Pub Date : 2025-08-11DOI: 10.1016/j.cancergen.2025.08.002
Diane M. Wilcock , Jian Zhao , H. Evin Gulbahce
{"title":"Corrigendum to “Resolving HER2 status in breast carcinoma patients with complete deletion of CEP17 in fluorescence in-situ hybridization assays” [Cancer Genetics, 296–297, 2025, 196-199]","authors":"Diane M. Wilcock , Jian Zhao , H. Evin Gulbahce","doi":"10.1016/j.cancergen.2025.08.002","DOIUrl":"10.1016/j.cancergen.2025.08.002","url":null,"abstract":"","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"296 ","pages":"Page 217"},"PeriodicalIF":2.1,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144810405","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 : 2025-07-26DOI: 10.1016/j.cancergen.2025.07.015
Diane M. Wilcock , Jian Zhao , H. Evin Gulbahce
Objectives
To assess the clinicopathologic features of breast cancers with complete CEP17 deletion and determine if alternative testing can resolve their HER2 status.
Methods
Cases with complete CEP17 deletion were identified, relevant clinicopathologic information was obtained, and fluorescence in-situ hybridization (FISH) was rerun with an alternative chromosome 17 control gene (RAI1, 17p11.2). One case was also evaluated by cytogenomic SNP microarray (CMA).
Results
Nine breast carcinoma cases were identified and displayed average HER2 copy numbers ranging from 1.1 to 4.7 (Average: 3.1). HER2 immunohistochemistry (IHC) result was available on 8/9 cases with 2/8 (25 %) displaying no staining, 2/8 (25 %%) displaying 1+ staining and 4/8 (50 %) with 2+ staining. ER and PR IHC were available on 8/9 cases 7/8 (87.5 %) were ER and/or PR positive. RAI1 was present in all cases and, if used in place of CEP17, the ASCO/CAP group classification would have been 2/9 (22.2 %) Group 1, 2/9 (22.2 %) Group 4, and 5/9 (55.6 %) Group 5. CMA confirmed complete CEP17 deletion in one case.
Conclusions
Alternative chromosome 17 markers and/or CMA may be needed to resolve HER2 status in patients with complete deletion of CEP17.
{"title":"Resolving HER2 status in breast carcinoma patients with complete deletion of CEP17 in fluorescence in-situ hybridization assays","authors":"Diane M. Wilcock , Jian Zhao , H. Evin Gulbahce","doi":"10.1016/j.cancergen.2025.07.015","DOIUrl":"10.1016/j.cancergen.2025.07.015","url":null,"abstract":"<div><h3>Objectives</h3><div>To assess the clinicopathologic features of breast cancers with complete CEP17 deletion and determine if alternative testing can resolve their HER2 status.</div></div><div><h3>Methods</h3><div>Cases with complete CEP17 deletion were identified, relevant clinicopathologic information was obtained, and fluorescence in-situ hybridization (FISH) was rerun with an alternative chromosome 17 control gene (RAI1, 17p11.2). One case was also evaluated by cytogenomic SNP microarray (CMA).</div></div><div><h3>Results</h3><div>Nine breast carcinoma cases were identified and displayed average <em>HER2</em> copy numbers ranging from 1.1 to 4.7 (Average: 3.1). HER2 immunohistochemistry (IHC) result was available on 8/9 cases with 2/8 (25 %) displaying no staining, 2/8 (25 %%) displaying 1+ staining and 4/8 (50 %) with 2+ staining. ER and PR IHC were available on 8/9 cases 7/8 (87.5 %) were ER and/or PR positive. RAI1 was present in all cases and, if used in place of CEP17, the ASCO/CAP group classification would have been 2/9 (22.2 %) Group 1, 2/9 (22.2 %) Group 4, and 5/9 (55.6 %) Group 5. CMA confirmed complete CEP17 deletion in one case.</div></div><div><h3>Conclusions</h3><div>Alternative chromosome 17 markers and/or CMA may be needed to resolve HER2 status in patients with complete deletion of CEP17.</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"296 ","pages":"Pages 196-199"},"PeriodicalIF":2.1,"publicationDate":"2025-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144721951","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}
Universal cancer screening based on methylation analysis of circulating cell-free DNA (cfDNA) enables multi-organ cancer detection, thereby reducing all-cause mortality and preventing cancer misdiagnosed by guideline-based cancer-specific screening. This study aims to establish a gene methylation panel for blood-based multi-cancer early detection.
Materials and methods
Bioinformatics analysis and in-house DNA sequencing of various human cancer cell lines and blood from healthy persons were carried out to identify candidate pan-cancer methylation sites. Methylation-sensitive restriction enzymes-quantitative PCR (MSRE-qPCR) was then used for DNA methylation analysis. Blood cfDNA from 103 patients with diverse cancer types and 40 healthy subjects was extracted for methylation analysis.
Results
By bioinformatics analysis and in-house DNA sequencing, we identified two candidates pan-cancer methylation sites, HIST1H4F and CDO1. A long stretch of methylation was found on the promoters of HIST1H4F and CDO1 across various cancer cell lines, while these genomic regions are unmethylated in healthy persons. When tested with clinical samples, the detection sensitivity and specificity of our gene methylation panel in detecting pan-cancer were 47.57 % and 90.00 %, respectively. When analyzed by cancer subtypes, the detection sensitivity was the highest in lung cancer (76.92 %), followed by colorectal cancer (63.64 %) and gastric cancer (50.00 %).
Conclusions
Our newly established gene methylation panel provides an alternative assay for multi-cancer screening tests. As no bisulfite conversion and invasive procedures are required, it can accelerate cancer diagnosis and streamline the operation for pan-cancer screening.
{"title":"Pan-cancer methylation analysis of circulating cell-free DNA","authors":"Wenjiao Dong , Cia-Hin Lau , Jiaqi Li , Zhihao Huang , Jiahui Li , Weidong Wu , Xiaoqing Chen , Yumei Huang , Xiaojun Huang , Meijing Xu , Haibao Zhu , Yuanlin Ding","doi":"10.1016/j.cancergen.2025.07.014","DOIUrl":"10.1016/j.cancergen.2025.07.014","url":null,"abstract":"<div><h3>Background</h3><div>Universal cancer screening based on methylation analysis of circulating cell-free DNA (cfDNA) enables multi-organ cancer detection, thereby reducing all-cause mortality and preventing cancer misdiagnosed by guideline-based cancer-specific screening. This study aims to establish a gene methylation panel for blood-based multi-cancer early detection.</div></div><div><h3>Materials and methods</h3><div>Bioinformatics analysis and in-house DNA sequencing of various human cancer cell lines and blood from healthy persons were carried out to identify candidate pan-cancer methylation sites. Methylation-sensitive restriction enzymes-quantitative PCR (MSRE-qPCR) was then used for DNA methylation analysis. Blood cfDNA from 103 patients with diverse cancer types and 40 healthy subjects was extracted for methylation analysis.</div></div><div><h3>Results</h3><div>By bioinformatics analysis and in-house DNA sequencing, we identified two candidates pan-cancer methylation sites, <em>HIST1H4F</em> and <em>CDO1</em>. A long stretch of methylation was found on the promoters of <em>HIST1H4F</em> and <em>CDO1</em> across various cancer cell lines, while these genomic regions are unmethylated in healthy persons. When tested with clinical samples, the detection sensitivity and specificity of our gene methylation panel in detecting pan-cancer were 47.57 % and 90.00 %, respectively. When analyzed by cancer subtypes, the detection sensitivity was the highest in lung cancer (76.92 %), followed by colorectal cancer (63.64 %) and gastric cancer (50.00 %).</div></div><div><h3>Conclusions</h3><div>Our newly established gene methylation panel provides an alternative assay for multi-cancer screening tests. As no bisulfite conversion and invasive procedures are required, it can accelerate cancer diagnosis and streamline the operation for pan-cancer screening.</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"296 ","pages":"Pages 182-195"},"PeriodicalIF":2.1,"publicationDate":"2025-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144721987","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}
DICER1 syndrome is a tumor-predisposition disorder caused by a germline pathogenic variant in DICER1. Pathogenic variants of DICER1 are the monogenic cause of various tumors including pleuropulmonary blastoma (PPB), ovarian sex cord-stromal tumors, and multinodular goiters. We present a family with a novel DICER1 pathogenic variant c.5528–2del who presents with development of isolated thyroid goiters/follicular adenoma. A 44 year old female presents with a past medical history of total thyroidectomy along with her 14-year-old son with a past history of multinodular thyroid goiter confirmed as multifocal follicular adenoma with papillary architecture and her 12-year-old daughter with a past history of multinodular thyroid goiter confirmed as diffuse nodular thyroid hyperplasia. No additional DICER1 syndrome presentations were observed. A genetics panel revealed that the mother, the 14-year-old son, and the 12-year-old daughter share a heterozygous DICER1 c.5528–2del variant, which has not been previously reported. In addition to our direct clinical observations from this family, genetic analysis via in silico prediction models, segregation analysis, and ACMG classification support this variant to be pathogenic. Given the absence of other DICER1 syndrome manifestations through human genetics evidence, this variant may be specifically associated with isolated multinodular goiters/follicular adenoma. Our findings contribute to the expanding genotype-phenotype correlation in DICER1 syndrome, providing new insights into its variable clinical presentation. Since not all variants are identical, reporting of these observations will advance precision medicine and benefit future patients through more accurate diagnosis, prognosis and personalized management strategies.
{"title":"Isolated multinodular goiter and follicular adenoma associated with a novel germline DICER1 variant: A benign presentation","authors":"Joshua Chang , Rachel Rabenn , Aditi Parikh , Chen-Han Wilfred Wu","doi":"10.1016/j.cancergen.2025.07.013","DOIUrl":"10.1016/j.cancergen.2025.07.013","url":null,"abstract":"<div><div><em>DICER1</em> syndrome is a tumor-predisposition disorder caused by a germline pathogenic variant in <em>DICER1</em>. Pathogenic variants of <em>DICER1</em> are the monogenic cause of various tumors including pleuropulmonary blastoma (PPB), ovarian sex cord-stromal tumors, and multinodular goiters. We present a family with a novel <em>DICER1</em> pathogenic variant c.5528–2del who presents with development of isolated thyroid goiters/follicular adenoma. A 44 year old female presents with a past medical history of total thyroidectomy along with her 14-year-old son with a past history of multinodular thyroid goiter confirmed as multifocal follicular adenoma with papillary architecture and her 12-year-old daughter with a past history of multinodular thyroid goiter confirmed as diffuse nodular thyroid hyperplasia. No additional <em>DICER1</em> syndrome presentations were observed. A genetics panel revealed that the mother, the 14-year-old son, and the 12-year-old daughter share a heterozygous <em>DICER1</em> c.5528–2del variant, which has not been previously reported. In addition to our direct clinical observations from this family, genetic analysis via in silico prediction models, segregation analysis, and ACMG classification support this variant to be pathogenic. Given the absence of other <em>DICER1</em> syndrome manifestations through human genetics evidence, this variant may be specifically associated with isolated multinodular goiters/follicular adenoma. Our findings contribute to the expanding genotype-phenotype correlation in <em>DICER1</em> syndrome, providing new insights into its variable clinical presentation. Since not all variants are identical, reporting of these observations will advance precision medicine and benefit future patients through more accurate diagnosis, prognosis and personalized management strategies.</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"296 ","pages":"Pages 200-204"},"PeriodicalIF":2.1,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144724597","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}
Development of multiple distinct, synchronous cancer types in a pediatric patient is very rare and should raise suspicion for an underlying genetic predisposition to cancer.
Case presentation
We present a previously healthy seven-year-old male who was diagnosed with diffuse large B cell lymphoma after a ruptured appendicitis. During the same hospitalization, he was diagnosed with a high-grade glioma. He underwent subsequent genetic testing, which showed compound heterozygosity for PMS2. He was ultimately diagnosed with Mismatch Repair Cancer Syndrome-4, a subtype of Constitutional Mismatch Repair Deficiency syndrome. His newly discovered cancer predisposition syndrome led to multiple additional family members receiving the same diagnosis, which was especially important in a sibling with leukemia who received hematopoietic stem cell transplantation from an unaffected sibling donor.
Conclusion
While rare, cancer predisposition syndromes should be suspected in pediatric patients presenting with two or more synchronous, distinct cancer types.
{"title":"Mismatch Repair Cancer Syndrome presenting as synchronous high-grade glioma and diffuse large B cell lymphoma in a pediatric patient","authors":"Margaret Massett , Nicole Kendel , Abdulrazak Alali , Erin Wright","doi":"10.1016/j.cancergen.2025.07.012","DOIUrl":"10.1016/j.cancergen.2025.07.012","url":null,"abstract":"<div><h3>Background</h3><div>Development of multiple distinct, synchronous cancer types in a pediatric patient is very rare and should raise suspicion for an underlying genetic predisposition to cancer.</div></div><div><h3>Case presentation</h3><div>We present a previously healthy seven-year-old male who was diagnosed with diffuse large B cell lymphoma after a ruptured appendicitis. During the same hospitalization, he was diagnosed with a high-grade glioma. He underwent subsequent genetic testing, which showed compound heterozygosity for <em>PMS2</em>. He was ultimately diagnosed with Mismatch Repair Cancer Syndrome-4, a subtype of Constitutional Mismatch Repair Deficiency syndrome. His newly discovered cancer predisposition syndrome led to multiple additional family members receiving the same diagnosis, which was especially important in a sibling with leukemia who received hematopoietic stem cell transplantation from an unaffected sibling donor.</div></div><div><h3>Conclusion</h3><div>While rare, cancer predisposition syndromes should be suspected in pediatric patients presenting with two or more synchronous, distinct cancer types.</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"296 ","pages":"Pages 205-207"},"PeriodicalIF":2.1,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144724598","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 : 2025-07-19DOI: 10.1016/j.cancergen.2025.07.011
Wei Li , Zishan Xu , Xiangyang Dong , Xiaoyu Yang , Gaoxiang Wang , Guoyang He
KRAS is the most frequently mutant human oncogene, with mutations present in more than 30% of colorectal cancer (CRC) cases. A rare somatic mutation in KRAS, NM_004985.5 : c.436G>A (p.Ala146Thr), was identified in carcinoma tissues from two CRC patients using Sanger sequencing. An alternative transcript of CDC37 was identified that retained intron 3. No splicing variant was detected within the coding exons and exon-intron boundaries of CDC37. The transcript encoded both truncated and full-length CDC37 proteins. Furthermore, KRAS, CDC37 and HSP90 interacted with each other. The expression levels of HSP90 and CDC37 in carcinoma tissues with the KRAS p.Ala146Thr mutation were higher than those in para-carcinoma tissues. Notably, the p.Ala146Thr mutation significantly upregulated the expression of CDK1, which in turn promoted CRC cell proliferation through activation of ERK signaling. These findings uncover a novel molecular mechanism underlying CRC pathogenesis associated with the KRAS p.Ala146Thr mutation and provide potential insights for developing targeted therapies for this subset of CRC.
{"title":"The KRAS p.Ala146Thr mutation promotes the proliferation of colorectal cancer cells via CDK1-mediated ERK signaling","authors":"Wei Li , Zishan Xu , Xiangyang Dong , Xiaoyu Yang , Gaoxiang Wang , Guoyang He","doi":"10.1016/j.cancergen.2025.07.011","DOIUrl":"10.1016/j.cancergen.2025.07.011","url":null,"abstract":"<div><div><em>KRAS</em> is the most frequently mutant human oncogene, with mutations present in more than 30% of colorectal cancer (CRC) cases. A rare somatic mutation in <em>KRAS</em>, NM_004985.5 : c.436G>A (p.Ala146Thr), was identified in carcinoma tissues from two CRC patients using Sanger sequencing. An alternative transcript of <em>CDC37</em> was identified that retained intron 3. No splicing variant was detected within the coding exons and exon-intron boundaries of <em>CDC37</em>. The transcript encoded both truncated and full-length CDC37 proteins. Furthermore, KRAS, CDC37 and HSP90 interacted with each other. The expression levels of HSP90 and CDC37 in carcinoma tissues with the <em>KRAS</em> p.Ala146Thr mutation were higher than those in para-carcinoma tissues. Notably, the p.Ala146Thr mutation significantly upregulated the expression of CDK1, which in turn promoted CRC cell proliferation through activation of ERK signaling. These findings uncover a novel molecular mechanism underlying CRC pathogenesis associated with the <em>KRAS</em> p.Ala146Thr mutation and provide potential insights for developing targeted therapies for this subset of CRC.</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"296 ","pages":"Pages 154-162"},"PeriodicalIF":1.4,"publicationDate":"2025-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144685460","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 : 2025-07-17DOI: 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}
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