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Clinical and molecular significance of homologous recombination deficiency positive non-small cell lung cancer in Chinese population:An integrated genomic and transcriptional analysis

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Chinese Journal of Cancer Research 2024年第3期36卷 282-297页

作者： Yifei Wang Yidan Ma Lei He Jun Du Xiaoguang Li Peng Jiao Xiaonan Wu Xiaomao Xu Wei Zhou Li Yang Jing Di Changbin Zhu Liming Xu Tianlin Sun Lin Li Dongge Liu Zheng Wang Department of Pathology Department of minimally invasive Tumor Therapies center Department of thoracic surgery Department of Oncology Department of Respiratory and Critical Care Medicine Beijing HospitalNational Center of GerontologyInstitute of Geriatric MedicineChinese Academy of Medical SciencesBeijing 100730China Amoy Diagnostics Co. Ltd.Xiamen 361027China

Objective:The clinical significance of homologous recombination deficiency(HRD)in breast cancer,ovarian cancer,and prostate cancer has been established,but the value of HRD in non-small cell lung cancer(NSCLC)has not been fully *** study aimed to systematically analyze the HRD status of untreated NSCLC and its relationship with patient prognosis to further guide clinical ***:A total of 355 treatment-naïve NSCLC patients were retrospectively *** status was assessed using the AmoyDx Genomic Scar Score(GSS),with a score of≥50 considered ***,transcriptomic,tumor microenvironmental characteristics and prognosis between HRD-positive and HRDnegative patients were ***:Of the patients,25.1%(89/355)were *** to HRD-negative patients,HRDpositive patients had more somatic pathogenic homologous recombination repair(HRR)mutations,higher tumor mutation burden(TMB)(P<0.001),and fewer driver gene mutations(P<0.001).Furthermore,HRD-positive NSCLC had more amplifications in PI3K pathway and cell cycle genes,MET and MYC in epidermal growth factor receptor(EGFR)/anaplastic lymphoma kinase(ALK)mutant NSCLC,and more PIK3CA and AURKA in EGFR/ALK wild-type ***-positive NSCLC displayed higher tumor proliferation and immunosuppression ***-negative NSCLC showed activated signatures of major histocompatibility complex(MHC)-II,interferon(IFN)-γand effector memory CD8+T ***-positive patients had a worse prognosis and shorter progressionfree survival(PFS)to targeted therapy(first-and third-generation EGFR-TKIs)(P=0.042).Additionally,HRDpositive,EGFR/ALK wild-type patients showed a numerically lower response to platinum-free immunotherapy ***:Unique genomic and transcriptional characteristics were found in HRD-positive *** prognosis and poor response to EGFR-TKIs and immunotherapy were observed in HRD-positive *** study highlights potential actionable alterations in HRD

关键词： Non-small cell lung cancer homologous recombination deficiency genetic alterations transcriptional analysis tumor microenvironment prognosis

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The diagnostic value of tenascin-C in acute aortic syndrome

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Journal of Geriatric Cardiology 2024年第3期21卷 359-368页

作者： Ming MA Wei CHEN Hai-Long CAO Jun PAN Qing ZHOU Xin-Long TANG Dong-Jin WANG Department of thoracic and Cardiovascular surgery Nanjing Drum Tower Hospital Clinical College of Nanjing Medical UniversityNanjingChina Department of thoracic and Cardiovascular surgery Nanjing Drum Tower HospitalAffiliated Hospital of Medical SchoolNanjing UniversityNanjingChina Department of thoracic surgery Kunshan Hospital of Traditional Chinese MedicineJiangsuChina

OBJECTIVES Misdiagnosis of acute aortic syndrome(AAS)significantly increases ***-C(TN-C)is an extracellular matrix glycoprotein related to cardiovascular *** elevation of TN-C in AAS and whether it can discriminate suddenonset of acute chest pain in Chinese remains *** We measured the plasma concentration of TN-C by ELISA in a cohort of 376 patients with chest or back *** to discriminate AAS from acute coronary syndrome(ACS)were compared and *** From October 2016 to September 2021,376 undiagnosed patients with chest or back pain were enrolled.166 of them were finally diagnosed as AAS,100 were ACS and 110 without cardiovascular diseases(NCV).TN-C was significantly elevated in AAS at 18.18 ng/mL(IQR:13.10–27.68)compared with 7.51 ng/mL(IQR:5.67–11.38)in ACS(P<0.001)and 3.68 ng/mL(IQR:2.50–5.29)in NCV(P<0.001).There was no significant difference in TN-C level among the subtypes of *** the 166 AAS patients,the peaked level of TN-C was at acute stage(P=0.012),then a slight of decrease was observed at subacute *** area under receiver operating characteristic curve for AAS patients versus NCV was 0.979(95%CI:0.964-0.994)for *** a cutoff level of 11.474 ng/mL,TN-C has a sensitivity of 76.0%,specificity of 85.5%,accuracy of 82.0%,positive predictive value(PPV)of 76.0%,negative predictive value(NPV)of 85.5%.Diagnostic performance of TN-C was superior to D-dimer and *** The concentration of serum TN-C in AAS patients was significantly higher than that in ACS patients and ***-C could be a new biomarker to distinguish AAS patients in the early stage after symptoms onset from other pain diseases.

关键词： acute cardiovascular elevated

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TGF-βsignaling in health,disease,and therapeutics

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Signal Transduction and Targeted Therapy 2024年第4期9卷 1466-1505页

作者： Ziqin Deng Tao Fan Chu Xiao He Tian Yujia Zheng Chunxiang Li Jie He Department of thoracic surgery National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China

ransforming growth factor(TGF)-βis a multifunctional cytokine expressed by almost every tissue and cell *** signal transduction of TGF-βcan stimulate diverse cellular responses and is particularly critical to embryonic development,wound healing,tissue homeostasis,and immune homeostasis in *** dysfunction of TGF-βcan play key roles in many diseases,and numerous targeted therapies have been developed to rectify its pathogenic *** the past decades,a large number of studies on TGF-βsignaling have been carried out,covering a broad spectrum of topics in health,disease,and ***,a comprehensive overview of TGF-βsignaling is required for a general picture of the studies in this *** this review,we retrace the research history of TGF-βand introduce the molecular mechanisms regarding its biosynthesis,activation,and signal *** also provide deep insights into the functions of TGF-βsignaling in physiological conditions as well as in pathological ***-β-targeting therapies which have brought fresh hope to the treatment of relevant diseases are *** the summary of previous knowledge and recent updates,this review aims to provide a systematic understanding of TGF-βsignaling and to attract more attention and interest to this research area.

关键词： homeostasis healing wound

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Neoadjuvant camrelizumab(an anti-PD-1 antibody)plus chemotherapy or apatinib(a VEGFR-2 inhibitor)for initially unresectable stage II–III non-small-cell lung cancer:a multicentre,two-arm,phase 2 exploratory study

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Signal Transduction and Targeted Therapy 2024年第7期9卷 3015-3023页

作者： Haoran Xia Han Zhang Zheng Ruan Huibiao Zhang Liangdong Sun Hezhong Chen Yongxin Zhou Lele Zhang Dongliang Bian Xinsheng Zhu Jing Zhang Fenghuan Sun Huansha Yu Nan Song Xiaogang Liu Yuming Zhu Haiping Zhang Wenxin He Jian Chen Jie Yang Guohan Chen Shiliang Xie Dongfang Tang Xiaomiao Zhang Liang Duan Deping Zhao Qinchuan Li Peng Zhang Gening Jiang Department of thoracic surgery Shanghai Pulmonary HospitalTongji University School of MedicineShanghaiChina Department of thoracic surgery Shanghai General HospitalShanghai Jiao Tong University School of MedicineShanghaiChina Department of thoracic surgery Huadong Hospital Affiliated to Fudan UniversityShanghaiChina Department of thoracic surgery Changhai HospitalNaval Medical UniversityShanghaiChina Department of thoracic-Cardiovascular surgery Tongji HospitalTongji University School of MedicineShanghaiChina Central Laboratory Shanghai Pulmonary HospitalTongji University School of MedicineShanghaiChina Experimental Animal center Shanghai Pulmonary HospitalTongji University School of MedicineShanghaiChina Department of Oncology Shanghai Pulmonary HospitalTongji University School of MedicineShanghaiChina Department of thoracic surgery Shanghai East HospitalTongji University School of MedicineShanghaiChina

This multicentre,two-arm,phase 2 study aimed to explore the efficacy and safety of neoadjuvant camrelizumab plus chemotherapy or apatinib in patients with initially unresectable stage II–III non-small-cell lung cancer(NSCLC).Eligible patients regardless of PD-L1 expression received neoadjuvant camrelizumab 200 mg and platinum-doublet chemotherapy every 3 weeks(arm A)or those with PD-L1-positive tumors received neoadjuvant camrelizumab and apatinib 250 mg once daily(arm B),for 2–4 cycles,followed by *** primary endpoint was major pathological response(MPR)*** patients in arm A and 21 in arm B were *** rates were 50.0%(15/30)in arm A and 42.9%(9/21)in arm B,with all patients achieving R0 *** these patients,the MPR and pathological complete response rates were both 20.0%(95%CI 4.3–48.1)in arm A and were 55.6%(95%CI 21.2–86.3)and 11.1%(95%CI 0.3–48.2)in arm B,*** corresponding objective response rates were 33.3%(95%CI 11.8–61.6)and 55.6%(95%CI 21.2–86.3).With a median follow-up of 22.4 months(95%CI 19.0–26.0),the median event-free survival was not reached(NR;95%CI 13.6-NR)in arm A and 16.8 months(95%CI 8.6-NR)in arm *** 3 or above treatment-related adverse events occurred in eight(26.7%)patients in arm A and three(14.3%)in arm *** analysis showed baseline TYROBP expression was predictive of treatment response in arm *** camrelizumab plus chemotherapy or apatinib exhibits preliminary efficacy and manageable toxicity in patients with initially unresectable stage II–III NSCLC.

关键词： surgery chemotherapy treatment

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Systematic analysis of DNA polymerases as therapeutic targets in pan-cancers

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BIOCELL 2024年第1期48卷 123-138页

作者： ZHENHUA LI HUILAI LV FAN ZHANG ZIMING ZHU QIANG GUO MINGBO WANG CHAO HUANG LIJUAN CHEN WENPAN ZHANG YUN LI ZIQIANG TIAN Department of thoracic surgery Fourth Hospital of Hebei Medical UniversityShijiazhuang050011China Department of thoracic surgery The First Hospital of XingtaiXingtai054001China Department of thoracic surgery Affiliated Hospital of Hebei UniversityBaoding050017China Shanghai OrigiMed Co. Ltd.Shanghai200000China Department of thoracic surgery The Seventh Affiliated Hospital of Sun Yat-sen UniversityShenzhen518107China

Introduction:DNA polymerases are crucial for maintaining genome stability and influencing ***,the clinical implications of DNA polymerases in tumorigenesis and their potential as anti-cancer therapy targets are not well ***:We conducted a systematic analysis using TCGA Pan-Cancer Atlas data and Gene Set Cancer Analysis results to examine the expression profiles of 15 DNA polymerases(POLYs)and their clinical *** also evaluated the prognostic value of POLYs by analyzing their expression levels in relation to overall survival time(OS)using Kaplan-Meier survival ***,we investigated the correlations between POLY expression and immune cells,DNA damage repair(DDR)pathways,and *** sensitivity analysis was performed to assess the relationship between POLY expression and drug ***:Our analysis revealed that 14 out of 15 POLYs exhibited significantly distinct expression patterns between tumor and normal samples across most cancer types,except for DNA nucleotidylexotransferase(DNTT).Specifically,POLD1 and POLE showed elevated expression in almost all cancers,while POLQ exhibited high expression levels in all cancer *** POLYs showed heightened expression in specific cancer subtypes,while others exhibited low ***-Meier survival curves demonstrated significant prognostic value of POLYs in multiple cancers,including PAAD,KIRC,and *** analysis further validated these *** patterns of POLYs varied significantly among different cancer types and were associated with poorer survival *** correlations were observed between the expression of POLY members and immune cells,DDR pathways,and *** sensitivity analysis indicated an inverse relationship between POLY expression and drug ***:Our comprehensive study highlights the significant role of POLYs in cancer development and identifies them as promising prognostic and

关键词： DNA polymerases(POLYs) Prognostic biomarker The Cancer Genome Atlas(TCGA) Ubiquitination network

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Promising prognostic value of ATP binding cassette transporters and their correlation with tumor-infiltrating immune cells in lung adenocarcinoma

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Genes & Diseases 2024年第5期11卷 91-93页

作者： Linzi Wei Qian Yu Xueying Yang Department of thoracic surgery The Fourth Affiliated Hospital of China Medical UniversityShenyangLiaoning 110032China

Lung cancer(LC)is a prevalent and fatal malignancy,with high incidence and mortality rates.1 ATP binding cassette(ABC)transporters,a superfamily of integral membrane proteins,use ATP hydrolysis to facilitate substrate transport across cellular membranes.2 The pivotal role of ABC transporters in tumorigenesis was initially established by Mochida,3 who demonstrated that the loss of ABCB1 suppresses intestinal polyp formation and tumor progression in *** investigations have reported correlations between ABC transporters and the tumor microenvironment and cancer immunotherapy response,suggesting their modulatory effects on tumor progression and immunotherapy.

关键词： mortality adenocarcinoma Lung

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Stem cell technology for antitumor drug loading and delivery in oncology

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Oncology Research 2024年第3期32卷 433-437页

作者： FRANCESCO PETRELLA ENRICO MARIO CASSINA LIDIA LIBRETTI EMANUELE PIRONDINI FEDERICO RAVEGLIA ANTONIO TUORO Department of thoracic surgery Fondazione IRCCSS an Gerardo dei TintoriMonza20900Italy

The main aim of antineoplastic treatment is to maximize patient benefit by augmenting the drug accumulation within affected organs and tissues,thus incrementing drug effects and,at the same time,reducing the damage of non-involved tissues to cytotoxic *** stromal cells(MSC)represent a group of undifferentiated multipotent cells presenting wide self-renewal features and the capacity to differentiate into an assortment of mesenchymal family *** the last year,they have been proposed as natural carriers for the selective release of antitumor drugs to malignant cll,s thus optimizing cytotoxic action on cancer cll,while significantly reducing adverse side efect on healthy *** chemotherapeutic drug loading and delivery is an encouraging new area of cell therapy for several tumors,especially for those with unsatisfactory prognosis and limited treatment options *** some experim ental models have been sucesfuly developed,phase I dinical studies are needed to confirm this potential application of cell therapy,in particular in the case of primary and secondary lung cancers.

关键词： Mesenchymal stromal cell Drug loading Drug delivery Mesothelioma Melanoma Glioblastoma Pancreatic ductal adenocarcinoma Multiple myeloma

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Diagnostic Value of GDF10 for the Tumorigenesis and Immune Infiltration in Lung Squamous Cell Carcinoma

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Current Medical Science 2024年第2期44卷 309-327页

作者： Xiao-jun WANG Jia-ping CHEN Xin-wei QIAO Wang-yang MENG Yang-wei WANG Yun-chong MENG Rong ZHAO Wei LIN Yong-de LIAO Han XIAO Pei-yuan MEI Department of thoracic surgery Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430022China Department of thoracic surgery Shandong Provincial Hospital Affiliated to Shandong First Medical UniversityJinan 250021China

Objective:Lung squamous cell carcinoma(LUSC)is associated with a low survival *** suggests that bone morphogenetic proteins(BMPs)and their receptors(BMPRs)play crucial roles in tumorigenesis and ***,a comprehensive analysis of their role in LUSC is *** study aimed to explore the relationship between BMPs/BMPRs expression levels and the tumorigenesis and prognosis of ***:The“R/Limma”package was utilized to analyze the differential expression characteristics of BMPs/BMPRs in LUSC,using data from TCGA,GTEx,and GEO ***,the“survminer”packages were employed to investigate their prognostic value and correlation with clinical features in *** core gene associated with LUSC progression was further explored through weighted gene correlation network analysis(WGCNA).LASSO analysis was conducted to construct a prognostic risk model for *** specimens were examined by immunohistochemical analysis to confirm the diagnostic value in ***,based on the tumor immune estimation resource database and tumor-immune system interaction database,the role of the core gene in the tumor microenvironment of LUSC was ***:GDF10 had a significant correlation only with the pathological T stage of LUSC,and the protein expression level of GDF10 decreased with the tumorigenesis of LUSC.A prognostic risk model was constructed with GDF10 as the core gene and 5 hub genes(HRASLS,HIST1H2BH,FLRT3,CHEK2,and ALPL)for ***10 showed a significant positive correlation with immune cell infiltration and immune checkpoint ***:GDF10 might serve as a diagnostic biomarker reflecting the tumorigenesis of LUSC and regulating the tumor immune microenvironment to guide more effective treatment for LUSC.

关键词： lung squamous cell carcinoma tumorigenesis bone morphogenetic protein GDF10 tumor immune microenvironment

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Identification of tumor-suppressor genes in lung squamous cell carcinoma through integrated bioinformatics analyses

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Oncology Research 2024年第1期32卷 187-197页

作者： HENG LI YOUMING LEI GAOFENG LI YUNCHAO HUANG The 2nd Department of thoracic surgery The Third Affiliated Hospital of Kunming Medical UniversityYunnan Tumor HospitalKunming650118China The 1st Department of thoracic surgery The Third Affiliated Hospital of Kunming Medical UniversityYunnan Tumor HospitalKunming650118China Department of Geriatric thoracic surgery The First Affiliated Hospital of Kunming Medical UniversityKunming650032China

Lung cancer is a prevalent malignancy,and fatalities of the disease exceed 400,000 cases *** squamous cell carcinoma(LUSC)has been recognized as the most common pathological form of lung *** comprehensive understanding of molecular features related to LUSC progression has great significance in LUSC prognosis assessment and clinical *** this study,we aim to identify a panel of signature genes closely associated with LUSC,which can provide novel insights into the progression of *** expression profiles were retrieved from public resources including gene expression omnibus(GEO)and the cancer genome atlas(TCGA)*** expressed genes(DEGs)between LUSC specimens and normal lung tissues were identified by bioinformatics analyses.A total of 66 DEGs were identified based on two cohorts of *** plugin of Cytoscape software was utilized for the further analyses of the top 10 candidate hub genes including OGN,ABI3BP,MAMDC2,FGF7,FAM107A,SPARCL1,DCN,COL14A1,and MFAP4 and CHRDL1,which showed significant downregulation in *** LUSC cell lines were used to validate the functions of CHRDL1 and FAM107A through overexpression ***,our data revealed novel candidate tumor-suppressor genes in LUSC,suggesting previously unappreciated mechanisms in the progression of LUSC.

关键词： LUSC DEGs WGCNA PPI network Tumor-suppressor

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Tet methylcytosine dioxygenase 2(TET2)deficiency elicits EGFR-TKI(tyrosine kinase inhibitors)resistance in non-small cell lung cancer

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Signal Transduction and Targeted Therapy 2024年第4期9卷 1706-1720页

作者： Jian Zhang Kejia Zhao Wenjing Zhou Ran Kang Shiyou Wei Yueli Shu Cheng Yu Yin Ku Yonghong Mao Hao Luo Juqin Yang Jiandong Mei Qiang Pu Senyi Deng Zhengyu Zha Gang Yuan Shensi Shen Yaohui Chen Lunxu Liu Department of thoracic surgery and Institute of thoracic Oncology West China Hospital of Sichuan UniversityChengdu 610097China Western China Collaborative Innovation center for Early Diagnosis and Multidisciplinary Therapy of Lung Cancer Sichuan UniversityChengdu 610097China Biobank of West China Hospital Sichuan UniversityChengdu 610041China

Despite epidermal growth factor receptor(EGFR)tyrosine kinase inhibitors(TKl)have shown remarkable efficacy in patients with EGFR-mutant non-small cell lung cancer(NSCLC),acquired resistance inevitably develops,limiting clinical *** found that TET2 was poly-ubiquitinated by E3 ligase CUL7^(FBXW11) and degraded in EGFR-TKI resistant NSCLC *** perturbationof TET2 rendered parental cells more tolerant to TKI ***2 was stabilized by MEK1 phosphorylation at Ser 1107,while MEK1 inactivation promoted its proteasome degradation by enhancing the recruitment of CUL7^(FBXW11),Loss of TET2 resulted in the upregulation of TNF/NF-kB signaling that confers the EGFR-TKI *** or pharmacological inhibition of NF-kB attenuate the TKI resistance both in vitro and in *** findings exemplified how a cell growth controlling kinase MEK1 leveraged the epigenetic homeostasis by regulating TET2,and demonstrated an alternative path of non-mutational acquired EGFR-TKI resistance modulated by TET2 ***,combined strategy exploiting EGFR-TKI and inhibitors of TET2/NF-κB axis holds therapeutic potential for treating NSCLC patients who suffered from this resistance.

关键词： TET2 TKI resistance

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