3CA</em> mutations and amplifications according to cancer type and their correlation with the tumor mutation burden (TMB), microsatellite instability (MSI), and homologous recombination deficiency (HRD) status were reviewed. Mutation sites were also identified.</div></div><div><h3>Results</h3><div>Among the 3886 patients, <em>PIK3CA</em> mutations were present in 9.2 % (358/3886) of the cohort, with colorectal cancer, 52.8 % (189/358), having the highest incidence. Patients harboring <em>PIK3CA</em> mutations demonstrated significantly higher TMB and MSI-high rates than those without (31.8 % vs. 12.5 % for TMB and 7.8 % vs. 1.6 % for MSI-high, respectively, <em>p</em> = 0.001). In contrast, <em>PIK3CA</em> amplifications were observed in 1.3 % (51/3886) of patients, primarily in gastric, bladder, and colorectal cancers, and associated with lower TMB, MSI-high, and HRD rates. PIK3CA fusions were identified in three patients. The most common mutation sites were E545K, E542K, and H1047R.</div></div><div><h3>Conclusion</h3><div>Of 3886 patients with metastatic solid tumors, 358(9.2 %) had <em>PIK3CA</em> mutations and 51(1.3 %) had PIK3CA amplifications. Next-generation sequencing analysis provided a deeper understanding of PIK3CA aberrations.</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"296 ","pages":"Pages 133-143"},"PeriodicalIF":1.4,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144656551","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}
Pub Date : 2025-07-07DOI: 10.1016/j.cancergen.2025.07.005
Vahid Rouhi , Sanaz Habibi , Dr. Hikmet Koseoglu , Dr. Emre Ari , Mehmet Guven
Prostate cancer is the second most common malignancy and a major cause of cancerrelated deaths in men. Dysregulation of DNA repair mechanisms, particularly those involved in base excision repair (BER), contributes significantly to carcinogenesis. Alterations in this pathway have been linked to aggressive tumor behavior, early recurrence, and poor survival, positioning DNA repair as a promising therapeutic target. This study focused on the expression of two BER genes, uracil DNA glycosylase (UNG) and 8-oxoguanine DNA glycosylase (OGG1), in tumor and adjacent normal prostate tissues. Fifty prostate cancer patients were enrolled. Tumor and adjacent normal tissues were obtained using tru-cut biopsy. Gene expression levels of UNG and OGG1 were assessed by quantitative real-time PCR. UNG expression was significantly elevated in tumor tissues compared to normal tissues, showing a 3.39-fold increase (p = 0.02). OGG1 expression also increased by 2.60-fold, but this was not statistically significant (p > 0.05). A positive correlation was observed between UNG expression and PSA levels in tumor tissues (r = 0.341, p = 0.01). No statistically significant difference in gene expression was found between tumor and normal tissues with respect to clinical parameters such as diabetes, hypertension, PIRADS score, Gleason score, smoking status, or presence of nodules. UNG is significantly upregulated in prostate cancer and may help maintain genomic stability and tumor cell survival. Targeting UNG alongside DNA-damaging therapies could disrupt cancer progression. Further studies on BER genes may support personalized treatment approaches in prostate cancer.
前列腺癌是第二常见的恶性肿瘤，也是男性癌症相关死亡的主要原因。DNA修复机制的失调，特别是涉及碱基切除修复（BER）的DNA修复机制的失调，对癌症的发生起着重要的作用。这一通路的改变与肿瘤的侵袭性行为、早期复发和较差的生存率有关，这使得DNA修复成为一个有希望的治疗靶点。本研究重点研究了尿嘧啶DNA糖基化酶（UNG）和8-氧鸟嘌呤DNA糖基化酶（OGG1）两个BER基因在肿瘤和邻近正常前列腺组织中的表达。50名前列腺癌患者被纳入研究。采用真切活检法获得肿瘤及邻近正常组织。采用实时荧光定量PCR检测UNG和OGG1基因表达水平。与正常组织相比，UNG在肿瘤组织中的表达明显升高，为3.39倍（p = 0.02）。OGG1表达量也增加了2.60倍，但差异无统计学意义(p >；0.05)。肿瘤组织中UNG表达与PSA水平呈正相关（r = 0.341, p = 0.01）。在临床参数如糖尿病、高血压、PIRADS评分、Gleason评分、吸烟状况或结节的存在等方面，肿瘤组织与正常组织的基因表达无统计学差异。UNG在前列腺癌中显著上调，可能有助于维持基因组稳定性和肿瘤细胞存活。靶向UNG和dna损伤疗法可能会破坏癌症的进展。对BER基因的进一步研究可能支持前列腺癌的个性化治疗方法。
{"title":"Upregulation of Uracil DNA Glycosylase (UNG) in Prostate Cancer","authors":"Vahid Rouhi , Sanaz Habibi , Dr. Hikmet Koseoglu , Dr. Emre Ari , Mehmet Guven","doi":"10.1016/j.cancergen.2025.07.005","DOIUrl":"10.1016/j.cancergen.2025.07.005","url":null,"abstract":"<div><div>Prostate cancer is the second most common malignancy and a major cause of cancerrelated deaths in men. Dysregulation of DNA repair mechanisms, particularly those involved in base excision repair (BER), contributes significantly to carcinogenesis. Alterations in this pathway have been linked to aggressive tumor behavior, early recurrence, and poor survival, positioning DNA repair as a promising therapeutic target. This study focused on the expression of two BER genes, uracil DNA glycosylase (UNG) and 8-oxoguanine DNA glycosylase (OGG1), in tumor and adjacent normal prostate tissues. Fifty prostate cancer patients were enrolled. Tumor and adjacent normal tissues were obtained using tru-cut biopsy. Gene expression levels of UNG and OGG1 were assessed by quantitative real-time PCR. UNG expression was significantly elevated in tumor tissues compared to normal tissues, showing a 3.39-fold increase (<em>p</em> = 0.02). OGG1 expression also increased by 2.60-fold, but this was not statistically significant (<em>p</em> > 0.05). A positive correlation was observed between UNG expression and PSA levels in tumor tissues (<em>r</em> = 0.341, <em>p</em> = 0.01). No statistically significant difference in gene expression was found between tumor and normal tissues with respect to clinical parameters such as diabetes, hypertension, PIRADS score, Gleason score, smoking status, or presence of nodules. UNG is significantly upregulated in prostate cancer and may help maintain genomic stability and tumor cell survival. Targeting UNG alongside DNA-damaging therapies could disrupt cancer progression. Further studies on BER genes may support personalized treatment approaches in prostate cancer.</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"296 ","pages":"Pages 130-132"},"PeriodicalIF":1.4,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144611724","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}
Pub Date : 2025-07-07DOI: 10.1016/j.cancergen.2025.07.002
B Aldrige Allister , Jonathan L Lühmann , Lena Wendeburg , Frank Dechend , Carmela Beger , Stefanie Tölle , Julia von Ehr , Tim Ripperger , Bernd Auber , Nataliya di Donato , Doris Steinemann
Large genomic rearrangements (LGRs) within the human genome are becoming more recognized by novel genome-wide technologies and may be underreported so far. This class of genomic variation includes copy number variations like duplications or triplications of coding or non-coding genomic regions. Here, we report two LGRs targeting BRCA1, a duplication of exons 18–19 and a triplication of exons 1–2 in two independent families. Utilizing Optical Genome Mapping (OGM), Whole Genome Sequencing (WGS) and cDNA analysis, we characterized the genomic organization and transcriptomic effects of these LGRs regarding its. We show that the tandem duplication ogm[GRCh38]dup(17)(q21.31q21.31)(43057052_43063373), targeting BRCA1 exon 18–19 is predicted to generate a premature termination codon, namely p.(His1732Metfs*10). The triplication of BRCA1 exon 1–2 ogm[GRCh38]trip(17)(q21.31q21.31)(43117155_43124115) is also sequentially arranged. The transcript shows an insertion of a small part of intron 2 (chr17:43,121,558–43,121,676) that theoretically will generate a premature termination codon as well. Collectively, OGM and WGS help elucidating the architecture of these LGRs. However, the final curation depends on how adequate the functional consequences of these LGR can be clarified. Deeper investigation of LGRs on transcript level is important to attain accurate conclusions with respect to therapeutic decisions.
{"title":"Tandem duplication and triplication in BRCA1: revisiting the large genomic rearrangements via optical genome mapping","authors":"B Aldrige Allister , Jonathan L Lühmann , Lena Wendeburg , Frank Dechend , Carmela Beger , Stefanie Tölle , Julia von Ehr , Tim Ripperger , Bernd Auber , Nataliya di Donato , Doris Steinemann","doi":"10.1016/j.cancergen.2025.07.002","DOIUrl":"10.1016/j.cancergen.2025.07.002","url":null,"abstract":"<div><div>Large genomic rearrangements (LGRs) within the human genome are becoming more recognized by novel genome-wide technologies and may be underreported so far. This class of genomic variation includes copy number variations like duplications or triplications of coding or non-coding genomic regions. Here, we report two LGRs targeting <em>BRCA1</em>, a duplication of exons 18–19 and a triplication of exons 1–2 in two independent families. Utilizing Optical Genome Mapping (OGM), Whole Genome Sequencing (WGS) and cDNA analysis, we characterized the genomic organization and transcriptomic effects of these LGRs regarding its. We show that the tandem duplication ogm[GRCh38]dup(17)(q21.31q21.31)(43057052_43063373), targeting <em>BRCA1</em> exon 18–19 is predicted to generate a premature termination codon, namely p.(His1732Metfs*10). The triplication of <em>BRCA1</em> exon 1–2 ogm[GRCh38]trip(17)(q21.31q21.31)(43117155_43124115) is also sequentially arranged. The transcript shows an insertion of a small part of intron 2 (chr17:43,121,558–43,121,676) that theoretically will generate a premature termination codon as well. Collectively, OGM and WGS help elucidating the architecture of these LGRs. However, the final curation depends on how adequate the functional consequences of these LGR can be clarified. Deeper investigation of LGRs on transcript level is important to attain accurate conclusions with respect to therapeutic decisions.</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"296 ","pages":"Pages 125-129"},"PeriodicalIF":1.4,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144614664","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}
TFAP2E, a member of the activator protein-2 transcription factor family, is considered to act as a tumor suppressor. Lower TFAP2E expression is associated with poor prognosis in patients with different cancer types. TFAP2E gene is located on chromosome 1q34, where is commonly deleted region in the cancer genome. Our previous research indicated that TFAP2E suppresses cell growth by regulating cell cycle progression from the G2 to M phase. However, as the analyses were performed using asynchronized cells, other possibilities cannot be ruled out. The present study aimed to analyze the effects of TFAP2E silencing on synchronized cells. Human oral squamous cell carcinoma (OSCC)-derived Ca9–22 cells were stably transfected with TFAP2E-short hairpin RNA and synchronized to the late-G1 phase using double thymidine block. Cell cycle progression rate was analyzed by periodically examining cell cycle distribution patterns using fluorescence-activated cell sorting analysis. TFAP2E-knockdown cells showed a rapid exit from the M-phase compared with control cells; meanwhile, no difference was observed between the cells until the end of S-phase. Additionally, rapid M-phase exit was not observed in TFAP2E-knockdown cells following release from nocodazole-mediated synchronization to the G2/M-phase. These observations indicated that TFAP2E-knockdown results in rapid cell cycle progression from the G2 to M phase. Overall, current findings suggest that TFAP2E acts as a tumor suppressor by regulating cell cycle progression at least in OSCC cells.
{"title":"TFAP2E acts as a tumor suppressor by regulating cell cycle progression in oral squamous cell carcinoma cells","authors":"Ryo Sakai , Yoshinori Inagaki , Haruno Tsurumi , Akiko Ohashi , Tadateru Takayama , Shuichi Sato , Kyoko Fujiwara","doi":"10.1016/j.cancergen.2025.07.004","DOIUrl":"10.1016/j.cancergen.2025.07.004","url":null,"abstract":"<div><div>TFAP2E, a member of the activator protein-2 transcription factor family, is considered to act as a tumor suppressor. Lower TFAP2E expression is associated with poor prognosis in patients with different cancer types. <em>TFAP2E</em> gene is located on chromosome 1q34, where is commonly deleted region in the cancer genome. Our previous research indicated that TFAP2E suppresses cell growth by regulating cell cycle progression from the G2 to M phase. However, as the analyses were performed using asynchronized cells, other possibilities cannot be ruled out. The present study aimed to analyze the effects of <em>TFAP2E</em> silencing on synchronized cells. Human oral squamous cell carcinoma (OSCC)-derived Ca9–22 cells were stably transfected with TFAP2E-short hairpin RNA and synchronized to the late-G1 phase using double thymidine block. Cell cycle progression rate was analyzed by periodically examining cell cycle distribution patterns using fluorescence-activated cell sorting analysis. TFAP2E-knockdown cells showed a rapid exit from the M-phase compared with control cells; meanwhile, no difference was observed between the cells until the end of S-phase. Additionally, rapid M-phase exit was not observed in TFAP2E-knockdown cells following release from nocodazole-mediated synchronization to the G2/M-phase. These observations indicated that TFAP2E-knockdown results in rapid cell cycle progression from the G2 to M phase. Overall, current findings suggest that TFAP2E acts as a tumor suppressor by regulating cell cycle progression at least in OSCC cells.</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"296 ","pages":"Pages 111-116"},"PeriodicalIF":1.4,"publicationDate":"2025-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144596505","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}
Pub Date : 2025-07-05DOI: 10.1016/j.cancergen.2025.07.003
Jennifer YM Ling , Kirk AJ Stephenson , Tammy L Romanuik , My Linh Thibodeau , Maryam Soleimani , Katherine E Paton
As multigene panel genetic testing for hereditary cancer syndromes increases in clinical use, the detection of unexpected secondary findings will occur more commonly. We present the case of a 40-year-old woman with breast cancer who harboured a secondary finding in the VHL gene variant without other cancer risk alleles (e.g., BRCA1/BRCA2) sufficient to explain her primary presentation. Subsequent exam revealed ophthalmic manifestations of von Hippel-Lindau syndrome (VHLS), emphasizing the importance of multidisciplinary clinical assessment and phenotyping. The development of retinal and central nervous system hemangioblastomas, clear cell renal cell carcinomas, pancreatic neuroendocrine tumours and phaeochromocytomas are characteristic of VHLS, but the link with breast cancer is poorly understood. Though the benefit of hereditary cancer genetic testing is well-known, this case highlights the importance of pre-test genetic counselling to prepare patients for all possible results, including additional unanticipated genetic diagnoses. Such pre-test counselling can set appropriate expectations for the possible requirement of ongoing surveillance and/or treatment.
{"title":"Detection of VHL variant on multigene panel testing for hereditary breast cancer: Implications for genetic counselling","authors":"Jennifer YM Ling , Kirk AJ Stephenson , Tammy L Romanuik , My Linh Thibodeau , Maryam Soleimani , Katherine E Paton","doi":"10.1016/j.cancergen.2025.07.003","DOIUrl":"10.1016/j.cancergen.2025.07.003","url":null,"abstract":"<div><div>As multigene panel genetic testing for hereditary cancer syndromes increases in clinical use, the detection of unexpected secondary findings will occur more commonly. We present the case of a 40-year-old woman with breast cancer who harboured a secondary finding in the <em>VHL</em> gene variant without other cancer risk alleles (e.g., <em>BRCA1/BRCA2</em>) sufficient to explain her primary presentation. Subsequent exam revealed ophthalmic manifestations of von Hippel-Lindau syndrome (VHLS), emphasizing the importance of multidisciplinary clinical assessment and phenotyping. The development of retinal and central nervous system hemangioblastomas, clear cell renal cell carcinomas, pancreatic neuroendocrine tumours and phaeochromocytomas are characteristic of VHLS, but the link with breast cancer is poorly understood. Though the benefit of hereditary cancer genetic testing is well-known, this case highlights the importance of pre-test genetic counselling to prepare patients for all possible results, including additional unanticipated genetic diagnoses. Such pre-test counselling can set appropriate expectations for the possible requirement of ongoing surveillance and/or treatment.</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"296 ","pages":"Pages 150-153"},"PeriodicalIF":1.4,"publicationDate":"2025-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144670765","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}
Pub Date : 2025-07-03DOI: 10.1016/j.cancergen.2025.06.010
Dehua Zeng , Shixin Ye , Wenmin Yin , Duohuang Lian , Shunkai Zhou
Objective
This study aimed to identify biomarkers of esophageal cancer and elucidate their mechanisms of action in esophageal cancer.
Methods
Differential protein expression between esophageal tumor tissue and adjacent normal tissue was analyzed using proteomics in a mouse model of esophageal cancer. Differential proteins were identified through bioinformatics analysis. The mechanisms of action of differential proteins in esophageal cancer were validated using techniques such as western blotting and immunohistochemistry.
Results
Proteomic analysis revealed that IL-38 exhibited the greatest differential expression. Molecular biology techniques including western blotting and immunohistochemistry demonstrated that IL-38 modulates Regulatory T cell (Treg)/ T helper 17 cell (Th17) balance through the Sirtuin 1 (SIRT1)/ hypoxia-inducible factor 1-alpha (HIF-1α) signaling pathway in esophageal cancer.
Conclusion
IL-38 is a novel biomarker for esophageal cancer and regulates Treg/Th17 balance through the Sirt1/HIF-1α signaling pathway, providing new insights for the treatment of esophageal cancer.
{"title":"Influence of IL-38 as a novel biomarker on the pathophysiological processes of esophageal cancer","authors":"Dehua Zeng , Shixin Ye , Wenmin Yin , Duohuang Lian , Shunkai Zhou","doi":"10.1016/j.cancergen.2025.06.010","DOIUrl":"10.1016/j.cancergen.2025.06.010","url":null,"abstract":"<div><h3>Objective</h3><div>This study aimed to identify biomarkers of esophageal cancer and elucidate their mechanisms of action in esophageal cancer.</div></div><div><h3>Methods</h3><div>Differential protein expression between esophageal tumor tissue and adjacent normal tissue was analyzed using proteomics in a mouse model of esophageal cancer. Differential proteins were identified through bioinformatics analysis. The mechanisms of action of differential proteins in esophageal cancer were validated using techniques such as western blotting and immunohistochemistry.</div></div><div><h3>Results</h3><div>Proteomic analysis revealed that IL-38 exhibited the greatest differential expression. Molecular biology techniques including western blotting and immunohistochemistry demonstrated that IL-38 modulates Regulatory T cell (Treg)/ T helper 17 cell (Th17) balance through the Sirtuin 1 (SIRT1)/ hypoxia-inducible factor 1-alpha (HIF-1α) signaling pathway in esophageal cancer.</div></div><div><h3>Conclusion</h3><div>IL-38 is a novel biomarker for esophageal cancer and regulates Treg/Th17 balance through the Sirt1/HIF-1α signaling pathway, providing new insights for the treatment of esophageal cancer.</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"296 ","pages":"Pages 117-124"},"PeriodicalIF":1.4,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144596506","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}
Pub Date : 2025-07-01DOI: 10.1016/j.cancergen.2025.06.011
Bulent Tekin , Seda Ekizoglu , Sare Burcu Kaya , Mehmet Guven , Didem Can Trabulus
RNA editing mediated by ADAR1 is vital for the survival of mammals, and its malfunction leads to irregular editing of its targets, potentially influencing the observable characteristics of breast cancer. The study aims to investigate ADAR1- p110 and ADAR1-p150 gene expression in breast cancer patients' tissue samples (tumor and normal), to determine the role of this expression in tumor development, and to correlate expression levels with patients' clinical findings to understand breast cancer heterogeneity. In this research, we used tumor and adjacent normal tissue samples from 75 patients diagnosed with breast cancer who had undergone surgery. The levels of gene expression were determined using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The study found that ADAR1-p110 expression was significantly higher (1.32-fold, p < 0.0001) in tumor tissue compared to adjacent normal tissue. Similarly, ADAR1-p150 expression also showed a significant increase (1.58-fold, p < 0.0001) in tumor tissue compared to normal tissue. ADAR1-p150 expression was significantly higher in ER (estrogen receptors )-positive patients compared to ER-negative patients (p = 0.04). Additionally, patients with lobular histology showed significantly higher ADAR1-p150 expression levels compared to those with ductal histology (p = 0.02). Our findings, obtained by using tumor and normal tissue from the same individual, demonstrate increased ADAR1 gene expression in tumor tissue. Considering the literature data indicating ADAR1′s association with drug resistance and the correlation we observed between ADAR1 expression levels and certain clinicopathological data of the patients, it is evident that ADAR1 expression is a parameter that should be taken into account in treatment planning.
{"title":"ADAR1 gene expression and its importance in breast cancer","authors":"Bulent Tekin , Seda Ekizoglu , Sare Burcu Kaya , Mehmet Guven , Didem Can Trabulus","doi":"10.1016/j.cancergen.2025.06.011","DOIUrl":"10.1016/j.cancergen.2025.06.011","url":null,"abstract":"<div><div>RNA editing mediated by ADAR1 is vital for the survival of mammals, and its malfunction leads to irregular editing of its targets, potentially influencing the observable characteristics of breast cancer. The study aims to investigate ADAR1- p110 and ADAR1-p150 gene expression in breast cancer patients' tissue samples (tumor and normal), to determine the role of this expression in tumor development, and to correlate expression levels with patients' clinical findings to understand breast cancer heterogeneity. In this research, we used tumor and adjacent normal tissue samples from 75 patients diagnosed with breast cancer who had undergone surgery. The levels of gene expression were determined using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The study found that ADAR1-p110 expression was significantly higher (1.32-fold, <em>p</em> < 0.0001) in tumor tissue compared to adjacent normal tissue. Similarly, ADAR1-p150 expression also showed a significant increase (1.58-fold, <em>p</em> < 0.0001) in tumor tissue compared to normal tissue. ADAR1-p150 expression was significantly higher in ER (estrogen receptors )-positive patients compared to ER-negative patients (<em>p</em> = 0.04). Additionally, patients with lobular histology showed significantly higher ADAR1-p150 expression levels compared to those with ductal histology (<em>p</em> = 0.02). Our findings, obtained by using tumor and normal tissue from the same individual, demonstrate increased ADAR1 gene expression in tumor tissue. Considering the literature data indicating ADAR1′s association with drug resistance and the correlation we observed between ADAR1 expression levels and certain clinicopathological data of the patients, it is evident that ADAR1 expression is a parameter that should be taken into account in treatment planning.</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"296 ","pages":"Pages 106-110"},"PeriodicalIF":1.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144571030","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}
扫码关注我们
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号