BACKGROUND Hepatocellular carcinoma(HCC)is a common cancer with a poor prognosis.Previous studies revealed that the tumor microenvironment(TME)plays an important role in HCC progression,recurrence,and metastasis,leadi...BACKGROUND Hepatocellular carcinoma(HCC)is a common cancer with a poor prognosis.Previous studies revealed that the tumor microenvironment(TME)plays an important role in HCC progression,recurrence,and metastasis,leading to poor prognosis.However,the effects of genes involved in TME on the prognosis of HCC patients remain unclear.Here,we investigated the HCC microenvironment to identify prognostic genes for HCC.AIM To identify a robust gene signature associated with the HCC microenvironment to improve prognosis prediction of HCC.METHODS We computed the immune/stromal scores of HCC patients obtained from The Cancer Genome Atlas based on the ESTIMATE algorithm.Additionally,a risk score model was established based on Differentially Expressed Genes(DEGs)between high and lowimmune/stromal score patients.RESULTS The risk score model consisting of eight genes was constructed and validated in the HCC patients.The patients were divided into high-or low-risk groups.The genes(Disabled homolog 2,Musculin,C-X-C motif chemokine ligand 8,Galectin 3,B-cell-activating transcription factor,Killer cell lectin like receptor B1,Endoglin and adenomatosis polyposis coli tumor suppressor)involved in our risk score model were considered to be potential immunotherapy targets,and they may provide better performance in combination.Functional enrichment analysis showed that the immune response and T cell receptor signaling pathway represented the major function and pathway,respectively,related to the immune-related genes in the DEGs between high-and low-risk groups.The receiver operating characteristic(ROC)curve analysis confirmed the good potency of the risk score prognostic model.Moreover,we validated the risk score model using the International Cancer Genome Consortium and the Gene Expression Omnibus database.A nomogram was established to predict the overall survival of HCC patients.CONCLUSION The risk score model and the nomogram will benefit HCC patients through personalized immunotherapy.展开更多
Using the chronic obstructive pulmonary disease (COPD) medical records from January 1st to December 31st of 2013 and the Meteorological observation data, the air pollution data in the same time periods, generalized ad...Using the chronic obstructive pulmonary disease (COPD) medical records from January 1st to December 31st of 2013 and the Meteorological observation data, the air pollution data in the same time periods, generalized additive models were used to quantitatively analyze the relationship between COPD hospitalizations and temperature with controlling the confounding effects of time trend, meteorological factors and air pollution index (AQI). Results showed: variable temperature in 24 h (BT), 3d lagged minimum temperature (Tm3) and 5d lagged diurnal maximum temperature and minimum temperature range (Tc5) have different effects on COPD hospitalizations. When BT is between -4.4°C and -0.7°C, the relative risk (RR) increases to 1.0207 (95% CI: 1.0074 - 1.0342)with every 1°C increase in BT;when Tm3 is between -3.6°C and 3.2°C, the relative risk (RR) increases to 1.0118 (95% CI: 1.0015 - 1.0222)with every 1°C increase in Tm3, and when Tm3 is greater than 20.5°C, the relative risk (RR) increases to 1.0069 (95% CI: 1.0005 - 1.0133) with every 1°C increase in Tm3;when Tc5 is between 0.9°C and 8.6°C, if the Tc5 increases 1°C, the relative risk (RR) increases to 1.0125 (95% CI: 1.0066 - 1.0185. There are different effects for weather in different seasons on COPD hospitalizations: in autumn and winter, it is mainly of little BT and heavy air pollution weather;in spring, the large Tc5 weather is a main feature, and in summer, it’s mainly of high temperature and low pressure weather. The results help to provide some guidance on COPD forecasting services.展开更多
BACKGROUND Hepatitis B virus (HBV) has been recognized as a leading cause of hepatocellular carcinoma (HCC). Numerous reports suggest that immune infiltration can predict the prognosis of HCC. Nonetheless, no creditab...BACKGROUND Hepatitis B virus (HBV) has been recognized as a leading cause of hepatocellular carcinoma (HCC). Numerous reports suggest that immune infiltration can predict the prognosis of HCC. Nonetheless, no creditable markers for prognosis of HBV-related HCC have been established by systematically assessing the immune-related markers based on tumor transcriptomes. AIM To establish an immune-related marker based on the cell compositions of immune infiltrate obtained based on tumor transcriptomes, so as to enhance the prediction accuracy of HBV-related HCC prognosis. METHODS RNA expression patterns as well as the relevant clinical data of HCC patients were obtained from The Cancer Genome Atlas. Twenty-two immunocyte fraction types were estimated by cell type identification by estimating relative subsets of RNA transcripts. Subsequently, the least absolute shrinkage and selection operator (LASSO) Cox regression model was employed to construct an immunoscore based on the immunocyte fraction types. Afterwards, the receiver operating characteristic (ROC) curve, Kaplan-Meier, and multivariate Cox analyses were performed. Additionally, a nomogram for prognosis that integrated the immunoscore as well as the clinical features was established. Meanwhile, the correlation of immunoscore with immune genes was also detected, and gene set enrichment analysis (GSEA) of the immunoscore was conducted. RESULTS A total of 22 immunocyte fraction types were predicted and compared among the tumor as well as non-tumor samples. An immunoscore was constructed through adopting the LASSO model, which contained eight immunocyte fraction types. Meanwhile, the areas under the ROC curves for the immunoscore biomarker prognostic model were 0.971, 0.912, and 0.975 for 1-, 3-, and 5-year overall survival (OS), respectively. Difference in OS between the high-immunoscore group and the low-immunoscore group was statistically significant [hazard ratio (HR)= 66.007, 95% confidence interval (CI): 8.361-521.105;P < 0.0001]. Moreover, multivariable analysis showed that the immunoscore was an independent factor for predicting the prognosis (HR = 2.997, 95%CI: 1.737-5.170). A nomogram was established, and the C-index was 0.757 (95%CI: 0.648-0.866). The immunoscore showed a significant negative correlation with the expression of PD-1 (P = 0.024), PD-L1 (P = 0.026), PD-L2 (P = 0.029), and CD27 (P = 0.033). Eight pathways were confirmed by GSEA. CONCLUSION The established immunoscore can potentially serve as a candidate marker to estimate the OS for HBV-related HCC cases.展开更多
目的构建并验证一种头颈鳞状细胞癌(head and neck squamous cell carcinoma,HNSCC)自噬相关基因预后风险评分模型。方法从癌症基因组图谱(The Cancer Genome Atlas,TCGA)数据库下载全部HNSCC转录组表达数据(RNA sequencing,RNA-seq)及...目的构建并验证一种头颈鳞状细胞癌(head and neck squamous cell carcinoma,HNSCC)自噬相关基因预后风险评分模型。方法从癌症基因组图谱(The Cancer Genome Atlas,TCGA)数据库下载全部HNSCC转录组表达数据(RNA sequencing,RNA-seq)及临床信息,筛选出差异表达基因,与GeneCards数据库检索的自噬相关基因(autophagy related genes,ARGs)取交集,得到差异表达的ARGs,整合临床信息后经预后分析获得预后相关的ARGs,再对其富集分析。应用套索(the least absolute shrinkage and selection operator,LASSO)回归和Cox回归模型构建一种用于预测HNSCC预后及生存情况的风险评分模型;绘制受试者工作特征(receiver operating characteristic,ROC)曲线,计算曲线下面积(area under the curve,AUC)及最佳截断(cut-off)值,并以最佳cut-off值将患者分为高、低风险评分组;绘制Kaplan-Meier生存曲线评价该模型的预测性能;将临床信息与风险评分对应整合,再次利用Cox回归分析评价风险评分的独立预后价值。结果通过对差异表达的ARGs进行预后分析初筛出20个与预后相关的ARGs,再应用LASSO回归和Cox回归分析获得9个与预后显著相关的ARGs,以此构建HNSCC的预后风险评分模型。ROC曲线及Kaplan-Meier生存曲线分析显示,低风险评分组生存时间优于高风险评分组,两组生存时间差异有统计学意义(P<0.001),且该模型在训练集(AUC最大值为0.69)与外部验证集(AUC最大值为0.822)中均展现出良好的预测性能。纳入临床信息后,对风险评分进行Cox回归分析,提示其与HNSCC患者预后显著相关(P<0.001),表明风险评分对HNSCC具有独立预后价值。结论由9个ARGs组成的HNSCC风险评分模型,可有效预测HNSCC患者的预后情况。展开更多
Objectives The purposes were to determine the relationship between silicosis among foundry workers and their cumulative exposure to silica dust, and to establish a regression model to predict the risk for developing s...Objectives The purposes were to determine the relationship between silicosis among foundry workers and their cumulative exposure to silica dust, and to establish a regression model to predict the risk for developing silicosis by a given length of employment and air concentrations of silica at worksites. Methods A 29-year cohort study was conducted, including all those employed for more than one year during January 1, 1980 to December 31, 1996 and all members of the cohort were followed-up to December 3 1, 2008. In total, 2 009 workers of an automobile foundry in Shiyan, Hubei province were recruited in the study, 1 300 at eight worksites including sand preparation, cast shakeout, and finishing, melting, moulding, core-making, overhead crane operation and pouring as exposed group, and the other 709 auxiliary workers at the same factory, such as electricians, inspectors, fitters, and so on, as control group. Person-years of observation were calculated by persons observed and years followed-up for each of them. Person-year incidence of silicosis and its relative risk （RR） or odds ratio （OR） and 95% confidence intervals （CI） among the workers were estimated, adjusted for relevant factors with logistic regression model using SPSS version 15.0 software. Results Totally, 2 009 workers were followed-up for 37 151 person-years and 48 cases of silicosis were found, with an overall incidence of 1.34 per thousand, 2.02 per thousand in exposed group, and 0.15 per thousand in control one. Risk of silicosis was significantly higher in the exposed group than that in the control one （RR=13.13, 95% CI 3.18-54.13）, higher in men than that in women （RR=13.92, 95% CI 1.92-100.93）. Risks of silicosis varied by job, highest in those exposed to cast shakeout and finishing （RR=28.14, 95% CI 6.43-123.11）, followed by those exposed to pouring （RR-22.23, 95% CI 5.01-98.55） in the foundry. Average length of employment at onset of silicosis was 25.94 years, and silicosis incidence increased with length of employment. Average age at onset of silicosis was 47.83 years old. The risk of silicosis in workers with pulmonary tuberculosis was 2.57 folds as those without it （P〈0.01）. Ten deaths were recorded in those with silicosis, with a case-fatality rate of 20.83 percent three of them died of lung cancer, three of liver cancer, two of ischemic heart disease, and two of other diseases as their immediate causes of death. Incidence of silicosis in foundry workers positively correlated with their cumulative silica exposure （OR-3.00, 95% CI 2.34-3.83）. Risks of silicosis increased by 4.38 folds with an increase of 1 mg/m^3-year of cumulative silica exposure, and by 3.79 folds with smoking, respectively, adjusted for alcohol drinking and age. Based on a logistic regression model fitted, incidence of silicosis is expected to be 44.6 per thousand for those with daily exposure to silica of 4.18 mg/m^3 in average for 30 years, and if incidence of silicosis is expected to be less than 1 per thousand, daily exposure to silica should be controlled below 0.2 mg/m^3 for those with 20 years of employment, or below 0.1 mg/m^3 for those with 30 or 40 years of silica exposure. Conclusions At present, foundry workers in China still face high risk of developing silicosis. For lowering occurrence of silicosis in exposed workers, it seems necessary that current occupational exposure limits for silica at worksites in China should be reexamined and silica dust control measures be strengthend.展开更多
基金Supported by National Natural Science Foundation of China,No.81972255,No.81772597 and No.81672412Guangdong Natural Science Foundation,No.2017A030311002+4 种基金Guangdong Science and Technology Foundation,No.2017A020215196Fundamental Research Funds for the Central Universities of Sun YatSen University,No.17ykpy44Science Foundation of Jiangxi,No.20181BAB214002Education Department Science and Technology Foundation of Jiangxi,No.GJJ170936Grant from Guangdong Science and Technology Department,No.2017B030314026
文摘BACKGROUND Hepatocellular carcinoma(HCC)is a common cancer with a poor prognosis.Previous studies revealed that the tumor microenvironment(TME)plays an important role in HCC progression,recurrence,and metastasis,leading to poor prognosis.However,the effects of genes involved in TME on the prognosis of HCC patients remain unclear.Here,we investigated the HCC microenvironment to identify prognostic genes for HCC.AIM To identify a robust gene signature associated with the HCC microenvironment to improve prognosis prediction of HCC.METHODS We computed the immune/stromal scores of HCC patients obtained from The Cancer Genome Atlas based on the ESTIMATE algorithm.Additionally,a risk score model was established based on Differentially Expressed Genes(DEGs)between high and lowimmune/stromal score patients.RESULTS The risk score model consisting of eight genes was constructed and validated in the HCC patients.The patients were divided into high-or low-risk groups.The genes(Disabled homolog 2,Musculin,C-X-C motif chemokine ligand 8,Galectin 3,B-cell-activating transcription factor,Killer cell lectin like receptor B1,Endoglin and adenomatosis polyposis coli tumor suppressor)involved in our risk score model were considered to be potential immunotherapy targets,and they may provide better performance in combination.Functional enrichment analysis showed that the immune response and T cell receptor signaling pathway represented the major function and pathway,respectively,related to the immune-related genes in the DEGs between high-and low-risk groups.The receiver operating characteristic(ROC)curve analysis confirmed the good potency of the risk score prognostic model.Moreover,we validated the risk score model using the International Cancer Genome Consortium and the Gene Expression Omnibus database.A nomogram was established to predict the overall survival of HCC patients.CONCLUSION The risk score model and the nomogram will benefit HCC patients through personalized immunotherapy.
文摘Using the chronic obstructive pulmonary disease (COPD) medical records from January 1st to December 31st of 2013 and the Meteorological observation data, the air pollution data in the same time periods, generalized additive models were used to quantitatively analyze the relationship between COPD hospitalizations and temperature with controlling the confounding effects of time trend, meteorological factors and air pollution index (AQI). Results showed: variable temperature in 24 h (BT), 3d lagged minimum temperature (Tm3) and 5d lagged diurnal maximum temperature and minimum temperature range (Tc5) have different effects on COPD hospitalizations. When BT is between -4.4°C and -0.7°C, the relative risk (RR) increases to 1.0207 (95% CI: 1.0074 - 1.0342)with every 1°C increase in BT;when Tm3 is between -3.6°C and 3.2°C, the relative risk (RR) increases to 1.0118 (95% CI: 1.0015 - 1.0222)with every 1°C increase in Tm3, and when Tm3 is greater than 20.5°C, the relative risk (RR) increases to 1.0069 (95% CI: 1.0005 - 1.0133) with every 1°C increase in Tm3;when Tc5 is between 0.9°C and 8.6°C, if the Tc5 increases 1°C, the relative risk (RR) increases to 1.0125 (95% CI: 1.0066 - 1.0185. There are different effects for weather in different seasons on COPD hospitalizations: in autumn and winter, it is mainly of little BT and heavy air pollution weather;in spring, the large Tc5 weather is a main feature, and in summer, it’s mainly of high temperature and low pressure weather. The results help to provide some guidance on COPD forecasting services.
基金Supported by the National Natural Science Foundation of China,No.81801804
文摘BACKGROUND Hepatitis B virus (HBV) has been recognized as a leading cause of hepatocellular carcinoma (HCC). Numerous reports suggest that immune infiltration can predict the prognosis of HCC. Nonetheless, no creditable markers for prognosis of HBV-related HCC have been established by systematically assessing the immune-related markers based on tumor transcriptomes. AIM To establish an immune-related marker based on the cell compositions of immune infiltrate obtained based on tumor transcriptomes, so as to enhance the prediction accuracy of HBV-related HCC prognosis. METHODS RNA expression patterns as well as the relevant clinical data of HCC patients were obtained from The Cancer Genome Atlas. Twenty-two immunocyte fraction types were estimated by cell type identification by estimating relative subsets of RNA transcripts. Subsequently, the least absolute shrinkage and selection operator (LASSO) Cox regression model was employed to construct an immunoscore based on the immunocyte fraction types. Afterwards, the receiver operating characteristic (ROC) curve, Kaplan-Meier, and multivariate Cox analyses were performed. Additionally, a nomogram for prognosis that integrated the immunoscore as well as the clinical features was established. Meanwhile, the correlation of immunoscore with immune genes was also detected, and gene set enrichment analysis (GSEA) of the immunoscore was conducted. RESULTS A total of 22 immunocyte fraction types were predicted and compared among the tumor as well as non-tumor samples. An immunoscore was constructed through adopting the LASSO model, which contained eight immunocyte fraction types. Meanwhile, the areas under the ROC curves for the immunoscore biomarker prognostic model were 0.971, 0.912, and 0.975 for 1-, 3-, and 5-year overall survival (OS), respectively. Difference in OS between the high-immunoscore group and the low-immunoscore group was statistically significant [hazard ratio (HR)= 66.007, 95% confidence interval (CI): 8.361-521.105;P < 0.0001]. Moreover, multivariable analysis showed that the immunoscore was an independent factor for predicting the prognosis (HR = 2.997, 95%CI: 1.737-5.170). A nomogram was established, and the C-index was 0.757 (95%CI: 0.648-0.866). The immunoscore showed a significant negative correlation with the expression of PD-1 (P = 0.024), PD-L1 (P = 0.026), PD-L2 (P = 0.029), and CD27 (P = 0.033). Eight pathways were confirmed by GSEA. CONCLUSION The established immunoscore can potentially serve as a candidate marker to estimate the OS for HBV-related HCC cases.
文摘目的构建并验证一种头颈鳞状细胞癌(head and neck squamous cell carcinoma,HNSCC)自噬相关基因预后风险评分模型。方法从癌症基因组图谱(The Cancer Genome Atlas,TCGA)数据库下载全部HNSCC转录组表达数据(RNA sequencing,RNA-seq)及临床信息,筛选出差异表达基因,与GeneCards数据库检索的自噬相关基因(autophagy related genes,ARGs)取交集,得到差异表达的ARGs,整合临床信息后经预后分析获得预后相关的ARGs,再对其富集分析。应用套索(the least absolute shrinkage and selection operator,LASSO)回归和Cox回归模型构建一种用于预测HNSCC预后及生存情况的风险评分模型;绘制受试者工作特征(receiver operating characteristic,ROC)曲线,计算曲线下面积(area under the curve,AUC)及最佳截断(cut-off)值,并以最佳cut-off值将患者分为高、低风险评分组;绘制Kaplan-Meier生存曲线评价该模型的预测性能;将临床信息与风险评分对应整合,再次利用Cox回归分析评价风险评分的独立预后价值。结果通过对差异表达的ARGs进行预后分析初筛出20个与预后相关的ARGs,再应用LASSO回归和Cox回归分析获得9个与预后显著相关的ARGs,以此构建HNSCC的预后风险评分模型。ROC曲线及Kaplan-Meier生存曲线分析显示,低风险评分组生存时间优于高风险评分组,两组生存时间差异有统计学意义(P<0.001),且该模型在训练集(AUC最大值为0.69)与外部验证集(AUC最大值为0.822)中均展现出良好的预测性能。纳入临床信息后,对风险评分进行Cox回归分析,提示其与HNSCC患者预后显著相关(P<0.001),表明风险评分对HNSCC具有独立预后价值。结论由9个ARGs组成的HNSCC风险评分模型,可有效预测HNSCC患者的预后情况。
文摘Objectives The purposes were to determine the relationship between silicosis among foundry workers and their cumulative exposure to silica dust, and to establish a regression model to predict the risk for developing silicosis by a given length of employment and air concentrations of silica at worksites. Methods A 29-year cohort study was conducted, including all those employed for more than one year during January 1, 1980 to December 31, 1996 and all members of the cohort were followed-up to December 3 1, 2008. In total, 2 009 workers of an automobile foundry in Shiyan, Hubei province were recruited in the study, 1 300 at eight worksites including sand preparation, cast shakeout, and finishing, melting, moulding, core-making, overhead crane operation and pouring as exposed group, and the other 709 auxiliary workers at the same factory, such as electricians, inspectors, fitters, and so on, as control group. Person-years of observation were calculated by persons observed and years followed-up for each of them. Person-year incidence of silicosis and its relative risk （RR） or odds ratio （OR） and 95% confidence intervals （CI） among the workers were estimated, adjusted for relevant factors with logistic regression model using SPSS version 15.0 software. Results Totally, 2 009 workers were followed-up for 37 151 person-years and 48 cases of silicosis were found, with an overall incidence of 1.34 per thousand, 2.02 per thousand in exposed group, and 0.15 per thousand in control one. Risk of silicosis was significantly higher in the exposed group than that in the control one （RR=13.13, 95% CI 3.18-54.13）, higher in men than that in women （RR=13.92, 95% CI 1.92-100.93）. Risks of silicosis varied by job, highest in those exposed to cast shakeout and finishing （RR=28.14, 95% CI 6.43-123.11）, followed by those exposed to pouring （RR-22.23, 95% CI 5.01-98.55） in the foundry. Average length of employment at onset of silicosis was 25.94 years, and silicosis incidence increased with length of employment. Average age at onset of silicosis was 47.83 years old. The risk of silicosis in workers with pulmonary tuberculosis was 2.57 folds as those without it （P〈0.01）. Ten deaths were recorded in those with silicosis, with a case-fatality rate of 20.83 percent three of them died of lung cancer, three of liver cancer, two of ischemic heart disease, and two of other diseases as their immediate causes of death. Incidence of silicosis in foundry workers positively correlated with their cumulative silica exposure （OR-3.00, 95% CI 2.34-3.83）. Risks of silicosis increased by 4.38 folds with an increase of 1 mg/m^3-year of cumulative silica exposure, and by 3.79 folds with smoking, respectively, adjusted for alcohol drinking and age. Based on a logistic regression model fitted, incidence of silicosis is expected to be 44.6 per thousand for those with daily exposure to silica of 4.18 mg/m^3 in average for 30 years, and if incidence of silicosis is expected to be less than 1 per thousand, daily exposure to silica should be controlled below 0.2 mg/m^3 for those with 20 years of employment, or below 0.1 mg/m^3 for those with 30 or 40 years of silica exposure. Conclusions At present, foundry workers in China still face high risk of developing silicosis. For lowering occurrence of silicosis in exposed workers, it seems necessary that current occupational exposure limits for silica at worksites in China should be reexamined and silica dust control measures be strengthend.
