Objective Hepatocellular carcinoma(HCC)is sensitive to ferroptosis,a new form of programmed cell death that occurs in most tumor types.However,the mechanism through which ferroptosis modulates HCC remains unclear.This...Objective Hepatocellular carcinoma(HCC)is sensitive to ferroptosis,a new form of programmed cell death that occurs in most tumor types.However,the mechanism through which ferroptosis modulates HCC remains unclear.This study aimed to investigate the oncogenic role and prognostic value of FANCD2 and provide novel insights into the prognostic assessment and prediction of immunotherapy.Methods Using clinicopathological parameters and bioinformatic techniques,we comprehensively examined the expression of FANCD2 macroscopically and microcosmically.We conducted univariate and multivariate Cox regression analyses to identify the prognostic value of FANCD2 in HCC and elucidated the detailed molecular mechanisms underlying the involvement of FANCD2 in oncogenesis by promoting iron-related death.Results FANCD2 was significantly upregulated in digestive system cancers with abundant immune infiltration.As an independent risk factor for HCC,a high FANCD2 expression level was associated with poor clinical outcomes and response to immune checkpoint blockade.Gene set enrichment analysis revealed that FANCD2 was mainly involved in the cell cycle and CYP450 metabolism.Conclusion To the best of our knowledge,this is the first study to comprehensively elucidate the oncogenic role of FANCD2.FANCD2 has a tumor-promoting aspect in the digestive system and acts as an independent risk factor in HCC;hence,it has recognized value for predicting tumor aggressiveness and prognosis and may be a potential biomarker for poor responsiveness to immunotherapy.展开更多
To explore the impact of ursodeoxycholic acid(UDCA)on severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection and clinical outcomes in patients with autoimmune liver disease(AILD).Patients diagnosed with ...To explore the impact of ursodeoxycholic acid(UDCA)on severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection and clinical outcomes in patients with autoimmune liver disease(AILD).Patients diagnosed with AILD were enrolled and divided into a UDCA group and a non-UDCA group based on whether they received UDCA treatment.Relevant data were collected regarding AILD diagnosis,treatment,biochemical indicators,and imaging examination.The incidence of SARS-CoV-2 infection and the prognosis of AILD patients were observed.A total of 1,138 patients completed follow-up.The usage rate of hormone(P=0.003)and immunosuppressant(P=0.001)used for treating AILD in the non-UDCA group was markedly lower than in the UDCA group.The UDCA usage rate was markedly lower in SARS-CoV-2 infected patients than in uninfected patients(P=0.003).The rate of SARS-CoV-2 infection in the non-UDCA group was significantly higher than in the UDCA group(P=0.018).Logistic regression analysis showed that UDCA use(P=0.003)was correlated to a lower incidence of SARS-CoV-2,while immunosuppressant use(P=0.017)increased the incidence.Recovery time from SARS-CoV-2 infection was markedly longer for those receiving UDCA treatment than those in the non-UDCA group(P=0.018).UDCA is associated with low SARS-CoV-2 incidence in AILD patients,while immunosuppressant increases its incidence instead.Patients receiving UDCA treatment have a longer recovery time after being infected.展开更多
基金supported by Beijing Science and Technology Commission(grant number Z211100002921059)National Science and Technology Major Projects of China(2017ZX10201201-001-006,2017ZX10201201-002-006,and 2018ZX10715-005-003-005)+5 种基金Digestive Medical Coordinated Development Center of Beijing Hospital Authority(XXZ0302 and XXT28)National Key R&D Program China(2022YFC2603505)Beijing Hospital Authority Clinical Medicine Development with Special Funding Support(XMLX 202127)High-Level Public Health Technical Personnel Training Program of Beijing the Municipal Health Commission(2022-3-050)Capital Health Research and Development of Special(2022-1-2172)HBV infection,Clinical Cure and Immunology Joint Laboratory for Clinical Medicine Capital Medical University.
文摘Objective Hepatocellular carcinoma(HCC)is sensitive to ferroptosis,a new form of programmed cell death that occurs in most tumor types.However,the mechanism through which ferroptosis modulates HCC remains unclear.This study aimed to investigate the oncogenic role and prognostic value of FANCD2 and provide novel insights into the prognostic assessment and prediction of immunotherapy.Methods Using clinicopathological parameters and bioinformatic techniques,we comprehensively examined the expression of FANCD2 macroscopically and microcosmically.We conducted univariate and multivariate Cox regression analyses to identify the prognostic value of FANCD2 in HCC and elucidated the detailed molecular mechanisms underlying the involvement of FANCD2 in oncogenesis by promoting iron-related death.Results FANCD2 was significantly upregulated in digestive system cancers with abundant immune infiltration.As an independent risk factor for HCC,a high FANCD2 expression level was associated with poor clinical outcomes and response to immune checkpoint blockade.Gene set enrichment analysis revealed that FANCD2 was mainly involved in the cell cycle and CYP450 metabolism.Conclusion To the best of our knowledge,this is the first study to comprehensively elucidate the oncogenic role of FANCD2.FANCD2 has a tumor-promoting aspect in the digestive system and acts as an independent risk factor in HCC;hence,it has recognized value for predicting tumor aggressiveness and prognosis and may be a potential biomarker for poor responsiveness to immunotherapy.
基金the National Key Research and Development Program(2022YFC2603500,2022YFC2603505)Beijing Municipal Health Commission high-level public health technical personnel construction project,discipline leader-03-26,Beijing Hospitals Authority Clinical medicine Development of special funding support(XMLX 202127)+1 种基金the capital health research and development of special public health project(2022-1-2172)The Digestive Medical Coordinated Development Center of Beijing Hospitals Authority(XXZ0302).
文摘To explore the impact of ursodeoxycholic acid(UDCA)on severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection and clinical outcomes in patients with autoimmune liver disease(AILD).Patients diagnosed with AILD were enrolled and divided into a UDCA group and a non-UDCA group based on whether they received UDCA treatment.Relevant data were collected regarding AILD diagnosis,treatment,biochemical indicators,and imaging examination.The incidence of SARS-CoV-2 infection and the prognosis of AILD patients were observed.A total of 1,138 patients completed follow-up.The usage rate of hormone(P=0.003)and immunosuppressant(P=0.001)used for treating AILD in the non-UDCA group was markedly lower than in the UDCA group.The UDCA usage rate was markedly lower in SARS-CoV-2 infected patients than in uninfected patients(P=0.003).The rate of SARS-CoV-2 infection in the non-UDCA group was significantly higher than in the UDCA group(P=0.018).Logistic regression analysis showed that UDCA use(P=0.003)was correlated to a lower incidence of SARS-CoV-2,while immunosuppressant use(P=0.017)increased the incidence.Recovery time from SARS-CoV-2 infection was markedly longer for those receiving UDCA treatment than those in the non-UDCA group(P=0.018).UDCA is associated with low SARS-CoV-2 incidence in AILD patients,while immunosuppressant increases its incidence instead.Patients receiving UDCA treatment have a longer recovery time after being infected.
