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第十四届全国免疫学学术大会

作者： Yingting Liu Jingting Jiang Department of Tumor Biological Treatment the Third Affiliated Hospital of Soochow University

Background:Interleukin-1 receptor type 2(IL1 R2) is characterized as a member of the IL-1 family.It acts as a decoy receptor of IL-1,blocking the IL-1-induced pro-inflammatory signals and performing a negative regulation in the inflammation process.Recently,numerous studies showed that IL1 R2 expressed differentially in various tumors,suggesting that IL1 R2 might be involved in tumorigenesis and progression.Up to now,the potential role of IL1 R2 in human kidney carcinoma has not been reported.Here in this study,we aimed to examine the expression pattern as well as the clinical significance of IL1 R2 in human kidney renal clear cell carcinoma(KIRC) and explore its contribution in the regulation of the malignant phenotype in kidney renal clear cell carcinoma cells.Methods:The immunohistochemistry assay was used to examine the IL1 R2 expression in human KIRC tissues and analyzed the correlation between IL1 R2 expression and patients’ clinical parameters.IL1 R2 knockdown and overexpression stable kidney renal clear cell carcinoma cell lines were established by transducing lentivirus into 786-O and ACHN.The cellular studies were performed to investigate the roles of IL1 R2 in the regulation of biological functions in kidney renal clear cell carcinoma cell lines.We also identified the diffe rentially expressed genes upon IL1 R2 depletion in KIRC cell lines by using RNA-seq analysis.Results:The data analyses from the TCGA database and immunohistochemistry results demonstrated that the expression of IL1 R2 in KIRC tissues significantly correlated with pathological stage and patients’ prognoses.IL1 R2 expression could serve as an independent prognostic predictor for KIRC patients.The cellular functional studies of knockdown IL1 R2 expression KIRC cell lines revealed that decreased IL1 R2 expression could inhibit cell proliferation,migration,invasion and cell cycle arrest at G1 phase while IL1 R2 overexpression could appear the opposite results.In addition,according to the RNA-sequencing analysis data,the phosphorylated ex

关键词： Interleukin-1 receptor type 2 kidney renal clear cell carcinoma Prognosis Biological function

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The combination of NDUFS1 with immune infiltration predicts favorable prognosis in kidney renal clear cell carcinoma

The combination of NDUFS1 with immune infiltration predicts ...

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2021年中国肿瘤标志物学术大会暨第十五届肿瘤标志物青...

作者： Dong Wu Zhe Xu Ling Li The Fourth Military Medical University

Purpose: kidney renal clear cell carcinoma(KIRC), the most common malignant tumor of the urinary system, is an immunogenic tumor, and KIRC patients therapeutic response and prognosis are relevant to immune infiltration. NDUFS1, the core subunit of mitochondria complex I(CI) in the respiratory chain, participating in the procedure of electron transport has been reported to be associated with the occurrence and development of tumors and be down-regulated in KIRC and associated with poor prognosis. However, the upstream regulator for NDUFS1 and their correlations with immune infiltration or patients survival remain unclear. Here, we tried to elucidate the immunological mechanism and clinical significance of NDUFS genes in KIRC.Methods: The expression of NDUFS genes in KIRC and their influences on patients survival were investigated by UALCAN, ENCORI(The Encyclopedia of RNA Interactomes), GEPIA(Gene Expression Profiling Interactive Analysis), Oncomine, TIMER(Tumor Immune Estimation Resource site) and Kaplan-Meier Plotter. MiR NAs regulating NDUFS1 in KIRC were predicted and analyzed by TargetScan and ENCORI. The correlations between NDUFS1 or miRNAs expression with immune cell infiltration or gene marker sets of immune infiltrates were analyzed via TIMER. The overall survival curves in high/low NDUFS1 or high/low hsa-miR-320 b expressed KIRC patients based on immune infiltration were analyzed via Kaplan-Meier Plotter.Results: From comprehensive bioinformatic analysis through digging into public online databases, we consistently found that in NDUFS gene family, NDUFS1 was significantly down-regulated in KIRC,high expression of NDUFS1, NDUFS4 predict good overall survival(OS) prognosis, and high expression of NDUFS1, NDUFS2, and NDUFS4 are correlated with good disease-free survival(DFS)prognosis. Moreover, the expression of NDUFS1 negatively correlates with advanced tumor grades and individual cancer stages, demonstrating that NDUFS1 may serve as a tumor suppressor gene in KIRC. NDUFS1 expression was positively correla

关键词： kidney renal clear cell carcinoma NDUFS1 survival expression immune infiltration hsa-miR-320b

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Low expression of fatty acid oxidation related gene ACADM indicates poor prognosis of renal clear cell carcinoma and is related to tumor immune infltration

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Oncology Research 2024年第3期32卷 545-561页

作者： JIECHUAN QIU TIANMIN YANG YANNING SUN KAI SUN YINGKUN XU QINGHUA XIA Department of Urology Shandong Provincial Hospital A fliated to Shandong First Medical UniversityJinan250021China Depatment of Urology Shandong Provincial HospitalCheeloo College of MedicineShandong UniversityJinan250021China Depatment of Breast and Thyroid Surgery The First Afiliated Hospital of Chongqing Medical UniversityChongqing400042China

This research aims to identify the key fatty acid beta-oxidation(FAO)genes that are altered in kidney renal clear cell carcinoma(KIRC)and to analyze the role of these genes in KIRC The Gene Expression Omnibus(GEO)and FAO datasets were used to identify these key genes.Wilcoxon rank sum test was used to assess the levels of acyl-CoA dehydrogenase medium chain(ACADM)between KIRC and non cancer samples.The logistic regression and Wilcoxon rank sum test were used to explore the association between ACADM and clinical features.The diagnostic performance of ACADM for KIRC was asessed using a diagnostic receiver operating ch aracteristic(ROC)curve.The co-expressed genes of ACADM were identifed in LinkedOmics database,and their function and pathway enrichment were analyzed.The correlation between ACADM expression level and immune infitration was analyzed by Gene Set Variation Analysis(GSVA)method Additionally,the proliferation,migration,and invasion abilities of KIRC cells were assessed after overexpressing ACADM.Following differential analysis and intersection,we identifed six hub genes,induding ACADM.We found that the expression level of ACADM was decreased in KIRC tissues and had a better diagnostic efect(AUC=0.916).Survival analysis suggested that patients with decreased ACADM expression had a worse prognosis.According to correlation analysis,a variety of dinical features were associated with the expression level of ACADML By analyzing the infiltration level of immune cells,we found that ACADM may be related to the enrichment of immune cells.Finally,ACADM overexpression inhibited proliferation,migration,and invasion of KIRC cells.In conclusion,our findings suggest that reduced ACADM expression in KIRC patients is indicative of poor prognosis.These results imply that ACADM may be a diagnostic and prognostic marker for individuals with KIRC,offering a reference for dinicians in diagnosis and treatment.

关键词： kidney renal clear cell carcinoma Acyl CoA dehydrogenase medium chain Immune infiltration Fatty acid oxidation Prognosis

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Innate immune checkpoint Siglec10 in cancers:mining of comprehensive omics data and validation in patient samples

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Frontiers of Medicine 2022年第4期16卷 596-609页

作者： Chen Zhang Jiandong Zhang Fan Liang Han Guo Sanhui Gao Fuying Yang Hua Guo Guizhen Wang Wei Wang Guangbiao Zhou State Key Laboratory of Membrane Biology Institute of ZoologyChinese Academy of Sciences&University of Chinese Academy of SciencesBeijing 100101China State Key Laboratory of Molecular Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China Department of Urology Beijing Chaoyang HospitalCapital Medical UniversityBeijing 100020China Shanxi Bethune Hospital Affiliated with Shanxi Academy of Medical Sciences Taiyuan 030032China

Sialic acid binding Ig-like lectin 10(Siglec10)is a member of innate immune checkpoints that inhibits the activation of immune cells through the interaction with its ligand CD24 on tumor cells.Here,by analyzing public databases containing 64517 patients of 33 cancer types,we found that the expression of Siglec10 was altered in 18 types of cancers and was associated with the clinical outcomes of 11 cancer types.In particular,Siglec10 was upregulated in patients with kidney renal clear cell carcinoma(KIRC)and was inversely associated with the prognosis of the patients.In 131 KIRC patients of our settings,Siglec10 was elevated in the tumor tissues of 83(63.4%)patients compared with that in their counterpart normal kidney tissues.Moreover,higher level of Siglec10 was associated with advanced disease(stages III and IV)and worse prognosis.Silencing of CD24 in KIRC cells significantly increased the number of Siglec10-expressing macrophages phagocytosing KIRC cells.In addition,luciferase activity assays suggested that Siglec10 was a potential target of the transcription factors c-FOS and GATA1,which were identified by data mining.These results demonstrate that Siglec10 may have important oncogenic functions in KIRC,and represents a novel target for the development of immunotherapies.

关键词： innate immune checkpoint Siglec10 kidney renal clear cell carcinoma

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Inhibition of Cyclin F Promotes cellular Senescence through Cyclin-dependent Kinase 1-mediated cell Cycle Regulation

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Current Medical Science 2023年第2期43卷 246-254页

作者： Xun LI You-jian LI Meng-jie WANG Ke-peng OU Ya-qi CHEN GI Cancer Research Institute Tongji HospitalHuazhong University of Science and TechnologyWuhan430030China College of Pharmacy National&Local Joint Engineering Research Center of Targeted and Innovative TherapeuticsChongqing Key Laboratory of Kinase Modulators as Innovative MedicineChongqing University of Arts and SciencesChongqing402160China Department of Obstetrics and Gynecology Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430030China College of Pharmaceutical Sciences and Chinese Medicine Southwest UniversityChongqing400715China

Objective kidney renal clear cell carcinoma(KIRC)is a common renal malignancy that has a poor prognosis.As a member of the F box family,cyclin F(CCNF)plays an important regulatory role in normal tissues and tumors.However,the underlying mechanism by which CCNF promotes KIRC proliferation still remains unclear.Methods Bioinformatics methods were used to analyze The Cancer Genome Atlas(TCGA)database to obtain gene expression and clinical prognosis data.The CCK8 assay,EdU assay,and xenograft assay were used to detect cell proliferation.The cell senescence and potential mechanism were assessed by SA-β-gal staining,Western blotting,as well as ELISA.Results Our data showed that CCNF was highly expressed in KIRC patients.Meanwhile,downregulation of CCNF inhibited cell proliferation in vivo and in vitro.Further studies showed that the reduction of CCNF promoted cell senescence by decreasing cyclin-dependent kinase 1(CDK1),increasing the proinflammatory factors interleukin(IL)-6 and IL-8,and then enhancing the expression of p21 and p53.Conclusion We propose that the high expression of CCNF in KIRC may play a key role in tumorigenesis by regulating cell senescence.Therefore,CCNF shows promise as a new biomarker to predict the clinical prognosis of KIRC patients and as an effective therapeutic target.

关键词： cyclin F kidney renal clear cell carcinoma clinical outcome cyclin-dependent kinase 1 senescence

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