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The activity and immune dynamics of PD-1 inhibition on high-risk pulmonary ground glass opacity lesions:insights from a single-arm,phase II trial

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Signal Transduction and Targeted Therapy 2024年第5期9卷 2202-2214页

作者： Bo Cheng Caichen Li Jianfu Li Longlong Gong Peng Liang Ying Chen Shuting Zhan Shan Xiong Ran Zhong Hengrui Liang Yi Feng Runchen Wang Haixuan Wang Hongbo Zheng Jun Liu Chengzhi Zhou Wenlong Shao Yuan Qiu Jiancong Sun Zhanhong Xie Zhu Liang Chenglin Yang Xiuyu Cai Chunxia Su Wei Wang Jianxing He Wenhua Liang department of Thoracic Surgery and oncology the First Affiliated Hospital of Guangzhou Medical UniversityGuangzhou Institute of Respiratory HealthState Key Laboratory of Respiratory DiseaseNational Clinical Research Center for Respiratory DiseaseGuangzhouChina Medical department Genecast Biotechnology Co.LtdWuxiChina department of radiation oncology the First Affiliated Hospital of Guangzhou Medical UniversityGuangzhouChina department of Respiratory Medicine the First Affiliated Hospital of Guangzhou Medical UniversityGuangzhou Institute of Respiratory HealthState Key Laboratory of Respiratory DiseaseNational Clinical Research Center for Respiratory DiseaseGuangzhouChina department of Cardiothoracic Surgery Affiliated Hospital of Guangdong Medical UniversityZhanjiangChina department of Thoracic Surgery National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital&Shenzhen HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeShenzhenChina department of VIP Inpatient Sun Yat-sen University Cancer CenterState Key Laboratory of Oncology in South ChinaSun Yat-sen UniversityGuangzhouChina department of Medical oncology Shanghai Pulmonary HospitalSchool of MedicineTongji UniversityShanghaiChina

Immune checkpoint inhibitors targeting the programmed cell death-1(PD-1)protein significantly improve survival in patients with advanced non-small-cell lung cancer(NSCLC),but its impact on early-stage ground-glass opacity(GGO)lesions remains unclear.This is a single-arm,phase II trial(NCT04026841)using Simon’s optimal two-stage design,of which 4 doses of sintilimab(200 mg per 3 weeks)were administrated in 36 enrolled multiple primary lung cancer(MPLC)patients with persistent high-risk(Lung-RADS category 4 or had progressed within 6 months)GGOs.The primary endpoint was objective response rate(ORR).T/B/NK-cell subpopulations,TCR-seq,cytokines,exosomal RNA,and multiplexed immunohistochemistry(mIHC)were monitored and compared between responders and non-responders.Finally,two intent-to-treat(ITT)lesions(pure-GGO or GGO-predominant)showed responses(ORR:5.6%,2/36),and no patients had progressive disease(PD).No grade 3-5 TRAEs occurred.The total response rate considering two ITT lesions and three non-intent-to-treat(NITT)lesions(pure-solid or solid-predominant)was 13.9%(5/36).The proportion of CD8^(+)T cells,the ratio of CD8^(+)/CD4^(+),and the TCR clonality value were significantly higher in the peripheral blood of responders before treatment and decreased over time.Correspondingly,the mIHC analysis showed more CD8^(+)T cells infiltrated in responders.Besides,responders’cytokine concentrations of EGF and CTLA-4 increased during treatment.The exosomal expression of fatty acid metabolism and oxidative phosphorylation gene signatures were down-regulated among responders.Collectively,PD-1 inhibitor showed certain activity on high-risk pulmonary GGO lesions without safety concerns.Such effects were associated with specific T-cell re-distribution,EGF/CTLA-4 cytokine compensation,and regulation of metabolism pathways.

关键词： lesions metabolism doses

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Consensus of Chinese experts on glioma multidisciplinary team management (2nd edition)

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中华医学杂志(英文版) 2024年第11期137卷 1267-1270页

作者： Wu Jinsong Zhou Zhirui Wu Zanyi Tang Zhiwei Li Ming Yin Siyuan Luo Xufei Wang Ling Chen Yaolong Zhao Guoguang Jiang Tao Mao Ying The National Glioma MDT Alliance of National Center for Neurological Diseases department of Neurosurgery Beijing Tiantan Hospital Capital Medical University Beijing China department of Neurosurgery Huashan Hospital Shanghai Medical College Fudan University Shanghai China department of radiation oncology Huashan Hospital Shanghai Medical College Fudan University Shanghai China department of Neurosurgery The First Affiliated Hospital of Fujian Medical University Fuzhou Fujian China Neurosurgery department The First Affiliated Hospital of Kunming Medical University Kunming Yunnan China department of Neurosurgery Henan Provincial People’s Hospital People’s Hospital of Zhengzhou University Zhengzhou Henan China State Key Laboratory of pharmaceutical biotechnology Institute for Brain Sciences Advanced Institute for Life Sciences School of Life Sciences Nanjing University Nanjing Jiangsu China Evidence-Based Medicine Center School of Basic Medical Sciences Lanzhou University Lanzhou Gansu China School of Public Health Lanzhou University Lanzhou Gansu China department of Neurosurgery Xuanwu Hospital Capital Medical University Beijing China

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GLUL stabilizes N-Cadherin by antagonizing β-Catenin to inhibit the progresses of gastric cancer

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Acta Pharmaceutica Sinica B 2024年第2期14卷 698-711页

作者： Qiwei Jiang Yong Li Songwang Cai Xingyuan Shi Yang Yang Zihao Xing Zhenjie He Shengte Wang Yubin Su Meiwan Chen Zhesheng Chen Zhi Shi department of Cell Biology&institute of Biomedicine National Engineering Research Center of Genetic MedicineState Key Laboratory of Bioactive Molecules and Druggability AssessmentMOE Key Laboratory of Tumor Molecular BiologyGuangdong Provincial Key Laboratory of Bioengineering MedicineCollege of Life Science and TechnologyJinan UniversityGuangzhou 510632China department of Gastrointestinal Surgery&General Surgery the Guangdong Provincial People’s HospitalGuangdong Academy of Medical SciencesGuangzhou 510080China department of Thoracic Surgery The First Affiliated Hospital of Jinan UniversityGuangzhou 510632China department of radiation oncology The Fifth Hospital of Guangzhou Medical UniversityGuangzhou 510150China State Key Laboratory of Quality Research in Chinese Medicine Institute of Chinese Medical SciencesUniversity of MacaoMacao 519000China department of pharmaceutical Sciences College of Pharmacy and Health SciencesSt.John’s UniversityQueensNY 11439USA

Glutamate-ammonia ligase(GLUL, also known as glutamine synthetase) is a crucial enzyme that catalyzes ammonium and glutamate into glutamine in the ATP-dependent condensation. Although GLUL plays a critical role in multiple cancers, the expression and function of GLUL in gastric cancer remain unclear. In the present study, we have found that the expression level of GLUL was significantly lower in gastric cancer tissues compared with adjacent normal tissues, and correlated with N stage and TNM stage, and low GLUL expression predicted poor survival for gastric cancer patients. Knockdown of GLUL promoted the growth, migration, invasion and metastasis of gastric cancer cells in vitro and in vivo, and vice versa, which was independent of its enzyme activity. Mechanistically, GLUL competed with β-Catenin to bind to N-Cadherin, increased the stability of N-Cadherin and decreased the stability of β-Catenin by alerting their ubiquitination. Furthermore, there were lower N-Cadherin and higher β-Catenin expression levels in gastric cancer tissues compared with adjacent normal tissues. GLUL protein expression was correlated with that of N-Cadherin, and could be the independent prognostic factor in gastric cancer. Our findings reveal that GLUL stabilizes N-Cadherin by antagonizing β-Catenin to inhibit the progress of gastric cancer.

关键词： Gastric cancer GLUL N-Cadherin β-Catenin Enzyme

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Effects of traditional Chinese medicine on treatment outcomes in severe COVID-19 patients:a single-centre study

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Chinese Journal of Natural Medicines 2024年第1期22卷 89-96页

作者： XIAO Yongjiu LI Binbin LIU Chang HUANG Xiuyu MA Ling QIAN Zhirong ZHANG Xiaopeng ZHANG Qian LI Dunqing CAI Xiaoqing YAN Xiangyong LUO Shuping XIANG Dawei XIAO Kun Emergency department the 940th Hospital of Jiont Logistics Support Force of Chinese People’s Liberation ArmyLanzhou 730050China Scientific Research Center the Seventh Affiliated HospitalSun Yat-sen UniversityShenzhen 518000China School of Medicine Nankai universityTianjin 300000China department of Cardiology the 940th Hospital of Joint Logistics Support Force of Chinese People’s Liberation ArmyLanzhou 730050China department of radiation oncology Fujian Medical University Union HospitalFuzhou 350000China department of Traditional Chinese Medicine the 940th Hospital of Joint Logistics Support Force of Chinese People’s Liberation ArmyLanzhou 730050China department of Geriatric Diseases the Seventh Medical Center of Chinese PLA General HospitalBeijing 100700China Health and Sport Administration Muskingum UniversityOhioanUSA Laboratory of Vaccine and Antibody Engineering Beijing Institute of BiotechnologyBeijing 100071China department of Pulmonary and Critical Care Medicine the 940th Hospital of Joint Logistics Support Force of Chinese People’s Liberation ArmyLanzhou 730050China Center of Pulmonary&Critical Care Medicine Chinese People’s Liberation Army(PLA)General HospitalBeijing 100853China

As the search for effective treatments for COVID-19 continues,the high mortality rate among critically ill patients in Intensive Care Units(ICU)presents a profound challenge.This study explores the potential benefits of traditional Chinese medicine(TCM)as a supplementary treatment for severe COVID-19.A total of 110 critically ill COVID-19 patients at the Intensive Care Unit(ICU)of Vulcan Hill hospital between Feb.,2020,and April,2020(Wuhan,China)participated in this observational study.All patients received standard supportive care protocols,with a subset of 81 also receiving TCM as an adjunct treatment.Clinical characteristics during the treatment period and the clinical outcome of each patient were closely monitored and analysed.Our findings indicated that the TCM group exhibited a significantly lower mortality rate compared with the non-TCM group(16 of 81 vs 24 of 29;0.3 vs 2.3 person/month).In the adjusted Cox proportional hazards models,TCM treatment was associated with improved survival odds(P<0.001).Furthermore,the analysis also revealed that TCM treatment could partially mitigate inflammatory responses,as evidenced by the reduced levels of proinflammatory cytokines,and contribute to the recovery of multiple organic functions,thereby potentially increasing the survival rate of critically ill COVID-19 patients.

关键词： COVID-19 Pneumonia Novel coronavirus Critically ill Traditional Chinese medicine Clinical outcome

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Pharmacological inhibition of BAP1 recruits HERC2 to competitively dissociate BRCA1-BARD1, suppresses DNA repair and sensitizes CRC to radiotherapy

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Acta Pharmaceutica Sinica B 2023年第8期13卷 3382-3399页

作者： Xin Yue Tingyu Liu Xuecen Wang Weijian Wu Gesi Wen Yang Yi Jiaxin Wu Ziyang Wang Weixiang Zhan Ruirui Wu Yuan Meng Zhirui Cao Liyuan Le Wenyan Qiu Xiaoyue Zhang Zhenyu Li Yong Chen Guohui Wan Xianzhang Bu Zhenwei Peng Ran-yi Liu State Key Laboratory of oncology in South China Sun Yat-sen University Cancer CenterGuangzhou 510060China department of radiation oncology the First Affiliated HospitalSun Yat-sen UniversityGuangzhou 510080China School of pharmaceutical Sciences Sun Yat-sen UniversityGuangzhou 510006China department of Clinical Research Guangzhou Institute of Respiratory Healththe First Affiliated Hospital of Guangzhou Medical UniversityGuangzhou 510120China department of Gastrointestinal Surgery the First Affiliated HospitalSun Yat-sen UniversityGuangzhou 510080China department of oncology the Sixth Affiliated HospitalSun Yat-sen UniversityGuangzhou 510655China department of Traditional Chinese Medicine the First Affiliated HospitalSun Yat-sen UniversityGuangzhou 510080China Zhongshan School of Medicine Sun Yat-sen UniversityGuangzhou 510080China Laboratory of Chemical Oncogenomics Guangdong Provincial Key Laboratory of Chemical GenomicsPeking University Shenzhen Graduate SchoolShenzhen 518055China

Radiotherapy is widely used in the management of advanced colorectal cancer(CRC).However,the clinical efficacy is limited by the safe irradiated dose.Sensitizing tumor cells to radiotherapy via interrupting DNA repair is a promising approach to conquering the limitation.The BRCA1-BARD1 complex has been demonstrated to play a critical role in homologous recombination(HR)DSB repair,and its functions may be affected by HERC2 or BAP1.Accumulated evidence illustrates that the ubiquitination-deubiquitination balance is involved in these processes;however,the precise mechanism for the cross-talk among these proteins in HR repair following radiation hasn’t been defined.Through activity-based profiling,we identified PT33 as an active entity for HR repair suppression.Subsequently,we revealed that BAP1 serves as a novel molecular target of PT33 via a CRISPR-based deubiquitinase screen.Mechanistically,pharmacological covalent inhibition of BAP1 with PT33 recruits HERC2 to compete with BARD1 for BRCA1 interaction,interrupting HR repair.Consequently,PT33 treatment can substantially enhance the sensitivity of CRC cells to radiotherapy in vitro and in vivo.Overall,these findings provide a mechanistic basis for PT33-induced HR suppression and may guide an effective strategy to improve therapeutic gain.

关键词： Pharmacological inhibition BAP1 HERC2recruitment BRCA1 BARD1 Competitively dissociation HR-Mediated DNArepair,CRCradiosensitization

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Microwave triggered multifunctional nanoplatform for targeted photothermal-chemotherapy in castration-resistant prostate cancer

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Nano Research 2023年第7期16卷 9688-9700页

作者： Pengyuan Liu Yajun Wu Xiaogang Xu Xudong Fan Chuan Sun Xiaojie Chen Jindan Xia Shiting Bai Li Qu Huasong Lu Jing Wu Jun Chen Ji-Gang Piao Zhibing Wu department of oncology Affiliated Zhejiang HospitalZhejiang University School of MedicineHangzhou 310013China School of pharmaceutical Sciences Zhejiang Chinese Medical UniversityHangzhou 310053China department of radiation oncology Affiliated Zhejiang HospitalZhejiang University School of MedicineHangzhou 310013China Geriatrics institute of Zhejiang Province Department of GeriatricsAffiliated Zhejiang HospitalZhejiang University School of MedicineHangzhou 310030China Zhejiang Provincial Key Laboratory for Cancer Molecular Cell Biology Life Sciences InstituteZhejiang UniversityHangzhou 310058China TCM Dispensary Affiliated Zhejiang HospitalZhejiang University School of MedicineHangzhou 310013China department of Breast Surgery Affiliated Hangzhou First People’s HospitalZhejiang University School of MedicineHangzhou 310006China

Lacking a precise targeting strategy,castration-resistant prostate cancer(CRPC)is still hard to be treat effectively.Exploring treatment options that can accurately target CPRC is an important issue with urgent need.In this study,a novel nanotechnologybased strategy had been developed for the precise target treatment of CRPC.By combining microwaves and photothermal therapy(PTT),this nanoplatform,cmHSP70-PL-AuNC-DOX,targets tumor tissues with outstanding precision and achieves better anti-tumor activity by simultaneously eliciting photothermal and chemotherapeutic effects.From nanotechnology,cmHSP70-modified and thermo-sensitive liposome-coated AuNC-DOX were prepared and used for CRPC-targeted photothermal ablation and chemotherapy.Doxorubicin(DOX)was selected as the chemotherapeutic agent for cytotoxicity.In terms of the curative scheme,prostate tissues were firstly pre-treated with microwaves to induce the expression of heat shock protein 70(HSP70)and its migration to the cell membrane,which was then targeted by HSP70 antibody(cmHSP70)coated on the nanoparticles to achieve accurate drug delivery.The nanoplatform then achieved precise ablation and controlled release of DOX under external near-infrared(NIR)irradiation.Through the implementation,the targeting,cell killing,and safety of this therapeutical strategy had been verified in vivo and in vitro.This work establishes an accurate,controllable,efficient,non-invasive,and safe treatment platform for targeting CRPC,provides a rational design for CRPC’s PTT,and offers new prospects for nanomedicines with great precision.

关键词： castration-resistant prostate cancer gold nanocage heat shock protein 70 targeted drug delivery photothermalchemotherapy

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Detection and quantitative analysis of tumor-associated tertiary lymphoid structures

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Journal of Zhejiang University-Science B(Biomedicine & biotechnology) 2023年第9期24卷 779-795页

作者： Man YANG Yurou CHE Kezhen LI Zengyi FANG Simin LI Mei WANG Yiyao ZHANG Zhu XU Liping LUO Chuan WU Xin LAI Weidong WANG department of radiation oncology Radiation Oncology Key Laboratory of Sichuan ProvinceSichuan Clinical Research Center for CancerSichuan Cancer Hospital&InstituteAffiliated Cancer Hospital of University of Electronic Science and Technology of ChinaChengdu610000China School of Medicine University of Electronic Science and Technology of ChinaChengdu610000China department of oncology School of Clinical MedicineSouthwest Medical UniversityLuzhou646000China

Tumor-associated tertiary lymphoid structures(TLSs)are ectopic lymphoid formations within tumor tissue,with mainly B and T cell populations forming the organic aggregates.The presence of TLSs in tumors has been strongly associated with patient responsiveness to immunotherapy regimens and improving tumor prognosis.Researchers have been motivated to actively explore TLSs due to their bright clinical application prospects.Various studies have attempted to decipher TLSs regarding their formation mechanism,structural composition,induction generation,predictive markers,and clinical utilization.Meanwhile,the scientific approaches to qualitative and quantitative descriptions are crucial for TLS studies.In terms of detection,hematoxylin and eosin(H&E),multiplex immunohistochemistry(mIHC),multiplex immunofluorescence(mIF),and 12-chemokine gene signature have been the top approved methods.However,no standard methods exist for the quantitative analysis of TLSs,such as absolute TLS count,analysis of TLS constituent cells,structural features,TLS spatial location,density,and maturity.This study reviews the latest research progress on TLS detection and quantification,proposes new directions for TLS assessment,and addresses issues for the quantitative application of TLSs in the clinic.

关键词： Tertiary lymphoid structure Tumor microenvironment Chemokine signature Spatial omics Artificial intelligence Radiomics

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Paclitaxel liposome for injection (Lipusu) plus cisplatin versus gemcitabine plus cisplatin in the first-line treatment of locally advanced or metastatic lung squamous cell carcinoma: A multicenter, randomized, open-label, parallel controlled clinical study

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Cancer Communications 2022年第1期42卷 3-16页

作者： Jie Zhang Yueyin Pan Qin Shi Guojun Zhang Liyan Jiang Xiaorong Dong Kangsheng Gu Huijuan Wang Xiaochun Zhang Nong Yang Yuping Li Jianping Xiong Tienan Yi Min Peng Yong Song Yun Fan Jiuwei Cui Gongyan Chen Wei Tan Aimin Zang Qisen Guo Guangqiang Zhao Ziping Wang Jianxing He Wenxiu Yao Xiaohong Wu Kai Chen Xiaohua Hu Chunhong Hu Lu Yue Da Jiang Guangfa Wang Junfeng Liu Guohua Yu Junling Li Jianling Bai Wenmin Xie Weihong Zhao Lihong Wu Caicun Zhou department of Medical oncology Shanghai Pulmonary Hospital&Thoracic Cancer InstituteTongji University School of MedicineShanghai 200433P.R.China department of Chemotherapy Anhui Provincial HospitalHefeiAnhui 230001P.R.China department of oncology Fuzhou Pulmonary Hospital of FujianFuzhouFujian 350008P.R.China department of Respiratory Medicine the First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenan 450052P.R.China department of Respiration Shanghai Chest HospitalShanghai Jiao Tong UniversityShanghai 200030P.R.China Cancer Center Union Hospital of Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei 430022P.R.China department of Medical oncology the First Affiliated Hospital of Anhui Medical UniversityHefeiAnhui 230032P.R.China department of Respiration Henan Cancer HospitalZhengzhouHenan 450008P.R.China department of Medical oncology the Affiliated Hospital of Qingdao UniversityQingdaoShandong 266000P.R.China department of Medical oncology Hunan Cancer HospitalChangshaHunan 410013P.R.China department of Pulmonary and Critical Care Medicine the First Affiliated Hospital of Wenzhou Medical CollegeShangcai villageWenzhouZhejiang 325000P.R.China department of Medical oncology the First Affiliated Hospital of Nanchang UniversityNanchangJiangxi 330006P.R.China department of Medical oncology Xiang Yang Central HospitalXiangyangHubei 441021P.R.China department of Medical oncology Renmin Hospital of Wuhan UniversityWuhanHubei 430060P.R.China department of Respiration General Hospital of Eastern Theater Command of Chinese People’s Liberation ArmyNanjingJiangsu 210002P.R.China department of Medical oncology Zhejiang Cancer HospitalHangzhouZhejiang 310022P.R.China Cancer Center the First Bethune Hospital of Jilin UniversityChangchunJilin 130021P.R.China department of Medical oncology Harbin Medical University Cancer HospitalHarbinHeilongjiang 150081P.R.China department of Respiratory Medicine Weifang People’s HospitalWeifangShandong

Background:Lipusu is the first commercialized liposomal formulation of pacli-taxel and has demonstrated promising efficacy against locally advanced lung squamous cell carcinoma(LSCC)in a small-scale study.Here,we conducted a multicenter,randomized,phase 3 study to compare the efficacy and safety of cis-platin plus Lipusu(LP)versus cisplatin plus gemcitabine(GP)as first-line treat-ment in locally advanced or metastatic LSCC.Methods:Patients enrolled were aged between 18 to 75 years,had locally advanced(clinical stage IIIB,ineligible for concurrent chemoradiation or surgery)or metastatic(Stage IV)LSCC,had no previous systemic chemother-apy and at least one measurable lesion as per the Response Evaluation Criteria in Solid Tumors(version 1.1)before administration of the trial drug.The primary endpoint was progression-free survival(PFS).The secondary endpoints included objective response rate(ORR),disease control rate(DCR),overall survival(OS),and safety profiles.To explore the possible predictive value of plasma cytokines for LP treatment,plasma samples were collected from the LP group at baseline and first efficacy evaluation time and were then subjected to analysis by 45-Plex ProcartaPlex Panel 1 to detect the presence of 45 cytokines using the Luminex xMAP technology.The correlation between treatment outcomes and dynamic changes in the levels of cytokines were evaluated in preliminary analyses.Results:The median duration of follow-up was 15.4 months.237 patients in the LP group and 253 patients in the GP group were included in the per protocol set(PPS).In the PPS,the median PFS was 5.2 months versus 5.5 months in the LP and GP group(hazard rtio[HR]:1.03,P=0.742)respectively.The median OS was 14.6 months versus 12.5 months in the LP and GP group(HR:0.83,P=0.215).The ORR(41.8%versus 45.9%,P=0.412)and DCR(90.3%versus 88.1%,P=0.443)were also similar between the LP and GP group.A significantly lower proportion of patients in the LP group experienced adverse events(AEs)leading to treatment interruptions(10.9%versus 26.

关键词： chemotherapy cisplatin clinical trial gemcitabine liposomal paclitaxel(Lipusu) locally advanced lung squamous cell carcinoma metastatic multicenter plasma cytokines

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Identification of a three-gene prognostic signature for radioresistant esophageal squamous cell carcinoma

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World Journal of Clinical oncology 2023年第1期14卷 13-26页

作者： Xiao-Yan Wang Narasimha M Beeraka Nan-Nan Xue Hui-Ming Yu Ya Yang Mao-Xing Liu Vladimir N Nikolenko Jun-Qi Liu Di Zhao department of Endocrinology The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052Henan ProvinceChina department of radiation oncology The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052Henan ProvinceChina department of Human Anatomy I.M.Sechenov First Moscow State Medical UniversityMoscow 119991Russia department of pharmaceutical Chemistry JSS College of PharmacyMysuru 570015India department of radiation oncology Peking University Cancer Hospital&InstituteBeijing 065005China Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education) Department of Gastrointestinal Surgery ⅣPeking University Cancer Hospital&InstituteBeijingChina M.V.Lomonosov Moscow State University Moscow 119991Russia

BACKGROUND Esophageal squamous cell carcinoma(ESCC)is causing a high mortality rate due to the lack of efficient early prognosis markers and suitable therapeutic regimens.The prognostic role of genes responsible for the acquisition of radioresistance in ESCC has not been fully elucidated.AIM To establish a prognostic model by studying gene expression patterns pertinent to radioresistance in ESCC patients.METHODS Datasets were obtained from the Gene Expression Omnibus and The Cancer Genome Atlas databases.The edgeR,a Bioconductor package,was used to analyze mRNA expression between different groups.We screened genes specifically responsible for radioresistance to estimate overall survival.Pearson correlation analysis was performed to confirm whether the expression of those genes correlated with each other.Genes contributing to radioresistance and overall survival were assessed by the multivariate Cox regression model through the calculation ofβi and risk score using the following formula:∑^(n)_(i=1)βi×PSI.RESULTS We identified three prognostic mRNAs(cathepsin S[CTSS],cluster of differentiation 180[CD180],and SLP adapter and CSK-interacting membrane protein[SCIMP])indicative of radioresistance.The expression of the three identified mRNAs was related to each other(r>0.70 and P<0.05).As to 1-year and 3-year overall survival prediction,the area under the time-dependent receiver operating characteristic curve of the signature consisting of the three mRNAs was 0.716 and 0.841,respectively.When stratifying patients based on the risk score derived from the signature,the high-risk group exhibited a higher death risk and shorter survival time than the low-risk group(P<0.0001).Overall survival of the low-risk patients was significantly better than that of the highrisk patients(P=0.018).CONCLUSION We have developed a novel three-gene prognostic signature consisting of CTSS,CD180,and SCIMO for ESCC,which may facilitate the prediction of early prognosis of this malignancy.

关键词： Esophageal squamous cell carcinoma CTSS CD180 SCIMP Radioresistance TNM stage Prognosis

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Dynamic Landscapes of tRNA Transcriptomes and Translatomes in Diverse Mouse Tissues

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Genomics, Proteomics & Bioinformatics 2023年第4期21卷 834-849页

作者： Peng Yu Siting Zhou Yan Gao Yu Liang Wenbing Guo Dan Ohtan Wang Shuaiwen Ding Shuibin Lin Jinkai Wang Yixian Cun Center for Translational Medicine Precision Medicine InstituteThe First Affiliated HospitalSun Yat-sen UniversityGuangzhou 510080China department of radiation oncology Affiliated Cancer Hospital&Institute of Guangzhou Medical UniversityGuangzhou 510080China department of Medical Informatics Zhongshan School of MedicineSun Yat-sen UniversityGuangzhou 510080China Center for Stem Cell Biology and Tissue Engineering MOE Key Laboratory for Stem Cells and Tissue EngineeringSun Yat-sen UniversityGuangzhou 510080China RIKEN Center for Biosystems Dynamics Research Kobe 650-0047Japan Graduate School of Biostudies Kyoto UniversityKyoto 606-8501Japan Wuya College of Innovation Shenyang Pharmaceutical UniversityShenyang 110016China RNA Biomedical institute Sun Yat-sen Memorial HospitalSun Yat-sen UniversityGuangzhou 510080China

Although the function of tRNAs in the translational process is well established,it remains controversial whether tRNA abundance is tightly associated with translational efficiency(TE)in mammals.Moreover,how critically the expression of tRNAs contributes to the establishment of tissue-specific proteomes in mammals has not been well addressed.Here,we measured both tRNA expression using demethylase-tRNA sequencing(DM-tRNA-seq)and TE of mRNAs using ribosome-tagging sequencing(RiboTag-seq)in the brain,heart,and testis of mice.Remarkable variation in the expression of tRNA isodecoders was observed among different tissues.When the statistical effect of isodecoder-grouping on reducing variations is considered through permutating the anticodons,we observed an expected reduction in the variation of anticodon expression across all samples,an unexpected smaller variation of anticodon usage bias,and an unexpected larger variation of tRNA isotype expression at amino acid level.Regardless of whether or not they share the same anticodons,the isodecoders encoding the same amino acids are co-expressed across different tissues.Based on the expression of tRNAs and the TE of mRNAs,we find that the tRNA adaptation index(tAI)and TE are significantly correlated in the same tissues but not between tissues;and tRNA expression and the amino acid composition of translating peptides are positively correlated in the same tissues but not between tissues.We therefore hypothesize that the tissue-specific expression of tRNAs might be due to post-transcriptional mechanisms.This study provides a resource for tRNA and translation studies,as well as novel insights into the dynamics of tRNAs and their roles in translational regulation.

关键词： Translational efficiency Tissue-specific tRNA expression Codon usage bias Amino acid composition

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