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Exploring the potential of extrachromosomal DNA as a novel oncogenic driver

Science China Life Sciences 2025年第1期68卷 144-157页

作者： Huanbo Zhu Longtao Huangfu Junbing Chen Jiafu Ji Xiaofang Xing key laboratory of carcinogenesis and Translational Research (Ministry of Education/beijing) Division of Gastrointestinal Cancer Translational Research LaboratoryPeking University Cancer Hospital & Institute Department of Gastrointestinal cancer Center Peking University Cancer Hospital & Institute Department of Liver Surgery & Transplantation Liver Cancer InstituteZhongshan HospitalFudan University key laboratory of carcinogenesis and cancer Invasion Ministry of Education State key laboratory of Holistic Integrative Management of Gastrointestinal cancers Beijing Key Laboratory of Carcinogenesis and Translational ResearchDivision of Gastrointestinal Cancer Translational Research LaboratoryPeking University Cancer Hospital & Institute

Extrachromosomal DNA(ecDNA) is a form of circular DNA mostly found in tumor cells. Unlike the typical chromosomal DNA, ecDNA is circular, self-replicating, and carries complete or partial gene fragments. Although ecDNA occurrence remains a rare event in cancer, recent studies have shown that oncogene amplification on ecDNA is widespread throughout many types of cancer, implying that ecDNA plays a central role in accelerating tumor evolution. ecDNA has also been associated with increased tumor mutation burden, chromosomal instability, and even tumor microenvironment remodeling. ecDNA may be crucial in influencing tumor heterogeneity, drug sensitivity,oncogenic senescence, and tumor immunogenicity, leading to a worsening prognosis for tumor patients. In this way, several clinical trials have been conducted to investigate the importance of ecDNA in clinical treatment. In this review, we summarize the biogenesis, characteristics, and current research methods of ecDNA, discuss the vital role of ecDNA-caused tumor heterogeneity in cancers, and highlight the potential role of ecDNA in cancer therapy.

关键词： extrachromosomal DNA cancer therapy tumor heterogeneity drug resistance tumor evolution

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circT P63-N suppresses the proliferation and metastasis of nasopharyngeal carcinoma via engaging with HSP90AB1 to modulate the YAP1/Hippo signaling pathway

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Science China Life Sciences 2025年

作者： Dan Wang Sicheng Zuo Junshang Ge Hongke Qu Jie Wu Na Yi Lei Shi Yumin Wang Yongzhen Mo Chunmei Fan Yi He Pan Chen Ming Zhou Bo Xiang Wei Xiong Wenjia Guo Zhaoyang Zeng Can Guo NHC key laboratory of carcinogenesis and Hunan key laboratory of cancer Metabolism Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine Central South University key laboratory of carcinogenesis and cancer Invasion of the Chinese Ministry of Education Cancer Research Institute and School of Basic Medicine Sciences Central South University Furong laboratory cancer Research Institute Affiliated Cancer Hospital of Xinjiang Medical University Xinjiang key laboratory of Translational Biomedical Engineering

Circular RNAs(circRNAs) play pivotal roles in the development and progression of various diseases, including malignant tumors. However,the biological functions and the underlying mechanisms of many circRNAs remain elusive. In this study, we identified a novel circRNA,circTP63-N, generated through the splicing of exons 2–4 of the TP63 gene in nasopharyngeal carcinoma(NPC). circTP63-N was found to be downregulated in clinical samples of NPC. Both in vitro and in vivo experiments unequivocally demonstrated that circTP63-N inhibits the proliferation and metastasis of NPC cells. Further investigations revealed that circTP63-N interacted with the HSP90AB1 protein, leading to the recruitment of LATS/YAP1 proteins. This, in turn, induced phosphorylation and ubiquitination-dependent degradation of YAP1, resulting in reduced nuclear translocation of YAP1 and inhibition of the transcriptional activation of downstream oncogenic genes, including INHBA, MMP3, and CCNE2. Our findings highlight the identification of circTP63-N, a novel circRNA encoded by an important tumor-relevant gene TP63 and elucidate its molecular mechanism as a tumor suppressor in NPC. These insights offer novel potential molecular markers and therapeutic targets for the clinical diagnosis and treatment of NPC.

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Population-based cancer incidence analysis in beijing, 2008-2012

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Chinese Journal of cancer Research 2015年第1期27卷 13-21页

作者： Lei Yang Yannan Yuan Tingting Sun Huichao Li Ning Wang key laboratory of carcinogenesis and Translational Research (Ministry of Education) Beijing Office for Cancer Prevention and Control Peking University Cancer Hospital & Institute

Objective： To analyze the incidence of cancer during 2008-2012 in beijing, China, and compare the cancer spectrum with that during 1998-1999. Methods： Data from the beijing cancer Registry （BCR）, which covered 12 million residents and 16 administrative regions in beijing, were checked and evaluated on basis of the criteria of data quality from the National Central cancer Registry （NCCR） of China. Incidences were calculated stratified by cancer type, sex, areas （urban/rural）, and age. The Chinese census population in 1982 and the world Segi＇s population were used for calculating the age-standardized incidences. Results： A total of 177,101 new cancer cases were diagnosed in beijing between 2008 and 2012. The crude incidence rate （CR） of all cancers was 282.64/100,000 （290.71/100,000 in males and 274.45/100,000 in females）. The age-standardized rates by Chinese standard population （ASR-China） and by world standard population （ASR-world） were 124.46/100,000 and 161.18/100,000, respectivel）a Female breast cancer was the most common cancer, followed by lung cancer, colorectal cancer, liver cancer, and stomach cancer, with the CR of 59.87/100,000, 59.21/100,000, 32.49/100,000, 19.81/100,000 and 17.96/100,000, respectively. In urban areas, female breast cancer （68.50/100,000） was still the most common cancer, followed by lung cancer （61.23/100,000）, colorectal cancer （37.23/100,000）, prostate cancer （20.49/100,000） and stomach cancer （20.07/100,000）. In rural areas, lung cancer （55.94/100,000） was the most common cancer, followed by female breast cancer （45.87/100,000）, colorectal cancer （24.77/100,000）, liver cancer （20.68/100,000） and stomach cancer （14.52/100,000）. Great changes of the cancer spectrum were found from the period of 1998-1999 to the period of2011-2012 in beijing. Conclusions： The cancer burden in beijing was heavier than the national average level. cancer prevention and control strategies, especially for lung, colorectal, prostate and female thyroid cancer

关键词： cancer registry incidence epidemiology beijing

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Characteristics and trends in incidence of childhood cancer in beijing,China,2000-2009

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Chinese Journal of cancer Research 2014年第3期26卷 285-292页

Objective： To investigate the characteristics and incidence trends of childhood cancer in beijing, China, from 2000 to 2009. Methods： A total of 1,274 cases with childhood cancer in beijing from 2000 to 2009 were included in the study. All rates were age-standardized using the direct method to the world standard population and expressed per million person-years. Incidence trends were characterized by calculating annual percent change （APC） usingJoinpoint Regression Program. Results： The crude incidence rate was 106.47 per million [age-standardized rate （ASR） 113.34] between 2000 and 2009 in beijing with the most common diagnoses, leukemia （N=505, 39.64%, ASR 45.20）, followed by central nervous system （CNS） tumors （N=228, 17.90%, ASR 19.28） and lyrnphoma （N=91, 7.14%, ASR 6.97）. The incidence for all childhood cancers combined has increased during the study period, with an APC of 5.84% [95% confidence interval （95% CI）： 1.0-10.9] after adjusted by world population. The ASR of all combined cancers in boys showed a slight, but no significant increase, with an APC of 5.33 % （95 % CI： -0.6- 11.6）; for girls, the trends increased significantly, with an APC of 6.54% （95% CI： 1.5-11.8）. Conclusions： The incidence rate of childhood cancer in beijing was higher than the average level of China and lower than that of western countries. The incidence trends of childhood cancer, especially leukemia among girls showed a significantly increase from 2000 to 2009. While among boys, no substantially change was seen during the observed time period. Some sex-specific trends by subcategories and trends of major cancers in different age groups by cancer site merit further investigation.

关键词： Childhood cancer incidence epidemiology beijing

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cancer incidence in beijing, 2014

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Chinese Journal of cancer Research 2018年第1期30卷 13-20页

作者： Shuo Liu Lei Yang Yannan Yuan Huichao Li Jing Tian Sijia Lu Ning Wang Jiafu Ji key laboratory of carcinogenesis and Translational Research (Ministry of Education/beijing) Beijing Office for Cancer Prevention and ControlPeking University Cancer Hospital & Institute key laboratory of carcinogenesis and Translational Research (Ministry of Education/beijing) Center of Gastrointestinal Surgery Peking University Cancer Hospital & Institute

Objective： To analyze cancer incidence data in beijing in 2014 and temporal trends for selected common cancers during 2005 and ***： A total of 144 secondary and tertiary hospitals reported newly diagnosed cancer cases to beijing cancer Registry, which covers 13 million residents in beijing. The cancer incidence rate was calculated in strata by cancer type, sex, age group and area. The population composition of China in 1982 and Segi＇s population structure were used to calculate age-standardized rates. Extensive procedures were used to assure the quality of the ***： The overall data quality indicators of the percentage of morphology verification（MV）（%）, the percentage of death certificate-only（DCO）（%） and the mortality to incidence ratio（M/I） were 72.15%, 0.94% and0.54 respectively. A total of 45,300 new cancer cases were diagnosed in beijing in 2014. The incidence rate was341.92/100,000（343.50/100,000 in males, 340.33/100,000 in females）, and the age-standardized incidence rates by Chinese standard population（ASIRC） and by world standard population（ASIRW） were 143.48/100,000 and182.99/100,000, respectively. The cumulative incidence rate for cancer before 75 years was 20.61%. cancers of lung, colorectum, liver, stomach and prostate were the top five common cancer types for males, while cancers of breast, lung, thyroid, colorectum and uterus were the top five common cancer types for females. The different patterns were also observed between rural and urban areas. Regarding temporal trends, the incidence of thyroid cancer has the fastest growth between 2005 and 2014. The incidence of liver cancer decreased, and stomach and esophageal cancer also decreased significantly for males in the last decade. Incidence rate for lung cancer was relatively stable during that period of ***： With more than 45,000 new cases in beijing in 2014, cancer remains an important public health problem. Actions should be taken to diminish total cancer incidence in

关键词： cancer incidence epidemiology beijing

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Current Status of Diagnosis And Treatment of Primary Breast cancerin beijing,2008

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Chinese Journal of cancer Research 2011年第1期23卷 38-42页

作者： Xiao-mei Yuan Ning Wang Tao OuYang Lei Yang Ming-yang Song Ben-yao Lin Yun-tao Xie Jin-feng Li Kai-feng Pan Wei-cheng You Lian Zhang key laboratory of carcinogenesis and Translational Research （Ministry of Education） Department of Cancer EpidemiologyBeijing 100142 China key laboratory of carcinogenesis and Translational Research （Ministry of Education） Beijing Cancer RegistryBeijing 100142 China key laboratory of carcinogenesis and Translational Research （Ministry of Education） Breast Cancer Center Peking University School of OncologyBeijing Cancer Hospital ＆ Institute Beijing 100142 China

Objective：To investigate the status of diagnosis and treatment of primary breast cancer in beijing,***：All the patients who were diagnosed as primary breast cancer in beijing in 2008 were enrolled in this *** of these patients,including the features of tumors,clinical diagnosis and treatment was collected,and filled in the well-designed questionnaire forms by trained *** missing data were partly complemented through telephone ***：A total of 3473 beijing citizens were diagnosed as primary breast cancer（25 patients with synchronal bilateral breast cancer） in beijing,*** them 82.09% were symptomatic.19.02% and 34.11% were diagnosed using fine needle aspiration biopsy（FNAB） and core needle biopsy（CNB）,respectively.15.92% received sentinel lymph node biopsy（SLNB） and 24.27% received breast conserving surgery（BCS）.Among 476 cases with Her-2 positive,only 96 received anti-Her-2 *** found that the standardization level varied in hospitals of different grades,with higher level in Grade-III *** note,some breast cancer patients received non-standard primary tumor therapy：65.63% of the patients with ductal carcinoma in situ（DCIS） received axillary lymph node dissection and 36.88% received chemotherapy;25.89% of the patients underwent breast conserving surgery without margin status;12.10% of the patients received chemotherapy less than 4 ***：Although most breast cancer patients received basic medical care,the mode of diagnosis and treatment should be improved and should be standardized in the future in beijing.

关键词： Breast cancer Diagnosis Treatment Nonstandard treatment

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Polymorphism in the Hsa-miR-4274 seed region influences the expression of PEX5 and enhances radiotherapy resistance in colorectal cancer

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Frontiers of Medicine 2024年第5期18卷 921-937页

作者： Qixuan Lu Ningxin Ren Hongxia Chen Shaosen Zhang Ruoqing Yan Mengjie Li Linlin Zheng Wen Tan Dongxin Lin State key laboratory of Molecular Oncology Department of Etiology and CarcinogenesisBeijing Key Laboratory for Carcinogenesis and Cancer PreventionNational Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China Sun Yat-sen University cancer Center State Key Laboratory of Oncology in South ChinaGuangzhou 510060China

Identifying biomarkers for predicting radiotherapy efficacy is crucial for optimizing personalized *** previously reported that rs1553867776 in the miR-4274 seed region can predict survival in patients with rectal cancer receiving postoperative chemoradiation ***,to investigate the molecular mechanism of the genetic variation and its impact on the radiosensitivity of colorectal cancer(CRC),in this study,bioinformatics analysis is combined with functional experiments to confirm peroxisomal biogenesis factor 5(PEX5)as a direct target of *** miR-4274 rs1553867776 variant influences the binding of miR-4274 and PEX5 mRNA,which subsequently regulates PEX5 protein *** interaction between PEX5 and Ku70 was verified by co-immunoprecipitation and immunofluorescence.A xenograft tumor model was established to validate the effects of miR-4274 and PEX5 on CRC progression and radiosensitivity in *** overexpression of PEX5 enhances radiosensitivity by preventing Ku70 from entering the nucleus and reducing the repair of ionizing radiation(IR)-induced DNA damage by the Ku70/Ku80 complex in the *** addition,the enhanced expression of PEX5 is associated with increased IR-induced ***,targeting this mechanism might effectively increase the radiosensitivity of *** findings offer novel insights into the mechanism of cancer radioresistance and have important implications for clinical radiotherapy.

关键词： colorectal cancer polymorphism miR-4274 PEX5 radiotherapy resistance

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Time Trends of cancer Incidence in Urban beijing,1998-2007

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Chinese Journal of cancer Research 2011年第1期23卷 15-20页

作者： Ning Wang Wei-xing Zhu Xiu-mei Xing Lei Yang Ping-ping Li Wei-cheng You key laboratory of carcinogenesis and Translational Research （Ministry of Education） Beijing Cancer Registry Beijing 100142 China key laboratory of carcinogenesis and Translational Research （Ministry of Education） Department of Cancer Epidemiology Peking University School of Oncology Beijing Cancer Hospital ＆ Institute Beijing 100142 China

Objective：To report the time trends of cancer incidence in urban beijing from 1998 to ***：All data were obtained from beijing cancer Registry from 1998-2007 in urban *** trends of incidence rate of cancer were assessed by annual percentage change（APC） of age-standardized incidence rate（ASR） of world standard population during this 10-year ***：For all 156851 cancer cases combined,the incidence rate rose in both males and females,with an APC of 2.23% and 3.74%,*** incidence rate of upper gastrointestinal cancers declined significantly,with an APC of-2.83% in esophageal cancer and-1.37% in male gastric cancer,while lower gastrointestinal cancer,such as colorectal cancer,increased with an APC of 4.08%.The rates of kidney and bladder cancer increased with an APC of 7.93% and 5.57%,*** women,the APC continued to rise in breast cancer（4.98%）,ovary cancer（6.16%）,cervix uteri cancer（11.74%）,corpus uteri cancer（6.96%） and thyroid gland cancer（13.39%）.The rate of prostate cancer among men increased with an APC of 8.58%;the rate of lymphoma and leukemia increased with APC of 5.48% and 5.44%,***：Because of population aging and urban modernization,the cancer burden in beijing has become more and more severe and similar to the western developed countries.

关键词： Oncology Epidemiology Incidence Trend

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Kaiso mainly locates in the nucleus in vivo and binds to methylated,but not hydroxymethylated DNA

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Chinese Journal of cancer Research 2015年第2期27卷 148-155页

作者： Sisi Qin Baozhen Zhang Wei Tian Liankun Gu Zheming Lu Dajun Deng beijing key laboratory of carcinogenesis and Translational Research Division of Cancer EtiologyPeking University Cancer Hospital & Institute

Objective： Kaiso is upregulated in many cancers and proposed to bind with both methylated- and unmethylated-DNA in the nucleus as a transcriptional repressor. The objective is to define its subcellnlar localization in vivo and exact binding DNA sequences in cells. Methods： Compartmentalization of exogenous Kaiso in cells was tracked with enhanced green fluorescence protein （EGFP） tag. The endogenous Kaiso expression in gastric carcinoma tissue was examined with immunohistochemical staining. Kaiso-DNA binding was tested using electrophoretic mobility shift assay （EMSA） and chromatin immunoprecipitation assay （CHIP）. Results： Kaiso mainly localized in the nucleus of cancer and stromal cells in vivo, but remained in the cytoplasm of cultured cells. Most importantly, nuclear Kaiso can bind with the methylated-CGCG- containing sequence in the CDKN2A promoter, but not with the hydroxymethylated-CGCG sequence in HCT116 cells. Conclusions： Kaiso locates mainly in the nucleus in vivo where it binds with the methylated-CGCG sequences, but does not bind with the hydroxymethylated-CGCG sequences.

关键词： Kaiso compartmentalization DNA binding methylation hydroxymethylation CDKN2A

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Association between HER2 status and response to neoadjuvant anthracycline followed by paclitaxel plus carboplatin chemotherapy without trastuzumab in breast cancer

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Chinese Journal of cancer Research 2015年第6期27卷 553-561页

作者： Lu Yao Juan Zhang Yiqiang Liu Tao Ouyang Jinfeng Li Tianfeng Wang Zhaoqing Fan Tie Fan Benyao Lin Yuntao Xie key laboratory of carcinogenesis and Translational Research (Ministry of Education) Breast Center Beijing Cancer Hospital & Institute Peking University Cancer Hospital key laboratory of carcinogenesis and Translational Research (Ministry of Education) Department of Pathology Beijing Cancer Hospital & Institute Peking University Cancer Hospital

Background： We recently showed HER2-positive breast cancers are less likely to respond to neoadjuvant anthracycline chemotherapy. Here, we investigated whether HER2-positive breast cancers responded to sequential neoadjuvant anthracycline followed by paclitaxel plus carboplatin regimen in the absence of trastuzumab. Methods： Women （n=372） with operable primary breast cancer initially received two cycles of neoadjuvant anthracyclines, the clinical tumor response was assessed, then patients were received four cycles of paelitaxel plus carboplatin regimen. All the patients did not received trastuzumab treatment in the neoadjuvant setting. HER2 status was determined by immunohistochemistry and/or by fluorescence in situ hybridization in core- biopsy breast cancer tissue obtained before the neoadjuvant chemotherapy. Results： Eighteen percent （67/372） of patients achieved a pathologic complete response （pCR） in their breast. HER2-positive tumors had a significant higher pCR rate than HER2-negative tumors （33.0% versus 13.5%, P〈0.001） in this cohort of 372 patients, and positive HER2 status remained an independent favorable predictor of pCR in a multivariate analysis [odds ratio （OR）, 2.26; 95% confidence interval （CI）, 1.18 to 4.36, P=0.015]. Furthermore, patients who responded to initial anthracycline regimens were more likely to respond to paclitaxel plus carboplatin than patients who did not （pCR, 27.2% versus 14.6%, P=0.005）. Patients with HER2-positive tumors exhibited a significant higher pCR rate than did patients with HER2- negative tumors in both anthracycline response group （40.5% versus 20.0%, P=0.025） and anthracycline non-response group （28.3% versus 11.3 %, P=0.002）. Conclusions： Under the circumstance of no trastuzumab treatment, women with HER2-positive cancers derive a large benefit from paclitaxel-carboplatin-based neoadjuvant chemotherapy.

关键词： HER2 breast cancer neoadjuvant chemotherapy paclitaxel carboplatin

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