Carcinogenesis最新文献_第8页

Functional genetic variants of the disulfidptosis-related INF2 gene predict survival of hepatitis B virus-related hepatocellular carcinoma. 二硫化相关 INF2 基因的功能性遗传变异可预测乙型肝炎病毒相关肝细胞癌的存活率。

IF 4.7 3区医学

Carcinogenesis Pub Date : 2024-04-12 DOI: 10.1093/carcin/bgae003

Junjie Wei, Qiuping Wen, Shicheng Zhan, Ji Cao, Yanji Jiang, Jiawei Lian, Yuejiao Mai, Moqin Qiu, Yingchun Liu, Peiqin Chen, Qiuling Lin, Xiaoxia Wei, Yuying Wei, Qiongguang Huang, Ruoxin Zhang, Songqing He, Guandou Yuan, Qingyi Wei, Zihan Zhou, Hongping Yu

{"title":"Functional genetic variants of the disulfidptosis-related INF2 gene predict survival of hepatitis B virus-related hepatocellular carcinoma.","authors":"Junjie Wei, Qiuping Wen, Shicheng Zhan, Ji Cao, Yanji Jiang, Jiawei Lian, Yuejiao Mai, Moqin Qiu, Yingchun Liu, Peiqin Chen, Qiuling Lin, Xiaoxia Wei, Yuying Wei, Qiongguang Huang, Ruoxin Zhang, Songqing He, Guandou Yuan, Qingyi Wei, Zihan Zhou, Hongping Yu","doi":"10.1093/carcin/bgae003","DOIUrl":"10.1093/carcin/bgae003","url":null,"abstract":"Disulfidptosis is a novel form of programmed cell death involved in migration and invasion of cancer cells, but few studies investigated the roles of genetic variants in disulfidptosis-related genes in survival of patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). We used Cox proportional hazards regression analyses, Kaplan-Meier curves and receiver operating characteristic curves to assess effects of genetic variants in 14 disulfidptosis-related genes on overall survival of 866 HBV-HCC patients. The Bayesian false discovery probability was used for multiple testing corrections. We also investigated biological mechanisms of the significant variants through expression quantitative trait loci analyses using the data from publicly available databases, luciferase reporter assays and differential expression analyses. As a result, we identified two independently functional single nucleotide polymorphisms (SNPs) (INF2 rs4072285 G > A and INF2 rs4444271 A > T) that predicted overall survival of HBV-HCC patients, with adjusted hazard ratios of 1.60 (95% CI = 1.22-2.11, P = 0.001) and 1.50 (95% CI = 1.80-1.90, P < 0.001), respectively, after multiple testing correction. Luciferase reporter assays indicated that both INF2 rs4072285 A and INF2 rs4444271 T alleles increased INF2 mRNA expression levels (P < 0.001) that were also higher in HCC tumor tissues than in adjacent normal tissues (P < 0.001); such elevated INF2 expression levels were associated with a poorer survival of HBV-HCC patients (P < 0.001) in the TCGA database. In summary, this study supported that INF2 rs4072285 and INF2 rs4444271 may be novel biomarkers for survival of HBV-HCC patients.","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":null,"pages":null},"PeriodicalIF":4.7,"publicationDate":"2024-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139545760","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Sitravatinib combined with PD-1 blockade enhances cytotoxic T-cell infiltration by M2 to M1 tumor macrophage repolarization in esophageal adenocarcinoma. 西拉瓦替尼联合阻断PD1可增强食管癌中M2 - M1肿瘤巨噬细胞的细胞毒性t细胞浸润。

IF 4.7 3区医学

Carcinogenesis Pub Date : 2024-04-12 DOI: 10.1093/carcin/bgad087

Ryan Sweeney, Ashten N Omstead, John T Fitzpatrick, Ping Zheng, Anastasia Gorbunova, Erin E Grayhack, Arul Goel, Alisha F Khan, Juliann E Kosovec, Patrick L Wagner, Blair A Jobe, Ronan J Kelly, Ali H Zaidi

{"title":"Sitravatinib combined with PD-1 blockade enhances cytotoxic T-cell infiltration by M2 to M1 tumor macrophage repolarization in esophageal adenocarcinoma.","authors":"Ryan Sweeney, Ashten N Omstead, John T Fitzpatrick, Ping Zheng, Anastasia Gorbunova, Erin E Grayhack, Arul Goel, Alisha F Khan, Juliann E Kosovec, Patrick L Wagner, Blair A Jobe, Ronan J Kelly, Ali H Zaidi","doi":"10.1093/carcin/bgad087","DOIUrl":"10.1093/carcin/bgad087","url":null,"abstract":"Esophageal adenocarcinoma (EAC) is a leading cause of cancer-related mortality. Sitravatinib is a novel multi-gene tyrosine kinase inhibitor (TKI) that targets tumor-associated macrophage (TAM) receptors, VEGF, PDGF and c-Kit. Currently, sitravatinib is actively being studied in clinical trials across solid tumors and other TKIs have shown efficacy in combination with immune checkpoint inhibitors (ICI) in cancer models. In this study, we investigated the anti-tumor activity of sitravatinib alone and in combination with PD-1 blockade in an EAC rat model. Treatment response was evaluated by mortality, pre- and post-treatment MRI, gene expression, immunofluorescence and immunohistochemistry. Our results demonstrated adequate safety and significant tumor shrinkage in animals treated with sitravatinib, and more profoundly, sitravatinib and PD-1 inhibitor, AUNP-12 (P < 0.01). Suppression of TAM receptors resulted in increased gene expression of pro-inflammatory cytokines and decreased expression of anti-inflammatory cytokines, enhanced infiltration of CD8+ T cells, and M2 to M1 macrophage phenotype repolarization in the tumor microenvironment of treated animals (P < 0.01). Moreover, endpoint immunohistochemistry staining corroborated the anti-tumor activity by downregulation of Ki67 and upregulation of Caspase-3 in the treated animals. Additionally, pretreatment gene expression of TAM receptors and PD-L1 were significantly higher in major responders compared with the non-responders, in animals that received sitravatinib and AUNP-12 (P < 0.02), confirming that TAM suppression enhances the efficacy of PD-1 blockade. In conclusion, this study proposes a promising immunomodulatory strategy using a multi-gene TKI to overcome developed resistance to an ICI in EAC, establishing rationale for future clinical development.","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":null,"pages":null},"PeriodicalIF":4.7,"publicationDate":"2024-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138457987","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Actinomycin D synergizes with Doxorubicin in triple-negative breast cancer by inducing P53-dependent cell apoptosis. 放线菌素D与阿霉素协同作用诱导p53依赖性细胞凋亡治疗三阴性乳腺癌

IF 4.7 3区医学

Carcinogenesis Pub Date : 2024-04-12 DOI: 10.1093/carcin/bgad086

Hong Yang, Sha Li, Wan Li, Yihui Yang, Yizhi Zhang, Sen Zhang, Yue Hao, Wanxin Cao, Fang Xu, Hongquan Wang, Guanhua Du, Jinhua Wang

{"title":"Actinomycin D synergizes with Doxorubicin in triple-negative breast cancer by inducing P53-dependent cell apoptosis.","authors":"Hong Yang, Sha Li, Wan Li, Yihui Yang, Yizhi Zhang, Sen Zhang, Yue Hao, Wanxin Cao, Fang Xu, Hongquan Wang, Guanhua Du, Jinhua Wang","doi":"10.1093/carcin/bgad086","DOIUrl":"10.1093/carcin/bgad086","url":null,"abstract":"Objectives: There are three major subtypes of breast cancer, ER+, HER2+ and triple-negative breast cancer (TNBC), namely ER-, PR-, HER2-. TNBC is the most aggressive breast cancer with poor prognosis and no target drug up to now. Actinomycin D (ActD) is a bioactive metabolite of marine bacteria that has been reported to have antitumor activity. The aim of study is to investigate whether ActD has a synergetic effect on TNBC with Doxorubicin (Dox), the major chemotherapeutic drug for TNBC, and explore the underlying mechanism.Methods: TNBC cell lines HCC1937, MDA-MB-436 and nude mice were used in the study. Drug synergy determination, LDH assay, MMP assay, Hoechst 33342 staining, Flow cytometry, Flexible docking and CESTA assay were carried out. The expression of proteins associated with apoptosis was checked by Western blot and siRNA experiments were performed to investigate the role of P53 and PUMA induced by drugs.Results: There was much higher apoptosis rate of cells in the ActD + Dox group than that in ActD group or Dox group. Expression of MDM2 and BCL-2 was reduced while expression of P53, PUMA and BAX were increased in the groups treated with ActD + Dox or Dox compared to the control group. Furthermore, P53 siRNA or PUMA siRNA tremendously abrogated the cell apoptosis in the groups treated by ActD, Dox and ActD + Dox. Flexible docking and CESTA showed that ActD can bind MDM2.Conclusions: ActD had a synergetic effect on TNBC with Dox via P53-dependent apoptosis and it may be a new choice for treatment of TNBC.","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":null,"pages":null},"PeriodicalIF":4.7,"publicationDate":"2024-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138298480","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Surgical stress induced tumor immune suppressive environment. 手术应激诱导的肿瘤免疫抑制环境。

IF 4.7 3区医学

Carcinogenesis Pub Date : 2024-04-12 DOI: 10.1093/carcin/bgae012

Fan Yang, Qing Hua, Xiaoyan Zhu, Pingbo Xu

引用次数: 0

CRL4DCAF4 E3 ligase-mediated degradation of MEN1 transcriptionally reactivates hTERT to sustain immortalization in colorectal cancer cells. CRL4DCAF4 E3连接酶介导的MEN1转录降解可重新激活hTERT，从而维持结直肠癌细胞的永生化。

IF 4.7 3区医学

Carcinogenesis Pub Date : 2024-04-04 DOI: 10.1093/carcin/bgae024

Zhimin Ao, Dan Xiao, Jing Wu, Ji Sun, Hong Liu

{"title":"CRL4DCAF4 E3 ligase-mediated degradation of MEN1 transcriptionally reactivates hTERT to sustain immortalization in colorectal cancer cells.","authors":"Zhimin Ao, Dan Xiao, Jing Wu, Ji Sun, Hong Liu","doi":"10.1093/carcin/bgae024","DOIUrl":"https://doi.org/10.1093/carcin/bgae024","url":null,"abstract":"Telomerase reactivation is implicated in approximately 85% of human cancers, yet its underlying mechanism remains elusive. In this study, we elucidate that the Cullin RING Ubiquitin Ligase 4 (CRL4) complex drives the reactivation of human telomerase reverse transcriptase (hTERT) in colorectal cancer (CRC) by degrading the tumor suppressor, menin 1 (MEN1). Our data show that, in noncancerous intestinal epithelial cells, the transcription factor specificity protein 1 (Sp1) recruits both the histone acetyltransferase p300 and MEN1 to suppress hTERT expression, thus maintaining telomere shortness post-cell division. Inflammation-induced microenvironments trigger an activation of the CRL4DCAF4 E3 ligase, leading to MEN1 ubiquitination and degradation in CRC cells. This process nullifies MEN1's inhibitory action, reactivates hTERT expression at the transcriptional level, interrupts telomere shortening, and spurs uncontrolled cellular proliferation. Notably, MEN1 overexpression in CRC cells partially counteracts these oncogenic phenotypes. NSC1517, an inhibitor of the CRL4DCAF4 complex identified through high-throughput screening from a plant-derived chemical pool, hinders MEN1 degradation, attenuates hTERT expression, and suppresses tumor growth in mouse xenograft models. Collectively, our research elucidates the transcriptional mechanism driving hTERT reactivation in CRC. Targeting the CRL4DCAF4 E3 ligase emerges as a promising strategy to counteract cancer cell immortalization and curb tumor progression.","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":null,"pages":null},"PeriodicalIF":4.7,"publicationDate":"2024-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140744503","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Splicing factor ESRP1 derived circ_0068162 promotes the progression of oral squamous cell carcinoma via the miR-186/JAG axis. 剪接因子ESRP1衍生circ_0068162通过miR-186/JAG轴促进口腔鳞状细胞癌的进展。

IF 4.7 3区医学

Carcinogenesis Pub Date : 2024-03-11 DOI: 10.1093/carcin/bgad082

Shuai Chen, Yingrui Zong, Zhenzhen Hou, Zhifen Deng, Zongping Xia

{"title":"Splicing factor ESRP1 derived circ_0068162 promotes the progression of oral squamous cell carcinoma via the miR-186/JAG axis.","authors":"Shuai Chen, Yingrui Zong, Zhenzhen Hou, Zhifen Deng, Zongping Xia","doi":"10.1093/carcin/bgad082","DOIUrl":"10.1093/carcin/bgad082","url":null,"abstract":"Objectives: Oral squamous cell carcinoma (OSCC) is a common malignancy in the oral and maxillofacial regions with an increasing incidence rate. Circular RNA (circRNA) is a recently discovered long-chain non-coding RNA family member. The objective of this study was to analyze the role of circ_0068162 in OSCC development.Methods: We downloaded sample data GSE145608 from the Gene Expression Omnibus database. Online databases Starbase, TargetScan and miRDB were used to predict the target microRNAs (miRNAs) and genes. Cell viability and proliferation were assessed using the CCK-8 and EdU assays, respectively. Cell migration and invasion abilities were detected using transwell assay. The double luciferase reporter and RNA immunoprecipitation (RIP) assays were performed to verify the interaction relationship between the identified target molecules. RNase R and actinomycin D treatment were performed to analyze the stability of circ_0068162.Results: We found that circ_0068162 was overexpressed in the cytoplasm of OSCC cells and clinical OSCC tissues. Knockdown of circ_0068162 inhibited the growth, migration and invasion of OSCC cells. We also identified miR-186 as the target miRNA of circ_0068162, and JAG1 and JAG2 as the target genes of miR-186. The miR-186 inhibitor rescued the effects of sh-circ_0068162 and JAG1/JAG2 overexpression rescued the effects of miR-186 mimic in OSCC cells. Furthermore, ESRP1 promoted the biosynthesis of circ_0068162.Conclusions: The circ_0068162/miR-186/JAGs/ESRP1 feedback loop is closely related to OSCC development.","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":null,"pages":null},"PeriodicalIF":4.7,"publicationDate":"2024-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"107590305","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

A radiomics and genomics-derived model for predicting metastasis and prognosis in colorectal cancer. 用于预测结直肠癌转移和预后的放射组学和基因组学衍生模型

IF 4.7 3区医学

Carcinogenesis Pub Date : 2024-03-11 DOI: 10.1093/carcin/bgad098

Xue Li, Meng Wu, Min Wu, Jie Liu, Li Song, Jiasi Wang, Jun Zhou, Shilin Li, Hang Yang, Jun Zhang, Xinwu Cui, Zhenyu Liu, Fanxin Zeng

{"title":"A radiomics and genomics-derived model for predicting metastasis and prognosis in colorectal cancer.","authors":"Xue Li, Meng Wu, Min Wu, Jie Liu, Li Song, Jiasi Wang, Jun Zhou, Shilin Li, Hang Yang, Jun Zhang, Xinwu Cui, Zhenyu Liu, Fanxin Zeng","doi":"10.1093/carcin/bgad098","DOIUrl":"10.1093/carcin/bgad098","url":null,"abstract":"Approximately 50% of colorectal cancer (CRC) patients would develop metastasis with poor prognosis, therefore, it is necessary to effectively predict metastasis in clinical treatment. In this study, we aimed to establish a machine-learning model for predicting metastasis in CRC patients by considering radiomics and transcriptomics simultaneously. Here, 1023 patients with CRC from three centers were collected and divided into five queues (Dazhou Central Hospital n = 517, Nanchong Central Hospital n = 120 and the Cancer Genome Atlas (TCGA) n = 386). A total of 854 radiomics features were extracted from tumor lesions on CT images, and 217 differentially expressed genes were obtained from non-metastasis and metastasis tumor tissues using RNA sequencing. Based on radiotranscriptomic (RT) analysis, a novel RT model was developed and verified through genetic algorithms (GA). Interleukin (IL)-26, a biomarker in RT model, was verified for its biological function in CRC metastasis. Furthermore, 15 radiomics variables were screened through stepwise regression, which was highly correlated with the IL26 expression level. Finally, a radiomics model (RA) was established by combining GA and stepwise regression analysis with radiomics features. The RA model exhibited favorable discriminatory ability and accuracy for metastasis prediction in two independent verification cohorts. We designed multicenter, multi-scale cohorts to construct and verify novel combined radiomics and genomics models for predicting metastasis in CRC. Overall, RT model and RA model might help clinicians in directing personalized diagnosis and therapeutic regimen selection for patients with CRC.","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":null,"pages":null},"PeriodicalIF":4.7,"publicationDate":"2024-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139402013","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

IF 4.7 3区医学

Carcinogenesis Pub Date : 2024-03-11 DOI: 10.1093/carcin/bgad094

Yutaro Hori, Tomoaki Yoh, Hiroto Nishino, Keisuke Okura, Makoto Kurimoto, Yuichi Takamatsu, Motohiko Satoh, Takahiro Nishio, Yukinori Koyama, Takamichi Ishii, Keiko Iwaisako, Satoru Seo, Etsuro Hatano

{"title":"Ferroptosis-related gene glutathione peroxidase 4 promotes reprogramming of glucose metabolism via Akt-mTOR axis in intrahepatic cholangiocarcinoma.","authors":"Yutaro Hori, Tomoaki Yoh, Hiroto Nishino, Keisuke Okura, Makoto Kurimoto, Yuichi Takamatsu, Motohiko Satoh, Takahiro Nishio, Yukinori Koyama, Takamichi Ishii, Keiko Iwaisako, Satoru Seo, Etsuro Hatano","doi":"10.1093/carcin/bgad094","DOIUrl":"10.1093/carcin/bgad094","url":null,"abstract":"The role of the ferroptosis-related gene glutathione peroxidase 4 (GPX4) in oncology has been extensively investigated. However, the clinical implications of GPX4 in patients with intrahepatic cholangiocarcinoma (ICC) remain unknown. This study aimed to evaluate the prognostic impact of GPX4 and its underlying molecular mechanisms in patients with ICC. Fifty-seven patients who underwent surgical resection for ICC between 2010 and 2017 were retrospectively analyzed. Based on the immunohistochemistry, patients were divided into GPX4 high (n = 15) and low (n = 42) groups, and clinical outcomes were assessed. Furthermore, the roles of GPX4 in cell proliferation, migration and gene expression were analyzed in ICC cell lines in vitro and in vivo. The results from clinical study showed that GPX4 high group showed significant associations with high SUVmax on 18F-fluorodeoxyglucose-positron emission tomography (≥8.0, P = 0.017), multiple tumors (P = 0.004), and showed glucose transporter 1 (GLUT1) high expression with a trend toward significance (P = 0.053). Overall and recurrence-free survival in the GPX4 high expression group were significantly worse than those in the GPX4 low expression group (P = 0.038 and P < 0.001, respectively). In the experimental study, inhibition of GPX4 attenuated cell proliferation and migration in ICC cell lines. Inhibition of GPX4 also decreased the expression of glucose metabolism-related genes, such as GLUT1 or HIF1α. Mechanistically, these molecular changes are regulated in Akt-mechanistic targets of rapamycin axis. In conclusion, this study suggested the pivotal value of GPX4 serving as a prognostic marker for patients with ICC. Furthermore, GPX4 can mediate glucose metabolism of ICC.","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":null,"pages":null},"PeriodicalIF":4.7,"publicationDate":"2024-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138828319","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Retraction of: Pro-angiogenesis action of arsenic and its reversal by selenium-derived compounds. 撤回：砷的促血管生成作用及硒衍生化合物对其的逆转作用

IF 4.7 3区医学

Carcinogenesis Pub Date : 2024-03-11 DOI: 10.1093/carcin/bgad095

引用次数: 0

Human papillomavirus (HPV) DNA methylation changes in HPV-associated head and neck cancer. 人乳头瘤病毒（HPV）DNA甲基化在HPV相关头颈癌中的变化。

IF 4.7 3区医学

Carcinogenesis Pub Date : 2024-03-11 DOI: 10.1093/carcin/bgae001

Chameera Ekanayake Weeramange, Kai Dun Tang, Darryl Irwin, Gunter Hartel, Julian Langton-Lockton, Rahul Ladwa, Lizbeth Kenny, Touraj Taheri, Bernard Whitfield, Sarju Vasani, Chamindie Punyadeera

{"title":"Human papillomavirus (HPV) DNA methylation changes in HPV-associated head and neck cancer.","authors":"Chameera Ekanayake Weeramange, Kai Dun Tang, Darryl Irwin, Gunter Hartel, Julian Langton-Lockton, Rahul Ladwa, Lizbeth Kenny, Touraj Taheri, Bernard Whitfield, Sarju Vasani, Chamindie Punyadeera","doi":"10.1093/carcin/bgae001","DOIUrl":"10.1093/carcin/bgae001","url":null,"abstract":"Despite the rising incidence, currently, there are no early detection methods for HPV-driven HNC (HPV-HNC). Cervical cancer studies suggest that HPV DNA methylation changes can be used as a biomarker to discriminate cancer patients from HPV-infected individuals. As such, this study was designed to establish a protocol to evaluate DNA methylation changes in HPV late genes and long control region (LCR) in saliva samples of HPV-HNC patients and HPV-positive controls. Higher methylation levels were detected in HPV late genes (L1 and L2) in both tumour and saliva samples of HPV-HNC patients compared with HPV-positive controls. Moreover, methylation patterns between tumours and corresponding saliva samples were observed to have a strong correlation (Passing-Bablok regression analysis; τ = 0.7483, P < 0.0001). Considering the differences between HNC and controls in methylation levels in late genes, and considering primer amplification efficiencies, 13 CpG sites located at L1 and L2 genes were selected for further evaluation. A total of 18 HNC saliva samples and 10 control saliva samples were assessed for the methylation levels in the selected sites. From the CpG sites evaluated statistically significant differences were identified for CpG sites at L2-CpG 6 (P = 0.0004), L1-CpG 3 (P = 0.0144), L1-CpG 2 (P = 0.0395) and L2-CpG 19 (P = 0.0455). Our pilot data indicate that higher levels of DNA methylation in HPV late genes are indicative of HPV-HNC risk, and it is a potential supplementary biomarker for salivary HPV detection-based HPV-HNC screening.","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":null,"pages":null},"PeriodicalIF":4.7,"publicationDate":"2024-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10925951/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139545763","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0