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Identification of FUT7 hypomethylation as the blood biomarker in the prediction of early-stage lung cancer

遗传学报:英文版 2023年第8期50卷 573-581页

作者： Rong Qiao Feifei Di Jun Wang Yujie Wei Tian Xu Liping Dai Wanjian Gu Baohui Han rongxi yang Department of Pulmonary Medicine Shanghai Chest HospitalShanghai Jiaotong UniversityShanghai 200030China Nanjing TANTICA Biotechnology Co.Ltd NanjingJiangsu 210061China Department of Clinical Laboratory Jiangsu Province Hospital of Chinese MedicineNanjingJiangsu 210029China Henan Institute of Medical and Pharmaceutical Sciences Academy of Medical ScienceZhengzhou UniversityZhengzhouHenan 450001China Department of Epidemiology and Biostatistics School of Public HealthNanjing Medical UniversityNanjingJiangsu 211166China Department of Environmental Genomics Jiangsu Key Laboratory of Cancer BiomarkersPrevention and TreatmentCollaborative Innovation Center for Cancer Personalized MedicineNanjing Medical UniversityNanjingJiangsu 211166China Department of Genetic Toxicology The Key Laboratory of Modern Toxicology of Ministry of EducationCenter for Global HealthSchool of Public HealthNanjing Medical UniversityNanjingJiangsu 211166China

Early detection of lung cancer (LC) is vital for reducing LC-related mortality. However, noninvasive diagnostic tools remain a great challenge. We aim to identify blood-based biomarkers for the early detection of LC. Here, LC-associated hypomethylation in alpha-1,3-fucosyltransferase VII (FUT7) is identified via the Illumina 850K array in a discovery study and validated by mass spectrometry in two independent casecontrol studies with blood samples from 1720 LC patients (86.8% LC at stage I, blood is collected before surgery and treatment) and 3143 healthy controls. Compared to the controls, blood-based FUT7 hypomethylation is identified in LC patients at stage I, and even in LC patients with malignant nodules ≤1 cm and in patients with adenocarcinoma in situ. Gender plays a role in the LC-associated FUT7 hypomethylation in blood, which is more significant in males than in females. We also reveal that FUT7 hypomethylation in LC could be enhanced by the advanced stage of cancer, involvement of lymph nodes, and larger tumor size. Based on a large sample size and semi-quantitative methods, our study reveals a strong association between blood-based FUT7 hypomethylation and LC, suggesting that methylation signatures in blood may be a group of potential biomarkers for detection of early-stage LC.

关键词： Lung cancer Early detection DNA methylation FUT7 Mass spectrometry

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Comprehensive evaluation and spatial-temporal evolution characteristics of urban resilience in Chengdu-Chongqing Economic Circle

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Chinese Journal of Population,Resources and Environment 2024年第1期22卷 58-67页

作者： Xin Li Shuyi Zhang rongxi Ren Yafei Wang School of Economics and Management Chongqing Normal UniversityChongqing 401331China College of Marxism Taiyuan Normal UniversityTaiyuan 030619China Family Institute Northwestern UniversityChicago 60208USA

To clarify the connotations and extensions of urban resilience,this study focuses on the Chengdu-Chongqing Economic Circle with 16 cities as research subjects.A comprehensive evaluation index system was constructed to measure the resilience of each city from 2003 to *** spatial-temporal evolution characteristics were analyzed using Kernel density estimation,standard deviation ellipse,and spatial Markov chain analysis,and the spatial Tobit model was introduced to discover the influencing *** results indicate the following:①Urban resilience in the Chengdu-Chongqing Economic Circle displays an upward trend,with the center of gravity moving to the southwest,and the polarization phenomenon intensifying.②The urban resilience level in a region has certain spatial and geographical dependence,while the probability of urban resilience transfer differs in adjacent cities with different resilience levels.③Urban centrality,economic scale,openness level,and financial development promote urban resilience,whereas government scale significantly inhibits ***,this paper proposes countermeasures and suggestions to improve the urban resilience of the Chengdu-Chongqing Economic Circle.

关键词： Chengdu-chongqing Economic Circle Urban resilience Spatial-temporal evolution Driving factor

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东北三省人口流失的结构性与流向特征——基于长时序人口普查数据的区域比较分析

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地理科学 2024年第6期44卷 1016-1025页

作者：刘涛杨梦彭荣熙北京大学城市与环境学院/北京大学未来城市研究中心北京100871

利用1990—2020年历次全国人口普查和1%人口抽样调查数据,本文从结构和比较的视角考察了东北三省人口流失规模、来源和目的地选择的典型特征及动态变化。结果表明,东北三省人口流失是始于1990年的长期现象,但人口流失的规模和比例远低... 详细信息

利用1990—2020年历次全国人口普查和1%人口抽样调查数据,本文从结构和比较的视角考察了东北三省人口流失规模、来源和目的地选择的典型特征及动态变化。结果表明,东北三省人口流失是始于1990年的长期现象,但人口流失的规模和比例远低于中西部主要人口流出区;持续性的人口减少是人口流入率低、户籍迁出率高、城乡人口同步流出等多种原因造成的,也是东北人口流失的典型地域特征。经济因素是东北和其他省份外流人口目的地选择的共性主导因素;东北外流人口更加重视流入地的医疗卫生服务,近20 a的流出人口年轻化导致该地区对教育资源的偏好性大幅提升,且持续受到区位因素的较大制约,但始终没有明显的气候偏好性。区域吸引力不足的长期性和全面性意味着东北三省在尽力延缓人口流失趋势的同时,还应积极探索人口流失区高质量发展的新路径。

关键词：人口流失结构解析迁移空间选择区域比较研究东北地区

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数字技术驱动社区治理共同体建构:作用效果及限度——基于“全国社区治理和服务创新实验区”的实证研究

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甘肃行政学院学报 2024年第2期 56-65,126页

作者：杨秀勇张荣玺青岛大学政治与公共管理学院山东青岛266071 山东大学城市发展与公共政策研究所山东青岛266237

数字技术如何影响社区治理过程并驱动社区治理共同体构建,是推进基层治理现代化亟须明晰的重要问题。基于TOE分析框架,通过建构包括3个维度、9项观测指标和26条衡量指标的评估体系,对全国社区治理与服务创新实验区的14个典型案例进行实... 详细信息

数字技术如何影响社区治理过程并驱动社区治理共同体构建,是推进基层治理现代化亟须明晰的重要问题。基于TOE分析框架,通过建构包括3个维度、9项观测指标和26条衡量指标的评估体系,对全国社区治理与服务创新实验区的14个典型案例进行实证考察。研究发现,数字技术通过实现治理网络扁平化和开放性拓展、治理资源整合优化、治理价值重塑和社区治理制度再生产赋能社区治理共同体建设。同时,数字技术在驱动社区治理共同体建设过程中也存在社区治理主体智慧化理念缺失、主体结构与承接能力失衡、治理效果的内卷化、数据安全风险隐患等问题,成为社区治理共同体建设的阻滞因素。基于此,为更好发挥数字技术的赋能效果,规避其引致的负面效应,需要加快培育治理主体数字化理念,推动社区治理结构调整和能力升级,同时警惕技术治理的内卷行为和风险溢出问题。

关键词：数字技术社区治理共同体赋能机制 TOE框架

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Identification and Validation of HYAL1 DNA Methylation in Differentiating Malignant from Benign Thyroid Nodules

Identification and Validation of HYAL1 DNA Methylation in Di...

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2021年中国肿瘤标志物学术大会暨第十五届肿瘤标志物青年科学家论坛

作者： Mengxia Li Yin Yifei Li Hong yang rongxi 徐州医科大学附属淮安医院淮安市第二人民医院

Background: Thyroid cancer(TC) is the most common endocrine cancer around the world, of which papillary thyroid cancer(PTC) accounts for about 85%. Fine-needle aspiration biopsy(FNAB) is the preferred method for the diagnosis of thyroid nodules in the clinical application. However, about 20-30% of cases are indeterminate nodules according to FNAB, of which approximately 69% are classified as benign by postoperative pathology. Besides, the sensitivities of FNAB are 65-99% across studies. It is thus of great importance to develop novel biomarkers to distinguish the malignant tumors from the benign ones. DNA methylation is commonly dysregulated in a variety of diseases including cancers. Our previous Infinium Methylation EPIC 850 K beadchip assay indicated a differentially methylated CpG site(cg02183083) within hyaluronidase 1(HYAL1) gene. Here, we conducted a validation study to explore the association between HYAL1 and thyroid *** and methods: We measured the HYAL1 methylation level in formalin-fixed paraffin-embedded(FFPE) tissues of 195 early-stage PTC(91.05% PTC at stage Ⅰ) and 195 age-and gender-matched benign tumors collected during 2019-2020. The median(interquartile range, IQR) ages of malignant and benign cases were 51.00(44.00-57.00) and 53.00(46.00-60.25) years old, respectively. Females accounted for 78.95%(150/190) in both PTC and benign cases. Protein expression of HYAL1 was evaluated in another 55 pairs of early-stage PTC(89.09% PTC at stage Ⅰ) and benign tumors collected during 2013-2016, of which 34 pairs of cases were females. The median age was 43.00(31.00-51.00)and 47.00(36.00-52.00) years in PTC and benign *** methylation was quantified by matrixassisted laser desorption ionization time-of-flight mass spectrometry and protein expression was detected by immunohistochemical(IHC) staining. Binary logistic regression and Mann-Whitney U test were used for the data analysis. Two-sided P values < 0.05 were considered as statistically

关键词： Thyroid nodules HYAL1 Identification DNA methylation Protein

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Novel blood-based hypomethylation of DYRK4 is associated with very early stage lung cancer

Novel blood-based hypomethylation of DYRK4 is associated wit...

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2021年中国肿瘤标志物学术大会暨第十五届肿瘤标志物青年科学家论坛

作者： Chunlan Liu Qiang Zhu Qong Qiao Runbo Zhong rongxi yang Nanjing Medical University 上海交通大学附属上海胸科医院

Objective: Early detection is essential to improve the survival of lung cancer. The quantitative measurement of specific DNA methylation changes in the peripheral blood could provide an efficient strategy for the detection of early cancer. We applied a candidate approach and assess the association between blood-based DYRK4 methylation and the risk of lung cancer in a case-control ***: The methylation level of three CpG sites in the promoter of DYRK4 gene was quantitatively determined by mass spectrometry in 845 very early stage lung cancer patients(91.8% lung cancer at stage I) and 1000 healthy controls. The correlations between DNA methylation and the disease status were analyzed by binary logistic regression adjusted for possible co-founding effects of age, gender and different measurement batches. The comparisons between two or multiple groups were analyzed by non-parametric ***: All three investigated CpG sites in DYRK4 gene showed lower methylation levels in lung cancer cases than in control group(Figure 1 A-1 C), and decreased methylation of all these CpG loci showed significant association with lung cancer(odds ratio(ORs) per-10% methylation ranging from 1.17 to1.43, P<0.00017 for all, Figure 1 D). Interquartile analysis showed that compared to the quartile with the highest methylation level(Q4), the three lower quartiles of methylation levels(Q1-Q3) of all three CpG loci were highly associated with an increased risk of lung cancer, and this association was especially pronounced in the lowest quartile(P trend<0.001 for all, Figure 2). Further investigation disclosed that the hypomethylation of DYRK4 was associated with lung cancer with even larger ORs in the male group than that of the female group(OR per-10% methylation from 1.33 to1.66, P<0.000088 for all in males, Figure 3), which is in accordance with the fact the men have higher risk to lung cancer. The relationship between DYRK4 methylation and the clinical characteristics of845 lung

关键词： lung cancer DNA methylation DYRK4 gene early detection peripheral blood

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The association between MGRN1 methylation in peripheral blood and breast cancer in the Chinese population

The association between MGRN1 methylation in peripheral bloo...

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2021年中国肿瘤标志物学术大会暨第十五届肿瘤标志物青年科学家论坛

作者： Shuifang Lei Lixi Li Qiming Yin Yifei Yin Fei Ma rongxi yang Nanjing Medical University 国家癌症中心肿瘤内科徐州医科大学附属淮安医院淮安市第二人民医院甲状腺与乳腺外科

Aims: Mahogunin ring finger 1(MGRN1), an E3 ubiquitin ligase of the Really Interesting New Gene finger family, plays a pivotal role in many biological and cellular mechanisms. The DNA hypomethylation in MGRN1 has been reported to be associated with breast cancer(BC) in the Caucasian ***, the association has not been studied in other population. In this case-control study, we attempted to study the relationship between MGRN1 DNA methylation and BC in the Chinese *** and Methods: 4 MGRN1 CpG sites were quantitatively measured through mass spectrometry in the case-control study with 234 sporadic BC cases and 222 controls. The interquartile analysis was performed by calculating the quartiles from the methylation data from the total participants. The logistic regression adjusted for covariants and non-parametric tests were used to investigate the association between MGRN1 methylation level and the status of ***: We observed four MGRN1 CpG sites(MGRN1pG, MGRN1pG, MGRN1pG,4)were associated with BC. A significant tendency was also found for two MGRN1 CpG sites(P≤ 0.016,Table 1). In addition, we found significant associations between BC and altered MGRN1 methylation at different age groups, mostly in women at postmenopausal(age ≥ 50 years old, odds ratios(ORs)per-10% methylation: 1.58-1.85, P ≤ 0.031 for three of four CpG loci;age < 50 years old, ORs per-10% methylation = 0.77, P=0.033 for one CpG site, Table 2). This age-related MGRN1 methylation was also modified by the status of human epidermal growth factor receptor 2(HER2)(HER2 negative,ORs per-10% methylation: 0.86-1.28, P ≤ 0.045 for all four CpG loci;HER2 positive, ORs per-10%methylation = 0.79, P = 0.022 for one CpG site, Table 2).Conclusion: In the Chinese population, we reported a significant association between BC and the bloodbased MGRN1 methylation modified by age and the status of HER2. Above all, this study provided evidence of potential DNA methylation markers for early

关键词： Chinese population Breast cancer MGRN1 Methylation Blood

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大巴山陆内造山带高压古流体及其运移动力学机制研究

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地学前缘 2017年第2期24卷 123-129页

作者：覃小丽李荣西杨玲董树文何为杨清宇长安大学地球科学与资源学院陕西西安710054 国土资源部岩浆作用成矿与找矿重点实验室陕西西安710054 陕西省地质调查院陕西西安710065 中国地质科学院北京100037 中国石油长庆油田分公司勘探部陕西西安710021

陆内造山带普遍存在的高压流体与金属矿产与油气形成与分布关系十分密切。大巴山陆内造山带发育有大量同构造期方解石脉,碳氧同位素反映其为围岩碳酸盐岩成岩流体产物。通过对方解石脉中盐水包裹体分析测试,应用包裹体p-T-X相图确定的... 详细信息

陆内造山带普遍存在的高压流体与金属矿产与油气形成与分布关系十分密切。大巴山陆内造山带发育有大量同构造期方解石脉,碳氧同位素反映其为围岩碳酸盐岩成岩流体产物。通过对方解石脉中盐水包裹体分析测试,应用包裹体p-T-X相图确定的大巴山构造带同构造期古流体压力自北而南由高变低,即从大巴山逆冲构造带、大巴山前陆构造带到大巴山前陆坳陷古流体压力分别为240~270 MPa、220~240 MPa和170~190 MPa,而恢复的古流体压力梯度分别为2.2 MPa/100m、2.3 MPa/100m和2.0 MPa/100m,明显高于正常静水压力,表明大巴山陆内造山期古流体为典型异常高压流体。综合分析表明,大巴山陆内造山带和四川盆地自古至今普遍存在异常高压流体。结合区域地质研究认为,处于大巴山推覆体前缘、受志留系泥岩滑脱层和逆掩断层控制的高压体系具有压力封存箱特征。大巴山陆内造山带高压流体是在埋藏过程中形成的,其形成深度在2 800m左右,异常高压是大巴山构造带驱动流体迁移的主要动力之一。

关键词：方解石脉流体包裹体压力梯度陆内造山大巴山构造带

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外周血CCDC12基因甲基化在乳腺癌早期体外诊断中的价值

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中华医学杂志 2023年第44期103卷 3559-3566页

作者：郁文康羊晓勤黎立喜李俊杰张洁顾万建代丽萍马飞杨蓉西南京医科大学公共卫生学院流行病系，南京211166 四川大学华西医院乳腺外科，成都610041 国家癌症中心国家肿瘤临床医学研究中心中国医学科学院北京协和医学院肿瘤医院肿瘤内科，北京100021 江苏省中医院检验科，南京210029 郑州大学医学科学院河南医学与药学研究所，郑州450052

目的探究外周血CCDC12基因甲基化水平在乳腺癌早期诊断中的价值。方法采用接近1∶1配比的病例对照研究。收集中国医学科学院肿瘤医院、四川大学华西医院、郑州大学第一附属医院3个中心2018年4月至2022年12月乳腺癌患者和健康对照人群的... 详细信息

目的探究外周血CCDC12基因甲基化水平在乳腺癌早期诊断中的价值。方法采用接近1∶1配比的病例对照研究。收集中国医学科学院肿瘤医院、四川大学华西医院、郑州大学第一附属医院3个中心2018年4月至2022年12月乳腺癌患者和健康对照人群的外周血样本,采用飞行时间质谱法测定外周血CCDC12甲基化水平,通过logistic回归分析其与早期乳腺癌的相关性,非参数检验比较乳腺癌的各分子亚型和对照组的甲基化水平,受试者工作特征(ROC)曲线下面积评估该基因甲基化诊断乳腺癌的效能。结果最终纳入289例中位数年龄为50.0岁(42~56岁)的女性乳腺癌病例及320例中位数年龄为46.0岁(40~55岁)的健康女性对照。逻辑回归分析结果显示,CCDC12_CpG_6、CCDC12_CpG_7、CCDC12_CpG_10、CCDC12_CpG_11四个位点的高甲基化与乳腺癌密切相关(OR分别为1.26、1.18、1.20,P<0.02),按50岁年龄分层得到相似的结果;即使在早期乳腺癌中该基因的甲基化水平也显著升高(CCDC12_CpG_6、CCDC12_CpG_7、CCDC12_CpG_10、CCDC12_CpG_11,OR:1.16~1.21,P<0.05);与对照组相比,以上四个位点的甲基化水平在人表皮生长因子受体2(HER2)扩增型乳腺癌患者中显著升高(P<0.002)。结论CCDC12基因高甲基化与乳腺癌的发生密切相关,可作为乳腺癌早期诊断的一个指标。

关键词：乳腺肿瘤 DNA甲基化 CCDC12

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城市规划与产业规划的互动协同

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开放导报 2015年第1期 36-38页

作者：薛富智杨荣喜深圳市城市规划设计研究院广东深圳518028 台州市住房和城乡建设规划局浙江台州318000

城市规划和产业规划的协同是当前"多规统筹"实践中的重要内容,对于已经进入空间紧约束阶段的城市,城市和产业的协同问题变得更加复杂。应从政策机制到工作方法全面创新,以更加协调、有序、精准的空间和产业协同规划,实现二者更紧密的融... 详细信息

城市规划和产业规划的协同是当前"多规统筹"实践中的重要内容,对于已经进入空间紧约束阶段的城市,城市和产业的协同问题变得更加复杂。应从政策机制到工作方法全面创新,以更加协调、有序、精准的空间和产业协同规划,实现二者更紧密的融合,推动城市和经济可持续发展。

关键词：空间紧约束协同规划

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