Background:In many cancer types,aryl hydrocarbon receptor nuclear translocator 2(ARNT2)has been found to be associated with tumor cell proliferation and prognosis.However,the role of ARNT2 in clear cell renal cell car...Background:In many cancer types,aryl hydrocarbon receptor nuclear translocator 2(ARNT2)has been found to be associated with tumor cell proliferation and prognosis.However,the role of ARNT2 in clear cell renal cell carcinoma(ccRCC)has not been completely elucidated.In this study,the potential role of ARNT2 in ccRCC development was characterized.Methods:A pan-cancer dataset(TCGA-TARGET-GTEx)was accessed from UCSC Xena Data Browser.ARNT2 expression in normal and tumor samples was compared.Univariate Cox regression was performed to evaluate the prognostic value of ARNT2.Single sample gene set enrichment analysis(ssGSEA)was used to estimate the enrichment of functional pathways and gene signatures.CIBERSORT and ESTIMATE methods evaluated the immune infiltration.The ARNT2 expression was determined in ccRCC tissue and cell lines using RT-qPCR and Western blot.Results:ARNT2 expression was significantly dysregulated in 23 out of 30 cancer types.Pan-cancer data revealed a strong correlation between ARNT2 expression and immune modulators,immune cell infiltration,and genomic alternations.In ccRCC patients,the low-ARNT2 expression group had higher immune infiltration,CD8 T cells,and programmed cell death ligand 1 expression,as well as higher enrichment score of immunotherapeutic predictors than those in the high-ARNT2 expression group.Low-ARNT2 expression group was more responsive to immunotherapy.Moreover,low ARNT2 expression was observed in ccRCC tissue and cell lines.Conclusions:Dysregulated ARNT2 expression is involved in cancer development and the modulation of the immune microenvironment.ARNT2 can be potentially used as a prognostic indicator and an immunotherapeutic indicator for ccRCC.展开更多
目的探讨Toll样受体2(TLR2)、基质金属蛋白酶9(MMP-9)、低氧诱导因子1α(HIF-1α)作为免疫炎症因子与心房颤动(房颤)发生和维持的关系。方法入选125例房颤患者,其中阵发性房颤34例,持续性房颤49例,永久性房颤42例,选择窦性心律者38例作...目的探讨Toll样受体2(TLR2)、基质金属蛋白酶9(MMP-9)、低氧诱导因子1α(HIF-1α)作为免疫炎症因子与心房颤动(房颤)发生和维持的关系。方法入选125例房颤患者,其中阵发性房颤34例,持续性房颤49例,永久性房颤42例,选择窦性心律者38例作为对照组。比较各组患者血清中TLR2、MMP-9、HIF-1α的表达水平,同时测量左心房内径及射血分数。结果 TLR2表达水平在永久房颤组和持续房颤组明显高于对照组847.3(1 047.7)ng/L、757.2(1 032.5)ng/L vs 744.8(652.3)ng/L(P<0.05);永久房颤组TLR2高于阵发房颤组847.3(1 047.7)ng/L vs 796.6(849.1)ng/L(P<0.05)。MMP-9表达水平在永久房颤组明显高于对照组447.1(491.9)ng/L vs 308.9(200.7)ng/L(P<0.05);永久性房颤组和持续房颤组MMP-9高于阵发房颤组447.1(491.9)ng/L、307.7(678.0)ng/L vs 264.2(303.3)ng/L(P<0.05)。HIF-1α表达水平在永久房颤组和持续房颤组高于对照组57.2(48.8)ng/L、61.4(46.3)ng/L vs 46.7(29.6)ng/L(P<0.05);永久性房颤组和持续房颤组HIF-1α高于阵发房颤组57.2(48.8)ng/L、61.4(46.3)ng/L vs 52.5(42.8)ng/L(P<0.05)。永久房颤组和持续房颤组左心房内径较对照组和阵发性房颤组增加(45.70±6.71)mm、(42.67±6.83)mm vs(38.55±4.51)mm、(40.82±5.45)mm(P<0.05)。而持续房颤组左心室射血分数较对照组和阵发性房颤组明显降低(49.47±7.14)%vs(54.89±6.25)%、(53.90±8.02)%(P<0.05);永久性房颤组左心室射血分数较持续性房颤组明显降低(45.60±8.02)%vs(49.47±7.14)%(P<0.05)。结论 TLR2、HIF-1α、MMP-9作为免疫炎症因子水平的升高可能与房颤的发生及维持有关,提示炎症参与了房颤的发生与维持。展开更多
基金funded by the Shenzhen Longhua District Medical and Health Institutions Research Fund(Project No.2022102).
文摘Background:In many cancer types,aryl hydrocarbon receptor nuclear translocator 2(ARNT2)has been found to be associated with tumor cell proliferation and prognosis.However,the role of ARNT2 in clear cell renal cell carcinoma(ccRCC)has not been completely elucidated.In this study,the potential role of ARNT2 in ccRCC development was characterized.Methods:A pan-cancer dataset(TCGA-TARGET-GTEx)was accessed from UCSC Xena Data Browser.ARNT2 expression in normal and tumor samples was compared.Univariate Cox regression was performed to evaluate the prognostic value of ARNT2.Single sample gene set enrichment analysis(ssGSEA)was used to estimate the enrichment of functional pathways and gene signatures.CIBERSORT and ESTIMATE methods evaluated the immune infiltration.The ARNT2 expression was determined in ccRCC tissue and cell lines using RT-qPCR and Western blot.Results:ARNT2 expression was significantly dysregulated in 23 out of 30 cancer types.Pan-cancer data revealed a strong correlation between ARNT2 expression and immune modulators,immune cell infiltration,and genomic alternations.In ccRCC patients,the low-ARNT2 expression group had higher immune infiltration,CD8 T cells,and programmed cell death ligand 1 expression,as well as higher enrichment score of immunotherapeutic predictors than those in the high-ARNT2 expression group.Low-ARNT2 expression group was more responsive to immunotherapy.Moreover,low ARNT2 expression was observed in ccRCC tissue and cell lines.Conclusions:Dysregulated ARNT2 expression is involved in cancer development and the modulation of the immune microenvironment.ARNT2 can be potentially used as a prognostic indicator and an immunotherapeutic indicator for ccRCC.
文摘目的探讨Toll样受体2(TLR2)、基质金属蛋白酶9(MMP-9)、低氧诱导因子1α(HIF-1α)作为免疫炎症因子与心房颤动(房颤)发生和维持的关系。方法入选125例房颤患者,其中阵发性房颤34例,持续性房颤49例,永久性房颤42例,选择窦性心律者38例作为对照组。比较各组患者血清中TLR2、MMP-9、HIF-1α的表达水平,同时测量左心房内径及射血分数。结果 TLR2表达水平在永久房颤组和持续房颤组明显高于对照组847.3(1 047.7)ng/L、757.2(1 032.5)ng/L vs 744.8(652.3)ng/L(P<0.05);永久房颤组TLR2高于阵发房颤组847.3(1 047.7)ng/L vs 796.6(849.1)ng/L(P<0.05)。MMP-9表达水平在永久房颤组明显高于对照组447.1(491.9)ng/L vs 308.9(200.7)ng/L(P<0.05);永久性房颤组和持续房颤组MMP-9高于阵发房颤组447.1(491.9)ng/L、307.7(678.0)ng/L vs 264.2(303.3)ng/L(P<0.05)。HIF-1α表达水平在永久房颤组和持续房颤组高于对照组57.2(48.8)ng/L、61.4(46.3)ng/L vs 46.7(29.6)ng/L(P<0.05);永久性房颤组和持续房颤组HIF-1α高于阵发房颤组57.2(48.8)ng/L、61.4(46.3)ng/L vs 52.5(42.8)ng/L(P<0.05)。永久房颤组和持续房颤组左心房内径较对照组和阵发性房颤组增加(45.70±6.71)mm、(42.67±6.83)mm vs(38.55±4.51)mm、(40.82±5.45)mm(P<0.05)。而持续房颤组左心室射血分数较对照组和阵发性房颤组明显降低(49.47±7.14)%vs(54.89±6.25)%、(53.90±8.02)%(P<0.05);永久性房颤组左心室射血分数较持续性房颤组明显降低(45.60±8.02)%vs(49.47±7.14)%(P<0.05)。结论 TLR2、HIF-1α、MMP-9作为免疫炎症因子水平的升高可能与房颤的发生及维持有关,提示炎症参与了房颤的发生与维持。
