目的探讨CCDC8和TGF-β1在非小细胞肺癌中的表达及其与临床病理特征的关系。方法比较TCGA数据库正常肺组织与肿瘤组织中CCDC8和TGF-β1的表达量,分析非小细胞肺癌中CCDC8和TGF-β1表达的相关性。免疫组织化学染色检测204例常规石蜡包埋...目的探讨CCDC8和TGF-β1在非小细胞肺癌中的表达及其与临床病理特征的关系。方法比较TCGA数据库正常肺组织与肿瘤组织中CCDC8和TGF-β1的表达量,分析非小细胞肺癌中CCDC8和TGF-β1表达的相关性。免疫组织化学染色检测204例常规石蜡包埋非小细胞肺癌组织CCDC8、TGF-β1表达并分析其与肺癌临床病理特征关系。利用Kaplan-Meier法绘制生存曲线,应用Cox回归分析CCDC8、TGF-β1表达与患者总生存期(OS)的关系。结果TCGA数据中正常肺组织CCDC8与TGF-β1表达较肿瘤组织中高( P <0.05),非小细胞肺癌患者CCDC8表达与TGF-β1表达呈正相关( P <0.0001);鳞癌中CCDC8低表达患者OS长( HR =1.32, P =0.0437)。204例非小细胞肺癌组织中,CCDC8表达与TGF-β1表达呈正相关( P =0.023)。Cox单因素分析鳞癌中CCDC8表达与OS有关( P =0.013);而CCDC8和TGF-β1表达与腺癌患者生存无关( P =0.967, P =0.816)。Cox多因素分析TNM分期、CCDC8表达是肺鳞癌患者预后因子( P = 0.016)。结论非小细胞肺癌中CCDC8表达与TGF-β1表达正相关,CCDC8可能是肺鳞癌患者预后因子。展开更多
BACKGROUND A rare autosomal recessive genetic disorder,3M syndrome,is characterized by severe intrauterine and postnatal growth retardation.Children with 3M syndrome typically exhibit short stature,facial deformities,...BACKGROUND A rare autosomal recessive genetic disorder,3M syndrome,is characterized by severe intrauterine and postnatal growth retardation.Children with 3M syndrome typically exhibit short stature,facial deformities,long tubular bones,and high vertebral bodies but generally lack mental abnormalities or other organ damage.Pathogenic genes associated with 3M syndrome include CUL7,OBSL1 and CCDC8.The clinical and molecular characteristics of patient with 3M syn-drome are unique and serve as important diagnostic indicators.CASE SUMMARY In this case,the patient displayed square shoulders,scoliosis,long slender tubular bones,and normal neurological development.Notably,the patient did not exhibit the typical dysmorphic facial features,relative macrocephaly,or growth retardation commonly observed in individuals with 3M syndrome.Whole exon sequencing revealed a novel heterozygous c.56681+1G>C(Splice-3)variant and a previously reported nonsense heterozygous c.3341G>A(p.Trp1114Ter)variant of OBSL1.Therefore,it is important to note that the clinical features of 3M syndrome may not always be observable,and genetic confirmation is often required.Additionally,the identification of the c.5683+1G>C variant in OBSL1 is notewor-thy because it has not been previously reported in public databases.CONCLUSION Our study identified a new variant(c.5683+1G>C)of OBSL1 that contributes to expanding the molecular profile of 3M syndrome.展开更多
文摘卷曲螺旋结构蛋白8(coiled-coil domain containing 8,CCDC8)是一个由CCDC8基因编码目前功能未知的蛋白质。已有的证据表明,CCDC8是一个膜蛋白,与细胞骨架蛋白Obsl1(Obscurin-like protein1)、泛素E3连接酶Cul7(Cullin 7)在一个信号通路。CCDC8、Obsl1或者Cul7基因突变可以引起身材矮小的3-M综合征(3M syndrome)。CCDC8与锚蛋白ANKRA2(ankyrin-repeat family A protein 2)、p53通路相关的细胞凋亡有关;CCDC8与乳腺癌、肺癌等癌症有关;CCDC8还可与艾滋病毒(HIV-1)结构蛋白Gag相互作用,诱导Gag的内化、多泛素化和降解。
文摘目的探讨CCDC8和TGF-β1在非小细胞肺癌中的表达及其与临床病理特征的关系。方法比较TCGA数据库正常肺组织与肿瘤组织中CCDC8和TGF-β1的表达量,分析非小细胞肺癌中CCDC8和TGF-β1表达的相关性。免疫组织化学染色检测204例常规石蜡包埋非小细胞肺癌组织CCDC8、TGF-β1表达并分析其与肺癌临床病理特征关系。利用Kaplan-Meier法绘制生存曲线,应用Cox回归分析CCDC8、TGF-β1表达与患者总生存期(OS)的关系。结果TCGA数据中正常肺组织CCDC8与TGF-β1表达较肿瘤组织中高( P <0.05),非小细胞肺癌患者CCDC8表达与TGF-β1表达呈正相关( P <0.0001);鳞癌中CCDC8低表达患者OS长( HR =1.32, P =0.0437)。204例非小细胞肺癌组织中,CCDC8表达与TGF-β1表达呈正相关( P =0.023)。Cox单因素分析鳞癌中CCDC8表达与OS有关( P =0.013);而CCDC8和TGF-β1表达与腺癌患者生存无关( P =0.967, P =0.816)。Cox多因素分析TNM分期、CCDC8表达是肺鳞癌患者预后因子( P = 0.016)。结论非小细胞肺癌中CCDC8表达与TGF-β1表达正相关,CCDC8可能是肺鳞癌患者预后因子。
文摘BACKGROUND A rare autosomal recessive genetic disorder,3M syndrome,is characterized by severe intrauterine and postnatal growth retardation.Children with 3M syndrome typically exhibit short stature,facial deformities,long tubular bones,and high vertebral bodies but generally lack mental abnormalities or other organ damage.Pathogenic genes associated with 3M syndrome include CUL7,OBSL1 and CCDC8.The clinical and molecular characteristics of patient with 3M syn-drome are unique and serve as important diagnostic indicators.CASE SUMMARY In this case,the patient displayed square shoulders,scoliosis,long slender tubular bones,and normal neurological development.Notably,the patient did not exhibit the typical dysmorphic facial features,relative macrocephaly,or growth retardation commonly observed in individuals with 3M syndrome.Whole exon sequencing revealed a novel heterozygous c.56681+1G>C(Splice-3)variant and a previously reported nonsense heterozygous c.3341G>A(p.Trp1114Ter)variant of OBSL1.Therefore,it is important to note that the clinical features of 3M syndrome may not always be observable,and genetic confirmation is often required.Additionally,the identification of the c.5683+1G>C variant in OBSL1 is notewor-thy because it has not been previously reported in public databases.CONCLUSION Our study identified a new variant(c.5683+1G>C)of OBSL1 that contributes to expanding the molecular profile of 3M syndrome.
