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LncRNA DACH1 protects against pulmonary fibrosis by binding to SRSF1 to suppress CTNNB1 accumulation

Acta Pharmaceutica Sinica B 2022年第9期12卷 3602-3617页

作者： Jian Sun Tongzhu Jin Zhihui Niu Jiayu Guo Yingying Guo Ruoxuan Yang Qianqian Wang Huiying Gao Yuhan Zhang Tianyu Li Wenxin He Zhixin Li Wenchao Ma Wei Su Liangliang Li Xingxing Fan Hongli Shan Haihai Liang Department of Pharmacology(State-Province key Laboratories of Biomedicine-Pharmaceutics of China Key Laboratory of Cardiovascular ResearchMinistry of Education)College of PharmacyHarbin Medical UniversityHarbin 150081China Northern Translational Medicine Research and Cooperation Center Heilongjiang Academy of Medical SciencesHarbin Medical UniversityHarbin 150081China Department of thoracic Surgery Shanghai Pulmonary HospitalTongji UniversityShanghai 200433China State key laboratory of Quality Research in Chinese Medicine/Macao Institute for Applied Research in Medicine and Health Macao University of Science and TechnologyMacao(SAR)China Research Unit of Noninfectious Chronic Diseases in Frigid Zone(2019RU070) Chinese Academy of Medical SciencesHarbin 150081China Zhuhai People's Hospital Guangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and TreatmentZhuhai Hospital Affiliated with Jinan UniversityJinan UniversityZhuhai 519000China

Idiopathic pulmonary fibrosis(IPF)is a progressive disease with unknown etiology and limited therapeutic *** of fibroblasts is a prominent feature of pulmonary *** we report that lncRNA DACH1(dachshund homolog 1)is downregulated in the lungs of IPF patients and in an experimental mouse model of lung ***1 knockout mice develop spontaneous pulmonary fibrosis,whereas overexpression of LncDACH1 attenuated TGF-β1-induced aberrant activation,collagen deposition and differentiation of mouse lung ***,forced expression of LncDACH1 not only prevented bleomycin(BLM)-induced lung fibrosis,but also reversed established lung fibrosis in a BLM ***,LncDACH1 binding to the serine/arginine-rich splicing factor 1(SRSF1)protein decreases its activity and inhibits the accumulation of *** expression of SRSF1 blocked the anti-fibrotic effect of LncDACH1 in lung ***,loss of LncDACH1 promoted proliferation,differentiation,and extracellular matrix(ECM)deposition in mouse lung fibroblasts,whereas such effects were abolished by silencing of *** addition,a conserved fragment of LncDACH1 alleviated hyperproliferation,ECM deposition and differentiation of MRC-5 cells driven by TGF-β***,LncDACH1 inhibits lung fibrosis by interacting with SRSF1 to suppress CTNNB1 accumulation,suggesting that LncDACH1 might be a potential therapeutic target for pulmonary fibrosis.

关键词： Idiopathic pulmonary fibrosis LncRNA DACH1 SRSF1 CTNNB1 Fibroblast Myofibroblast Extracellular matrix Proliferation

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Efficacy and safety of anlotinib combined with the STUPP regimen in patients with newly diagnosed glioblastoma: a multicenter, single-arm, phase Ⅱ trial

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Cancer Biology & Medicine 2024年第5期21卷 433-444页

作者： Shuzhen Lai Peijing Li Xiaohui Liu Guihong Liu Tieming Xie Xing Zhang Xiaoxuan Wang Jing Huang Yiqiang Tang Zhigang Liu Guoping Shen Chaoming Li Fangxiao Lu Lei Wang Fagui Jiang Caixing Sun Yuanyuan Chen Ming Chen Department of Radiation oncology The Second Affiliated Hospital of Soochow UniversitySuzhou 215000China Department of Radiation oncology Yuebei People’s Hospital Affiliated to the Medical College of Shantou UniversityShaoguan 512026China Chinese Academy of SciencesHangzhou 310022China Department of Radiation oncology The Second Clinical Medical College of Zhejiang Chinese Medical UniversityHangzhou 311403China Department of Radiation oncology The Affiliated Hospital of Xuzhou Medical UniversityXuzhou 221004China Chinese Academy of SciencesHangzhou 310022China State key laboratory of Translational Medicine and Innovative Drug Development Jiangsu Simcere Diagnostics Co.LtdNanjing 210000China Department of Radiation oncology The Affiliated Huai’an First People’s Hospital of Nanjing Medical UniversityHuai’an 223399China Department of Radiation oncology Jiangxi Cancer Hospital of Nanchang UniversityNanchang 330029China Department of Radiotherapy Dongguan Institute of Clinical Cancer ResearchDongguan Key Laboratory of Precision Diagnosis and Treatment for TumorsAffiliated Dongguan HospitalSouthern Medical UniversityDongguan 523059China The Cancer Center The Fifth Affiliated Hospital of Sun Yat-Sen UniversityZhuhai 519000China Department of Radiation oncology The First Affiliated Hospital of Sun Yat-Sen UniversityGuangzhou 510080China Department of oncology Maoming People’s HospitalMaoming 525000China Department of Radiation oncology Kecheng District People’s HospitalQuzhou 324003China Chinese Academy of SciencesHangzhou 310022China Department of Radiation oncology State Key Laboratory of Oncology in South ChinaSun Yat-sen University Cancer CenterGuangzhou 510060China United laboratory of Frontier Radiotherapy technology of Sun Yat-sen University&Chinese Academy of Sciences Ion Medical technology Co. LtdGuangzhou 510060China

Objective:Glioblastomas are highly vascularized malignant *** determined the efficacy and safety of the anti-angiogenic multi-kinase inhibitor,anlotinib,for a newly diagnosed ***:This multicenter,single-arm trial(NCT04119674)enrolled 33 treatment-naïve patients with histologically proven glioblastomas between March 2019 and November *** underwent treatment with the standard STUPP regimen[fractionated focal irradiation in daily fractions of 1.8-2 Gy given 5 d/w×6 w(total=54-60 Gy)]or radiotherapy plus continuous daily temozolomide(TMZ)(75 mg/m^(2)of body surface area/d,7 d/w from the first to the last day of radiotherapy),followed by 6 cycles of adjuvant TMZ(150-200 mg/m^(2)×5 d during each 28-d cycle)plus anlotinib(8 mg/d on d 1-14 of each 3-w cycle for 2 cycles during concomitant chemoradiotherapy,8 maximal cycles as adjuvant therapy,followed by maintenance at 8 mg/*** primary endpoint was progression-free survival(PFS).Secondary endpoints included overall survival(OS)and adverse events(AEs).Results:Thirty-three patients received the planned *** median PFS was 10.9 months(95%CI,9.9-18.7 months)and the 12-month PFS rate was 48.5%.The median OS was 17.4 months(95%CI,14.5-21.1 months)and the 12-month OS rate was 81.8%.The most common AEs included hypertriglyceridemia[58%(n=19)],hypoalbuminemia[46%(n=15)],and hypercholesterolemia[46%(n=15)]during concurrent chemoradiotherapy and leukopenia[73%(n=24)],hypertriglyceridemia[67%(n=22)],and neutropenia[52%(n=17)]during adjuvant *** patients discontinued treatment due to ***1(HR,5.6;95%CI,1.3-23.7;P=0.021)and RP1L1 alterations(HR,11.1;95%CI,2.2-57.2;P=0.004)were associated with a significantly shorter ***:Anlotinib plus the STUPP regimen has promising anti-tumor activity against glioblastoma and manageable ***1 and RP1L1 alterations might be novel predictive biomarkers of the response to anlotinib.

关键词： Glioblastoma anti-angiogenesis multi-kinase inhibitor anlotinib temozolomide progression-free survival

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Multi-modality measurement and comprehensive analysis of hepatocellular carcinoma using synchrotron-based microscopy and spectroscopy

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Nuclear Science and Techniques 2021年第9期32卷 136-149页

作者： Gong-Xiang Wei Sui-Xia Zhang Zhao Li Fu-Li Wang Yan-Ling Xue Te Ji Hui-Qiang Liu School of Physics and Optoelectronic Engineering Shandong University of TechnologyZibo 255000China State key laboratory of Pathogenesis PreventionTreatment of Central Asian High Incidence DiseasesFirst Affiliated Hospital of Xinjiang Medical UniversityUrumqi 830054China oncology Department ZiBo Central HospitalZibo 255000China SSRF Shanghai Advanced Research InstituteChinese Academy of SciencesShanghai 201800China

The visualization and data mining of tumor multidimensional information may play a major role in the analysis of the growth,metastasis,and microenvironmental changes of tumors while challenging traditional imaging and data processing *** this study,a general trans-scale and multi-modality measurement method was developed for the quantitative diagnosis of hepatocellular carcinoma(HCC)using a combination of propagation-based phase-contrast computed tomography(PPCT),scanning transmission soft X-ray microscopy(STXM),and Fourier transform infrared micro-spectroscopy(FTIR).Our experimental results reveal the trans-scale micro-morpho-logical HCC pathology and facilitate quantitative data analysis and comprehensive *** results include some visualization features of PPCT-based tissue microenvironments,STXM-based cellular fine structures,and FTIR-based bio-macromolecular spectral characteris-tics during HCC tumor differentiation and *** proposed method provides multidimensional feature data support for constructing a high-accuracy machine learning algorithm based on a gray-level histogram,gray-gradient co-occurrence matrix,gray-level co-occurrence matrix,and back-propagation neural network ***-dimensional information analysis and diagnosis revealed the morphological pathways of HCC pathological evolution and we explored the relationships between HCC-related feature changes in inflammatory microenviron-ments,cellular metabolism,and the stretching vibration peaks of biomolecules of lipids,proteins,and nucleic ***,the proposed methodology has strong potential for the visualization of complex tumors and assessing the risks of tumor differentiation and metastasis.

关键词： Propagation based phase contrast tomography Soft X-ray microscopy Infrared micro spectroscopy Machine learning Tumor microenvironment and metastasis

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Epithelial-mesenchymal transition-related circular RNAs in lung carcinoma

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Cancer Biology & Medicine 2021年第2期18卷 411-420页

作者： Meina Jiang Shuai Fang Xiaodong Zhao Chengwei Zhou Zhaohui Gong Department of Biochemistry and Molecular Biology Ningbo University School of MedicineNingbo 315211China zhejiang Province key laboratory of Pathophysiology Ningbo University School of MedicineNingbo 315211China Department of thoracic Surgery The Affiliated Hospital of Ningbo University School of MedicineNingbo 315020China

The epithelial-mesenchymal transition(EMT)is a highly complex phenotypic conversion during embryogenesis,and is important for metastasis,which contributes to tumor deterioration and poor prognoses of cancer *** carcinoma has a high tendency to develop the *** RNAs(circ RNAs)are involved in EMT-related cell invasion and metastasis in various types of ***,circ RNAs have been found to be a link to EMT-related transcription factors and EMT-associated signaling *** review mainly focuses on the influence of EMT-related circ RNAs on lung *** specifically,the roles of EMT-inducingand EMT-suppressive circ RNAs in lung carcinomas are *** circ RNAs potentially becoming promising biomarkers and therapeutic targets for cancer managements,they will hopefully stimulate the interest of medical workers in the early diagnosis,personalized treatment,and positive prognoses in the era of precision oncology.

关键词： Epithelial-mesenchymal transition circular RNA transcription factor metastasis lung carcinoma

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Single-Cell Microwell Platform Reveals Circulating Neural Cells as a Clinical Indicator for Patients with Blood-Brain Barrier Breakdown

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Research 2021年第1期2021卷 1530-1542页

作者： Yu Zhang Antony R.Warden Khan Zara Ahmad Yanlei Liu Xijun He Minqiao Zheng Xinlong Huo Xiao Zhi Yuqing Ke Hongxia Li Sijia Yan Wenqiong Su Deng Cai Xianting Ding State key laboratory of Oncogenes and Related Genes Institute for Personalized MedicineSchool of Biomedical EngineeringShanghai Jiao Tong University1954 Huashan RoadShanghai 200030China Shanghai Engineering Research Centre for Intelligent diagnosis and treatment Instrument Department of Instrument Science and EngineeringSchool of Electronic Information and Electrical EngineeringShanghai Jiao Tong University800 Dongchuan RoadShanghai 200240China Department of Neurosurgery Wenling Hospital Affiliated to Wenzhou Medical UniversityChuan’an Nan RoadChengxi SubdistrictWenling317500 ZhejiangChina Central laboratory Wenling Hospital Affiliated to Wenzhou Medical UniversityChuan’an Nan RoadChengxi SubdistrictWenling317500 ZhejiangChina Department of Neurology Wenling Hospital Affiliated to Wenzhou Medical UniversityChuan’an Nan RoadChengxi SubdistrictWenling317500 ZhejiangChina Department of thoracic Surgery Shanghai Chest HospitalShanghai Jiao Tong University241 West Huaihai RoadShanghai 200030China

Central nervous system diseases commonly occur with the destruction of the blood-brain *** a primary cause of morbidity and mortality,stroke remains unpredictable and lacks cellular biomarkers that accurately quantify its occurrence and ***,we identify NeuN^(+)/CD45^(−)/DAPI^(+)phenotype nonblood cells in the peripheral blood of mice subjected to middle cerebral artery occlusion(MCAO)and stroke *** NeuN is a specific marker of neural cells,we term these newly identified cells as circulating neural cells(CNCs).We find that the enumeration of CNCs in the blood is significantly associated with the severity of brain damage in MCAO mice(p<0:05).Meanwhile,the number of CNCs is significantly higher in stroke patients than in negative subjects(p<0:0001).These findings suggest that the amount of CNCs in circulation may serve as a clinical indicator for the real-time prognosis and progression monitor of the occurrence and development of ischemic stroke and other nervous system disease.

关键词： Blood CD45 MCAO

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Development and validation of a nomogram for predicting the survival of patients with non-metastatic nasopharyngeal carcinoma after curative treatment

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Chinese Journal of Cancer 2016年第12期35卷 658-665页

作者： Wenhua Liang Guanzhu Shen Yaxiong Zhang Gang Chen Xuan Wu Yang Li Anchuan Li Shiyang Kang Xi Yuan Xue Hou Peiyu Huang Yan Huang Hongyun Zhao Ying Tian Chong Zhao Li Zhang State key laboratory of oncology in South China Collaborative Innovation Center for Cancer MedicineSun Yat-sen University Cancer Center Department of Medical oncology Sun Yat-sen University Cancer Center Department of thoracic Surgery/oncology The First Affiliated Hospital of Guangzhou Medical University Department of Radiation oncology Sun Yat-sen University Cancer Center Department of Radiotherapy Cancer Hospital of Guangzhou Medical University Department of Radiotherapy Sun Yat-sen University Cancer Center

Background: The TNM staging system is far from perfect in predicting the survival of individual cancer patients because only the gross anatomy is considered. The survival rates of the patients who have the same TNM stage disease vary across a wide spectrum. This study aimed to develop a nomogram that incorporates other clinicopathologic factors for predicting the overall survival(OS) of non-metastatic nasopharyngeal carcinoma(NPC) patients after curative ***: We retrospectively collected the clinical data of 1520 NPC patients who were diagnosed histologically between November 2000 and September 2003. The clinical data of a separate cohort of 464 patients who received intensity-modulated radiation therapy(IMRT) between 2001 and 2010 were also retrieved to examine the extensibility of the model. Cox regression analysis was used to identify the prognostic factors for building the nomogram. The predictive accuracy and discriminative ability were measured using the concordance index(c-index).Results: We identiied and incorporated 12 independent clinical factors into the nomogram. The calibration curves showed that the prediction of OS was in good agreement with the actual observation in the internal validation set and IMRT cohort. The c-index of the nomogram was statistically higher than that of the 7th edition TNM staging system for predicting the survival in both the primary cohort(0.69 vs. 0.62) and the IMRT cohort(0.67 vs. 0.63).Conclusion: We developed and validated a novel nomogram that outperformed the TNM staging system in predicting the OS of non-metastatic NPC patients who underwent curative therapy.

关键词： Nasopharyngeal carcinoma Nomogram Prognosis

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Management guidelines for primary lung cancer 2018: Chinese standards in clinical practice

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Chinese Journal of Cancer Research 2019年第3期31卷 419-420页

作者： Chao Lyu Nan Wu key laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing) Department of Thoracic Surgery II Peking University Cancer Hospital & Institute

Chinese guidelines for diagnosis and treatment of primary lung cancer 2018 are a set of clinical standards for screening, diagnosis and treatment of lung cancer in China (1). It covers the specialties of epidemiology, radiology, pathology, surgery, medical oncology, radiotherapy, endoscopy, nuclear medicine, and so on. The guidelines are referred to by physicians, medical students and patients, through providing comprehensive and detailed knowledge and recommendations in clinical practice on lung cancer diagnosis and treatment.

关键词： Chinese guidelines primary lung cancer diagnosis and treatment

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Clinical treatment considerationsin the intensity-modulated radiotherapy era for patients with NO-category nasopharyngeal carcinoma and enlarged neck lymph nodes

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Chinese Journal of Cancer 2017年第7期36卷 306-314页

作者： Hao Peng Lei Chen Rui Guo Yuan Zhang Wen.Fei Li Yan.Ping Mao Ying Sun Fan Zhang Li.Zhi Liu Li Tian Jun Ma State key laboratory of oncology in South China Collaborative Innovation Center for Cancer Medicine Sun Yat-sen University Cancer Center Guangzhou 510060 Guangdong P. R. China Department of Radiation oncology Sun Yat-sen University Cancer Center Guangzhou 510060 Guangdong P. R. China Imaging diagnosis and Interventional Center Sun Yat-sen University Cancer Center Guangzhou 510060 Guangdong P. R. China State key laboratory of oncology in South China Department of Radiation OncologySun Yat-sen University Cancer Center 651 Dongfeng Road East Guangzhou 510060 P. R. China

Background:Nasopharyngeal carcinoma(NPC) shows a high proportion of lymph node metastasis,and treatment guidelines have been developed for positive ***,no irradiation guidelines have been proposed for patients with enlarged neck lymph nodes(ENLNs) that do not meet the radiological criteria of 10 mm in diameter for positive lymph *** study aimed to determine the prognostic value and radiation dose for ENLNs in NO-category NPC patients treated with intensity-modulated radiotherapy(IMRT).Methods:We reviewed the medical data of 251 patients with non-metastatic,NO-category NPC treated with *** operating characteristic curves were used to calculate the cut-off value of the ENLN diameter for the prediction of disease *** biological equivalent dose(BED) for ENLNs was *** survival was compared between the small and large ENLN *** prognostic factors were identified using the Cox proportional hazards ***:The estimated 4-year regional relapse-free survival rate was higher in patients with ENLNs ≥5.5 mm than in those with ENLNs 0.05 for all survival rates).In the subgroup analysis,patients receiving BED ≥72 Gy had a similar prognosis as patients receiving BED <72 Gy in both the small and large ENLN *** multivariate analysis also confirmed that BED≥72 Gy was not associated with significantly improved prognosis in patients with NO-category ***:A BED of 72 Gy to ENLNs is considerably sufficient to provide a clinical benefit to patients with NO-category *** studies are warranted to validate the findings in the present study.

关键词： Nasopharyngeal carcinoma N0-category Enlarged neck lymph node Biological equivalent dose Intensity-modulated radiotherapy Prognosis

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Residual circulating tumor DNA after adjuvant chemotherapy effectively predicts recurrence of stage II-III gastric cancer

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Cancer Communications 2023年第12期43卷 1312-1325页

作者： Shu-Qiang Yuan Run-Cong Nie You-Sheng Huang Ying-Bo Chen Si-Yu Wang Xiao-Wei Sun Yuan-Fang Li Ze-Kun Liu Yan-Xing Chen Yi-Chen Yao Yu Xu Hai-Bo Qiu Yao Liang Wei Wang Ze-Xian Liu Qi Zhao Rui-Hua Xu Zhi-Wei Zhou Feng Wang Department of Gastric Surgery Sun Yat-sen University Cancer Center State key laboratory of oncology in South China Collaborative Innovation Center for Cancer Medicine Guangzhou Guangdong P. R. China Research Unit of Precision diagnosis and treatment for Gastrointestinal Cancer Chinese Academy of Medical Sciences Guangzhou Guangdong P. R. China Department of Medical oncology Sun Yat-sen University Cancer Center State key laboratory of oncology in South China Collaborative Innovation Center for Cancer Medicine Sun Yat-sen University Guangzhou Guangdong P. R. China Bioinformatics Platform Sun Yat-sen University Cancer Center Guangzhou Guangdong P. R. China

Background Circulating tumor DNA(ctDNA)is a promising biomarker for predicting relapse in multiple solid ***,the predictive value of ctDNA for disease recurrence remains indefinite in locoregional gastric cancer(GC).Here,we aimed to evaluate the predictive value of ctDNA in this *** From 2016 to 2019,100 patients with stage II/III resectable GC were recruited in this prospective cohort study(NCT02887612).Primary tumors were collected during surgical resection,and plasma samples were collected perioperatively and within 3 months after adjuvant chemotherapy(ACT).Somatic variants were captured via a targeted sequencing panel of 425 cancer-related *** plasma was defined as ctDNA-positive only if one or more variants detected in the plasma were presented in at least 2%of the primary *** Compared with ctDNA-negative patients,patients with positive postoperative ctDNA had moderately higher risk of recurrence[hazard ratio(HR)=2.74,95%confidence interval(CI)=1.37–5.48;P=0.003],while patients with positive post-ACT ctDNA showed remarkably higher risk(HR=14.99,95%CI=3.08-72.96;P<0.001).Multivariate analyses indicated that both postoperative and post-ACT ctDNA positivity were independent predictors of recurrence-free survival(RFS).Moreover,post-ACT ctDNA achieved better predictive performance(sensitivity,77.8%;specificity,90.6%)than both postoperative ctDNA and serial cancer antigen.A comprehensive model incorporating ctDNA for recurrence risk prediction showed a higher C-index(0.78;95%CI=0.71–0.84)than the model without ctDNA(0.71;95%CI=0.64–0.79;P=0.009).Conclusions Residual ctDNA after ACT effectively predicts high recurrence risk in stage II/III GC,and the combination of tissue-based and circulating tumor features could achieve better risk prediction.

关键词： gastric cancer ctDNA chemotherapy postoperative recurrence

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Lipid metabolism analysis in esophageal cancer and associated drug discovery

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Journal of Pharmaceutical Analysis 2024年第1期14卷 1-15页

作者： Ruidi Jiao Wei Jiang Kunpeng Xu Qian Luo Luhua Wang Chao Zhao Bionic Sensing and Intelligence Center Institute of Biomedical and Health EngineeringShenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhenGuangdong518000China Department of Radiation oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital&Shenzhen HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeShenzhenGuangdong518116China School of Medicine Southern University of Science and TechnologyShenzhenGuangdong518000China University of Chinese Academy of Sciences Beijing100049China Shenzhen key laboratory of Precision diagnosis and treatment of Depression Shenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhenGuangdong518000China

Esophageal cancer is an upper gastrointestinal malignancy with a bleak *** is still being explored in depth due to its complex molecular mechanisms of occurrence and *** play a crucial role in cells by participating in energy supply,biofilm formation,and signal transduction processes,and lipid metabolic reprogramming also constitutes a significant characteristic of malignant *** and more studies have found esophageal cancer has obvious lipid metabolism abnormalities throughout its beginning,progress,and treatment *** inhibition of tumor growth and the enhancement of antitumor therapy efficacy can be achieved through the regulation of lipid ***,we reviewed and analyzed the research results and latest findings for lipid metabolism and associated analysis techniques in esophageal cancer,and comprehensively proved the value of lipid metabolic reprogramming in the evolution and treatment resistance of esophageal cancer,as well as its significance in exploring potential therapeutic targets and biomarkers.

关键词： Lipid metabolism Esophageal cancer Progression treatment resistance New therapeutic targets

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