1.Single-cell transcriptome reveals features of immune environment and mechanisms of immune escape in giant cell tumor of bone
Zhiwu REN ; Chao ZHANG ; Junyang LIU ; Yue XIE ; Zhichao LIAO ; Ting LI ; Xinyue LIU ; Ruwei XING ; Jianmin SONG ; Jilong YANG
Chinese Journal of Orthopaedics 2022;42(21):1441-1449
Objective:This study aims to reveal the special immune infiltrating environment and possible immune escape mechanism of giant cell tumor of bone through single-cell sequencing data.Methods:The fresh samples obtained from 4 patients with primary giant cell tumor of bone from January 2018 to December 2021 were collected, and single-cell transcriptome sequencing was performed on the 10X platform to explore the characteristics and immune environment of giant cell tumor of bone by using t-distributed stochastic neighbor embedding ( t-SNE). The main cell types and signal pathways of immune cell regulation and function in giant cell tumor of bone were observed by cell communication analysis. Results:Cell clustering, the definition of basic cell types, the classification of immune cells, and the mutual regulatory relationship between cell types were analyzed for 35 643 single-cell data from 4 giant cell tumor samples of bone. It was found that giant cell tumor of bone was composed of 9 basic cell types, in which the immune cells were mainly CD8 + T cells (51%) and the non-immune cells were mainly fibroblast like spindle stromal cells (74%). The immune infiltration of giant cell tumor of bone is dominated by cytotoxic CD8 + T cells and lacks exhausted CD8 + T cells. CD4 + T cells are characterized by high expression of immune checkpoint genes CTLA4 and TIGIT. In giant cell tumor of bone, immune cells mainly act on multinucleated osteoclast like giant cells through PARs and CCL signaling pathways, but not stromal cells. Conclusion:This study defined the main cell types of giant cell tumor of bone through single cell sequencing data, and further revealed the composition characteristics of its immune infiltration, and found that the target of its immune cells was mainly multinuclear osteoclast like giant cells, which provided effective information for further understanding the occurrence and development of giant cell tumor of bone.
2. Targeted therapy for malignant peripheral nerve sheath tumor: translational research and clinical application
Zhichao LIAO ; Chao ZHANG ; Xinyue LIU ; Zhiwu REN ; Jin XU ; Chunzhi ZHANG ; Yun YANG ; Ze ZHU ; Jilong YANG
Chinese Journal of Oncology 2019;41(9):648-653
Malignant peripheral nerve sheath tumor (MPNST) is a rare invasive soft tissue sarcoma that originates from peripheral nerve branches and peripheral nerve sheaths. Early radical surgery is an effective treatment for MPNST. Since it is insensitive to radiotherapy and chemotherapy, the disease manifests a rapid progression, poor prognosis and high mortality. In recent years, the translational researches on the driving factors and therapeutic targets of MPNST have been rapidly developed, including the pathways of NF1-Ras, Raf-MEK-ERK, PI3K-AKT-mTOR, Wnt signaling, and abnormal expressions of apoptotic proteins, the general loss of polycomb repressive complex 2 (PRC2), upregulation of the HDAC family, abnormal expressions of receptor tyrosine kinases, expressions of programmed cell death ligand (PD-L1), aurora kinase and various microRNAs.This review summarizes the current translational researches on potential therapeutic targets of MPNST, and the clinical trials which provide helpful information for MPNST targeted therapy.
3.Targeted therapy for malignant peripheral nerve sheath tumor: translational research and clinical application
Zhichao LIAO ; Chao ZHANG ; Xinyue LIU ; Zhiwu REN ; Jin XU ; Chunzhi ZHANG ; Yun YANG ; Ze ZHU ; Jilong YANG
Chinese Journal of Oncology 2019;41(9):648-653
Malignant peripheral nerve sheath tumor (MPNST) is a rare invasive soft tissue sarcoma that originates from peripheral nerve branches and peripheral nerve sheaths. Early radical surgery is an effective treatment for MPNST. Since it is insensitive to radiotherapy and chemotherapy, the disease manifests a rapid progression, poor prognosis and high mortality. In recent years, the translational researches on the driving factors and therapeutic targets of MPNST have been rapidly developed, including the pathways of NF1?Ras, Raf?MEK?ERK, PI3K?AKT?mTOR, Wnt signaling, and abnormal expressions of apoptotic proteins, the general loss of polycomb repressive complex 2 (PRC2), upregulation of the HDAC family, abnormal expressions of receptor tyrosine kinases, expressions of programmed cell death ligand (PD?L1), aurora kinase and various microRNAs.This review summarizes the current translational researches on potential therapeutic targets of MPNST, and the clinical trials which provide helpful information for MPNST targeted therapy.
4.Targeted therapy for malignant peripheral nerve sheath tumor: translational research and clinical application
Zhichao LIAO ; Chao ZHANG ; Xinyue LIU ; Zhiwu REN ; Jin XU ; Chunzhi ZHANG ; Yun YANG ; Ze ZHU ; Jilong YANG
Chinese Journal of Oncology 2019;41(9):648-653
Malignant peripheral nerve sheath tumor (MPNST) is a rare invasive soft tissue sarcoma that originates from peripheral nerve branches and peripheral nerve sheaths. Early radical surgery is an effective treatment for MPNST. Since it is insensitive to radiotherapy and chemotherapy, the disease manifests a rapid progression, poor prognosis and high mortality. In recent years, the translational researches on the driving factors and therapeutic targets of MPNST have been rapidly developed, including the pathways of NF1?Ras, Raf?MEK?ERK, PI3K?AKT?mTOR, Wnt signaling, and abnormal expressions of apoptotic proteins, the general loss of polycomb repressive complex 2 (PRC2), upregulation of the HDAC family, abnormal expressions of receptor tyrosine kinases, expressions of programmed cell death ligand (PD?L1), aurora kinase and various microRNAs.This review summarizes the current translational researches on potential therapeutic targets of MPNST, and the clinical trials which provide helpful information for MPNST targeted therapy.
5.Prevalence and correlates of depression among residents (more than 15 years old) in Hainan Province
Linlin YUE ; Xin YU ; Daqiang CHEN ; Dafei ZHAN ; Yanling HE ; Wentao CHEN ; Xianyun LI ; Qingxiong YANG ; Yongqiang LIN ; Kaining XU ; Weimin DANG ; Jindi HUANG ; Ling WU ; Zhiwu LIAO ; Rize JING ; Dan WANG ; Lei YANG ; Daqiu CHEN ; Zhiqing WANG ; Rui XU ; Fujun JIA ; Sheng HUANG ; Jialong YI ; Xianglai LIU ; Qiwen ZHANG ; Qiankun YAO ; Yongping HE ; Weifei YU ; Yunzhi ZHANG ; Hua YANG ; Haiya LIU ; Yemin CAI
Chinese Journal of Psychiatry 2019;52(3):212-218
Objective To investigate the prevalence and correlates of depression in residents aged 15 and older in Hainan province.Methods Stratified multistage random sampling methods were utilized to identify 12 117 individuals (≥15 years old) from 59 villages (neighborhoods) in 24 towns (streets) within 6 counties (cities) in Hainan Province from September 2010 to November 2011.The subjects were screened with an expanded version of the General Health Questionnaire (GHQ-12) and the respondents were divided into three groups by high risk,moderate risk and low risk of mental disorder,followed by formal diagnosis according to the Structured Clinical Interview for DSM-IV-TR (SCID-I/P) by psychiatrists among 100% subjects in group with high risk,40% subjects in group with moderate risk and 10% subjects in group with low risk.The adjusted rate,standardized rate,and 95% confidence interval (95%CI) of the one-month and lifetime prevalence were also calculated among the 3 groups of individuals who were diagnosed with depressive disorder.The difference in whether they suffered depression was determined by the chi-squared test.Correlations to depressive disorder and the odds ratio (OR) were explored with multiple regression analysis.Results There were 97 cases of depressive disorders (1-month) and 166 cases of lifetime depressive disorders finally confirmed.The adjusted rate of 1-month prevalence was 1.38% (95%CI:1.12-1.59) and the life-time adjusted prevalence rate was 2.80% (95%CI:2.51-3.09).Female (OR=1.55,95%CI:1.12-2.14),mid-age(50-64 y,OR=1.84,95%CI:1.13-2.99),being divorced or living separated (OR=4.87,95%CI:1.86-12.73),suffering chronic diseases (OR=2.19,95%CI:1.56-3.07),and low family income were significantly associated with suffering depressive disorder.Conclusions The prevalence of the depressive disorder among residents aged 15 and older in Hainan province is lower than the nationwide prevalence.People who are female,mid-age,being divorced or not living with the partner,earning a low income,and suffering chronic diseases have more predisposition to develop the depressive disorder in Hainan province.
6.Prevalence and correlates of depression among residents (more than 15 years old) in Hainan Province
Linlin YUE ; Xin YU ; Daqiang CHEN ; Dafei ZHAN ; Yanling HE ; Wentao CHEN ; Xianyun LI ; Qingxiong YANG ; Yongqiang LIN ; Kaining XU ; Weimin DANG ; Jindi HUANG ; Ling WU ; Zhiwu LIAO ; Rize JING ; Dan WANG ; Lei YANG ; Daqiu CHEN ; Zhiqing WANG ; Rui XU ; Fujun JIA ; Sheng HUANG ; Jialong YI ; Xianglai LIU ; Qiwen ZHANG ; Qiankun YAO ; Yongping HE ; Weifei YU ; Yunzhi ZHANG ; Hua YANG ; Haiya LIU ; Yemin CAI
Chinese Journal of Psychiatry 2019;52(3):212-218
Objective To investigate the prevalence and correlates of depression in residents aged 15 and older in Hainan province.Methods Stratified multistage random sampling methods were utilized to identify 12 117 individuals (≥15 years old) from 59 villages (neighborhoods) in 24 towns (streets) within 6 counties (cities) in Hainan Province from September 2010 to November 2011.The subjects were screened with an expanded version of the General Health Questionnaire (GHQ-12) and the respondents were divided into three groups by high risk,moderate risk and low risk of mental disorder,followed by formal diagnosis according to the Structured Clinical Interview for DSM-IV-TR (SCID-I/P) by psychiatrists among 100% subjects in group with high risk,40% subjects in group with moderate risk and 10% subjects in group with low risk.The adjusted rate,standardized rate,and 95% confidence interval (95%CI) of the one-month and lifetime prevalence were also calculated among the 3 groups of individuals who were diagnosed with depressive disorder.The difference in whether they suffered depression was determined by the chi-squared test.Correlations to depressive disorder and the odds ratio (OR) were explored with multiple regression analysis.Results There were 97 cases of depressive disorders (1-month) and 166 cases of lifetime depressive disorders finally confirmed.The adjusted rate of 1-month prevalence was 1.38% (95%CI:1.12-1.59) and the life-time adjusted prevalence rate was 2.80% (95%CI:2.51-3.09).Female (OR=1.55,95%CI:1.12-2.14),mid-age(50-64 y,OR=1.84,95%CI:1.13-2.99),being divorced or living separated (OR=4.87,95%CI:1.86-12.73),suffering chronic diseases (OR=2.19,95%CI:1.56-3.07),and low family income were significantly associated with suffering depressive disorder.Conclusions The prevalence of the depressive disorder among residents aged 15 and older in Hainan province is lower than the nationwide prevalence.People who are female,mid-age,being divorced or not living with the partner,earning a low income,and suffering chronic diseases have more predisposition to develop the depressive disorder in Hainan province.
7.TBX2 gene mutation and the clinical significance of related proteins expression in ma-lignant peripheral nerve sheath tumor
Fangyuan CHANG ; Xiaoling DU ; Hongji DAI ; Zhiwu REN ; Zhichao LIAO ; Jilong YANG
Chinese Journal of Clinical Oncology 2017;44(1):29-35
Objective:To detect genomic aberrations and investigate the expression and clinical significance of TBX2,CHK2, and p53 in malignant peripheral nerve sheath tumor (MPNST) tissues. Methods:We collected 63 cases of MPNST tissue samples, which were re-moved by resection and were confirmed by pathology, from January 1991 to December 2011 in Department of Bone and Sofer Tissue Tumor, Tianjin Medical University Cancer Institute and Hospital. Twelve fresh tumor samples with qualified DNA quality were selected from the above 63 cases of tissue samples. Genome abnormalities of 12 MPNST tissues were detected by next-generation sequencing. The protein expression levels of TBX2, CHK2, and p53 in 63 MPNST tissue samples were assessed by immunohistochemistry staining. Results:One case of TBX2 gene mutation was observed out of the 12 MPNST tissue samples. In 63 MPNST tissue samples, the protein expression rates of TBX2, CHK2, and p53 were 60.3%(38/63), 47.6%(30/63), and 30.2%(19/63), respectively. TBX2 expression was sig-nificantly correlated with AJCC (American Joint Committee on Cancer, AJCC) stage, recurrence, and metastasis (P<0.05). TBX2 expres-sion was directly correlated with that of CHK2 (r=0.254, P=0.045), and CHK2 expression was directly correlated with that of p53 (r=0.343, P=0.006). In terms of the disease-free survival and overall survival time, patients with high expression levels of TBX2, CHK2, and p53 had significantly worse prognosis than patients with low expression levels of TBX2, CHK2, and p53(all P<0.05). TBX2, CHK2, and p53 were independent prognostic factors of MPNST. Conclusion:TBX2 and its associated proteins may play important roles in MPNST development and progression. Detecting TBX2 expression may provide the theoretical basis for estimating the prognosis of patients with MPNST.

Result Analysis
Print
Save
E-mail