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Single-cell RNA-seq reveals the transcriptional program underlying tumor progression and metastasis in neuroblastoma

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Frontiers of Medicine 2024年第4期18卷 690-707页

作者： Zhe Nian Dan Wang Hao Wang Wenxu Liu Zhenyi Ma Jie Yan Yanna Cao Jie Li Qiang Zhao Zhe Liu Department of Immunology School of Basic Medical SciencesTianjin Medical UniversityTianjin300070China Zhejiang Key Laboratory of medical Epigenetics Department of Cell BiologySchool of Basic Medical SciencesHangzhou Normal UniversityHangzhou311121China Department of Pediatric Oncology Tianjin Medical University Cancer Institute and HospitalNational Clinical Research Center for CancerKey Laboratory of Cancer Prevention and TherapyTianjin’s Clinical Research Center for CancerTianjin300060China Collaborative Innovation center for cancer Personalized Medicine Nanjing Medical UniversityNanjing211166China

Neuroblastoma(NB)is one of the most common childhood *** percent of patients present with widely disseminated clinical signs at diagnosis and exhibit poor ***,the molecular mechanisms triggering NB metastasis remain largely *** this study,we generated a transcriptomic atlas of 15447 NB cells from eight NB samples,including paired samples of primary tumors and bone marrow *** used time-resolved analysis to chart the evolutionary trajectory of NB cells from the primary tumor to the metastases in the same patient and identified a common‘starter’subpopulation that initiates tumor development and ***‘starter’population exhibited high expression levels of multiple cell cycle-related genes,indicating the important role of cell cycle upregulation in NB tumor *** addition,our evolutionary trajectory analysis demonstrated the involvement of partial epithelial-to-mesenchymal transition(p-EMT)along the metastatic route from the primary site to the bone *** study provides insights into the program driving NB metastasis and presents a signature of metastasis-initiating cells as an independent prognostic indicator and potential therapeutic target to inhibit the initiation of NB metastasis.

关键词： single-cell RNA sequencing metastasis neuroblastoma epithelial-to-mesenchymal transition

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Epigenetics and environmental health

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Frontiers of Medicine 2024年第4期18卷 571-596页

作者： Min Zhang Ting Hu Tianyu Ma Wei Huang Yan Wang Key Laboratory of cancer and Microbiome State Key Laboratory of Molecular OncologyNational Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing100021China Beijing Key Laboratory of cancer Invasion and Metastasis Research Department of Biochemistry and Molecular BiologySchool of Basic Medical SciencesCapital Medical UniversityBeijing100069China

Epigenetic modifications including DNA methylation,histone modifications,chromatin remodeling,and RNA modifications complicate gene regulation and heredity and profoundly impact various physiological and pathological *** recent years,accumulating evidence indicates that epigenetics is vulnerable to environmental changes and regulates the growth,development,and diseases of individuals by affecting chromatin activity and regulating gene *** exposure or induced epigenetic changes can regulate the state of development and lead to developmental disorders,aging,cardiovascular disease,Alzheimer's disease,cancers,and so ***,epigenetic modifications are *** use of specific epigenetic inhibitors targeting epigenetic changes in response to environmental exposure is useful in disease ***,we provide an overview of the role of epigenetics in various ***,we summarize the mechanism of epigenetic alterations induced by different environmental exposures,the influence of different environmental exposures,and the crosstalk between environmental variation epigenetics,and genes that are implicated in the body's ***,the interaction of multiple factors and epigenetics in regulating the initiation and progression of various diseases complicates clinical *** discuss some commonly used epigenetic drugs targeting epigenetic modifications and methods to prevent or relieve various diseases regulated by environmental exposure and epigenetics through diet.

关键词： epigenetics environmental exposure health prevention and therapy

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The Largest Chinese Cohort Study Indicates Homologous Recombination Pathway Gene Mutations as Another Major Genetic Risk Factor for Colorectal cancer with Heterogeneous Clinical Phenotypes

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Research 2024年第3期6卷 191-203页

作者： Yun Xu Kai Liu Cong Li Minghan Li Fangqi Liu Xiaoyan Zhou Menghong Sun Megha Ranganathan Liying Zhang Sheng Wang Xin Hu Ye Xu Department of Colorectal Surgery Fudan University Shanghai Cancer CenterShanghaiP.R.China Department of Pathology Fudan University Shanghai Cancer CenterShanghaiP.R.China Department of Pathology Tissue BankFudan University Shanghai Cancer CenterShanghaiP.R.China Department of Medicine Memorial Sloan Kettering Cancer CenterNew YorkNYUSA Department of Pathology and Laboratory Medicine David Geffen School of MedicineUniversity of CaliforniaLos AngelesCAUSA Precision cancer medical center Fudan University Shanghai Cancer CenterShanghaiP.R.China

While genetic factors were associated with over 30% of colorectal cancer (CRC) patients, mutations in CRC-susceptibility genes were identified in only 5% to 10% of these patients. Besides, previous studies on hereditary CRC were largely designed to analyze germline mutations in patients with single genetic high-risk factor, which limited understanding of the association between genotype and phenotypes. From January 2015 to December 2018, we retrospectively enrolled 2,181 patients from 8,270 consecutive CRC cases, covering 5 categories of genetic high-risk factors. Leukocyte genomic DNA was analyzed for germline mutations in cancer predisposition genes. The germline mutations under each category were detected and analyzed in association with CRC susceptibility, clinical phenotypes, and prognoses. A total of 462 pathogenic variants were detected in 19.3% of enrolled CRC patients. Mismatch repair gene mutation was identified in 9.1% of patients, most prevalent across all high-risk groups. Homologous recombination (HR) gene mutations were detected in 6.5% of cases, penetrated in early-onset and extra-colonic cancer risk groups. Mutations in HR genes, including BARD1, RAD50, and ATM, were found to increase CRC risk with odds ratios of 2.8-, 3.1-, and 3.1-fold, respectively. CRC patients with distinct germline mutations manifested heterogeneous phenotypes in clinicopathology and long-term prognoses. Thus, germline mutation screenings should be performed for CRC patients with any of those genetic risk factors. This study also reveals that HR gene mutations may be another major driver for increased CRC risk.

关键词： susceptibility category Major

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Plant-based dietary patterns and risk of esophageal cancer:A prospective cohort study spanning 17 years

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Chinese Journal of cancer Research 2024年第1期36卷 36-45页

作者： Xiaorui Zhang Feifan He Jiayue Li Ru Chen Xinqing Li Li Li Fen Liu Shaoming Wang Wenqiang Wei Department of Epidemiology and Health Statistics School of Public HealthBeijing Municipal Key Laboratory of Clinical EpidemiologyCapital Medical UniversityBeijing 100069China National Central cancer Registry office National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China Department of cancer Epidemiology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China

Objective: Plant-based diets have multiple health benefits for cancers;however, little is known about the association between plant-based dietary patterns and esophageal cancer(EC).This study presents an investigation of the prospective associations among three predefined indices of plant-based dietary patterns and the risk of ***: We performed endoscopic screening for 15,709 participants aged 40-69 years from two high-risk areas of China from January 2005 to December 2009 and followed the cohort until December 31, 2022. The overall plant-based diet index(PDI), healthful plant-based diet index(h PDI), and unhealthful plant-based diet index(u PDI), were calculated using survey responses to assess dietary patterns. We applied Cox proportional hazard regression to estimate the multivariable hazard ratios(HRs) and 95% confidence intervals(95% CIs) of EC across 3plant-based diet indices and further stratified the analysis by ***: The final study sample included 15,184 participants in the cohort. During a follow-up of 219,365person-years, 176 patients with EC were identified. When the highest quartile was compared with the lowest quartile, the pooled multivariable-adjusted HR of EC was 0.50(95% CI, 0.32-0.77) for h PDI. In addition, the HR per 10-point increase in the h PDI score was 0.42(95% CI, 0.27-0.66) for ECs. Conversely, u PDI was positively associated with the risk of EC, and the HR was 1.80(95% CI, 1.16-2.82). The HR per 10-point increase in the u PDI score was 1.90(95% CI, 1.26-2.88) for ECs. The associations between these scores and the risk of EC were consistent in most subgroups. These results remained robust in sensitivity ***: A healthy plant-based dietary pattern was associated with a reduced risk of EC. Emphasizing the healthiness and quality of plant-based diets may be important for preventing the development of EC.

关键词： Esophageal cancer diet dietary pattern epidemiology nutrition prospective cohort study

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Network Pharmacology Based Elucidation of Molecular Mechanisms of Laoke Formula for Treatment of Advanced Non-Small Cell Lung cancer

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Chinese Journal of Integrative Medicine 2024年第11期30卷 984-992页

作者： FENG Yu-yu LIU Jin-feng XUE Yang LIU Dan WU Xiong-zhi Department of Nursing Tangshan Vocational and Technical College school of Chinese Materia Medica Tianjin University of Traditional Chinese Medicine Department of Oncology Tianjin Medical University General Hospital Tianjin medical university cancer Institute and Hospital National Clinical Research Center for Cancer Key Laboratory of Cancer Prevention and Therapy Tianjin's Clinical Research Center for China Tianjin Nankai Hospital Tianjin Medical University

Objective: To explore the specific pharmacological molecular mechanisms of Laoke Formula(LK)on treating advanced non-small cell lung cancer(NSCLC) based on clinical application, network pharmacology and experimental validation. Methods: Kaplan-Meier method and Cox regression analysis were used to evaluate the survival benefit of Chinese medicine(CM) treatment in 296 patients with NSCLC in Tianjin medical university cancer Institute and Hospital from January 2011 to December 2015. The compounds of LK were screened using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform, and the corresponding targets were performed from Swiss Target Prediction. NSCLC-related targets were obtained from Therapeutic Target Database and Comparative Toxicogenomics Database. Key compounds and targets were identified from the compound-target-disease network and protein-protein interaction(PPI) network analysis, respectively. Kyoto Encyclopedia of Genes and Genomes(KEGG) and Gene Ontology(GO) enrichment analysis were used to predict the potential signaling pathways involved in the treatment of advanced NSCLC with LK. The binding affinities between key ingredients and targets were further verified using molecular docking. Finally, A549 cell proliferation and migration assay were used to evaluate the antitumor activity of LK. Western blot was used to further verify the expression of key target proteins related to the predicted pathways. Results: Kaplan-Meier survival analysis showed that the overall survival of the CM group was longer than that of the non-CM group(36 months vs.26 months), and COX regression analysis showed that LK treatment was an independent favorable prognostic factor(P=0.027). Next, 97 components and 86 potential targets were included in the network pharmacology, KEGG and GO analyses, and the results indicated that LK was associated with proliferation and apoptosis. Moreover,molecular docking revealed a good binding affinity between the key

关键词： Chinese medicine LaoKe Formula anti-tumor network pharmacology non-small cell lung cancer

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Impact of metabolic dysfunction-associated steatotic liver disease on the efficacy of immunotherapy in patients with chronic hepatitis B-related hepatocellular carcinoma

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cancer Biology & Medicine 2024年第9期21卷 813-825页

作者： Jiaxin Han Wentao Kuai Liu Yang Xuemei Tao Yuekui Wang Minghui Zeng Yuqin Li Yuqiang Mi Ningning Zhang Wei Lu Liang Xu Clinical school of the Tianjin Second People's Hospital Tianjin Medical University Department of Hepatology Tianjin Second People's Hospital Tianjin Institute of Hepatology Department of Hepatobiliary Oncology Liver Cancer Center Tianjin Medical University Cancer Institute & Hospital National Clinical Research Center for Cancer Key Laboratory of Cancer Prevention and TherapyTianjin Tianjin's Clinical Research Center for Cancer

Objective: To investigate the impact of metabolic dysfunction-associated steatotic liver disease(MASLD) on the efficacy of immune checkpoint inhibitor(ICI)-based therapy in patients with chronic hepatitis B(CHB)-related hepatocellular carcinoma(HCC).Methods: A total of 155 patients with CHB-related HCC who received ICI±based therapy(in the Department of Hepatology, Tianjin Second People's Hospital and Department of Hepatobiliary Oncology, Tianjin medical university cancer Institute & Hospital) between April 2021 and December 2023 were *** were divided into two groups: MASLD concurrent with CHB [MASLD-CHB](n = 38), and CHB(n = 117).Results: The median progression-free survival(PFS, 6.9 months vs.9.3 months; P = 0.001), progressive disease(57.89% vs.37.61%; P = 0.028), and disease control rate(42.11% vs.62.39%; P = 0.028) in the MASLD-CHB group were significantly worse than the CHB *** median overall survival was not *** percentage of CD4+PD1+(17.56% vs.8.89%; P < 0.001) and CD8+PD1+ T cells(10.50% vs.7.42%; P = 0.005) in patient samples from the MASLD-CHB group were significantly higher than the CHB *** MASLD [hazard ratio(HR) = 1.921; 95% CI, 1.138±3.245; P = 0.015] and alpha-fetoprotein levels after 3 months of treatment(HR = 2.412; 95% CI, 1.360±4.279; P = 0.003) were independent risk factors for PFS in all ***: ICI-based therapy in patients with CHB-related HCC and concurrent MASLD resulted in poorer efficacy and shorter PFS compared to patients with CHB-related HCC alone.

关键词： Metabolic dysfunction-associated steatotic liver disease chronic hepatitis B efficacy hepatocellular carcinoma immunotherapy

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Modeling human gastric cancers in immunocompetent mice

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cancer Biology & Medicine 2024年第7期21卷 553-570页

作者： Weihong Zhang Shilong Wang Hui Zhang Yan Meng Shi Jiao Liwei An Zhaocai Zhou Department of Stomatology Department of Medical UltrasoundShanghai Tenth People's HospitalTongji University Cancer CenterTongji University School of MedicineShanghai 200072China State Key Laboratory of Genetic Engineering School of Life SciencesZhongshan HospitalFudan UniversityShanghai 200032China Collaborative Innovation center for cancer Personalized Medicine School of Public HealthNanjing Medical UniversityNanjing 211166China

Gastric cancer(GC)is a major cause of cancer-related mortality *** is determined by multiple(epi)genetic and environmental factors;can occur at distinct anatomic positions of the stomach;and displays high heterogeneity,with different cellular origins and diverse histological and molecular *** heterogeneity has hindered efforts to fully understand the pathology of GC and develop efficient *** the past decade,great progress has been made in the study of GC,particularly in molecular subtyping,investigation of the immune microenvironment,and defining the evolutionary path and *** mouse models,particularly immunocompetent models that mimic the cellular and molecular features of human GC,in combination with organoid culture and clinical studies,have provided powerful tools for elucidating the molecular and cellular mechanisms underlying GC pathology and immune evasion,and the development of novel therapeutic ***,we first briefly introduce current progress and challenges in GC study and subsequently summarize immunocompetent GC mouse models,emphasizing the potential application of genetically engineered mouse models in antitumor immunity and immunotherapy studies.

关键词： Gastric cancer heterogeneity mouse model GEMM immunocompetent

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Treatment patterns and survival outcomes in patients with nonmetastatic early-onset pancreatic cancer

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World Journal of Gastroenterology 2024年第12期30卷 1739-1750页

作者： Le-Tian Zhang Ying Zhang Bi-Yang Cao Chen-Chen Wu Jing Wang Graduate school Chinese PLA Medical SchoolBeijing 100853China Department of Radiation Oncology First Medical Center of Chinese PLA General HospitalBeijing 100853China Department of Internal Medicine Hospital of University of Science and Technology BeijingBeijing 100083China Department of medical Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China

BACKGROUND The incidence of patients with early-onset pancreatic cancer(EOPC;age≤50 years at diagnosis)is on the rise,placing a heavy burden on individuals,families,and *** role of combination therapy including surgery,radiotherapy,and chemotherapy in non-metastatic EOPC is not *** To investigate the treatment patterns and survival outcomes in patients with non-metastatic *** A total of 277 patients with non-metastatic EOPC who were treated at our institution between 2017 and 2021 were investigated *** survival(OS),disease-free survival,and progression-free survival were estimated using the Kaplan-Meier *** and multivariate analyses with the Cox proportional hazards model were used to identify prognostic *** With a median follow-up time of 34.6 months,the 1-year,2-year,and 3-year OS rates for the entire cohort were 84.3%,51.5%,and 27.6%,*** median OS of patients with localized disease who received surgery alone and adjuvant therapy(AT)were 21.2 months and 28.8 months,respectively(P=0.007).The median OS of patients with locally advanced disease who received radiotherapy-based combination therapy(RCT),surgery after neoadjuvant therapy(NAT),and chemotherapy were 28.5 months,25.6 months,and 14.0 months,respectively(P=0.002).The median OS after regional recurrence were 16.0 months,13.4 months,and 8.9 months in the RCT,chemotherapy,and supportive therapy groups,respectively(P=0.035).Multivariate analysis demonstrated that carbohydrate antigen 19-9 level,pathological grade,T-stage,N-stage,and resection were independent prognostic factors for non-metastatic *** AT improves postoperative survival in localized *** after NAT and RCT are the preferred therapeutic options for patients with locally advanced EOPC.

关键词： Pancreatic cancer Early-onset Non-metastatic Multimodal treatment Radiotherapy Overall survival

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Pan-cancer immunogenic death analysis identifies key roles of CXCR3 and CCL18 in hepatocellular carcinoma

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Genes & Diseases 2024年第2期11卷 568-570页

作者： Jia Guo Xin Sun Guowei Pan Ce Li Xin He Xiaofang Che Zan Teng Xiujuan Qu Yunpeng Liu Bowen Yang Department of medical Oncology Provincial Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning ProvinceLiaoning Provincial Clinical Research Center for CancerClinical Cancer Research Center of ShenyangThe First Hospital of China Medical UniversityShenyangLiaoning 110001China Research center for Universal Health School of Public HealthChina Medical UniversityShenyangLiaoning 110122China

Immunogenic death is a form of programmed cell death that is common in the development and progression of ***,its impact on tumor progression differs depending on the location of the ***,it also plays an important role in antitumor immunity because the process of immunogenic death can release substances that activate immunity.1 Therefore,in this study,the key mechanism of mediating immunogenic death in hepatocellular carcinoma(HCC)was found from the excavation of the immunogenic death characteristics of pan-cancer and the in-depth investigation of its effects on different tumor types(Fig.1A).

关键词： death CXCR3 immunity

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Chemoselective labeling-based spermatozoa glycan imaging reveals abnormal glycosylation in oligoasthenotspermia

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Chinese Chemical Letters 2024年第4期35卷 475-480页

作者： Lijia Xu Tong Zhong Wei Zhao Bing Yao Lin Ding Huangxian Ju State Key Laboratory of Analytical Chemistry for Life Science School of Chemistry and Chemical EngineeringNanjing UniversityNanjing 210023China Department of Reproductive medical center Jinling HospitalSchool of MedicineNanjing UniversityNanjing 210002China Chemistry and Biomedicine Innovation center(ChemBIC) Nanjing UniversityNanjing 210023China center of Clinical Laboratory Science The Affiliated Cancer Hospital of Nanjing Medical University&Jiangsu Cancer Hospital&Jiangsu Institute of Cancer ResearchNanjing 210009China

Spermatogenesis, maturation, capacitation and fertilization are precisely regulated by glycosylation. However, the relationship between altered glycosylation patterns and the onset and development of reproductive disorders is unclear, mainly limited by the lack of in situ imaging techniques for spermatozoa glycosylation. We developed an efficient and highly specific spermatozoa glycan imaging technique based on the robust chemoselective labeling of sialic acid(Sia) and N-acetyl-D-galactosamine(Gal/GalNAc). We further proposed a “tandem glycan chemoselective labeling” strategy to achieve simultaneous imaging of two types of glycans on spermatozoa. We applied the developed method to the spermatozoa from oligozoospermic patients and diabetic mice and found that these spermatozoa showed higher levels of Sia and Gal/Gal NAc expression than the normal groups. Moreover, spermatozoa from diabetic mice showed a severe decrease in number, viability, and forward motility, suggesting that in vivo glucose metabolism disorders may lead to an elevated level of spermatozoa glycosylation and have a correlation with the development of oligoasthenotspermia. Our work provides a research tool to reveal the relationship between glycosylation modification and spermatozoa quality, and a promising clue for the development of glycan-based reproductive markers.

关键词： Spermatozoa Glycan Chemoselective labeling Oligoasthenotspermia Fluorescence imaging

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