ObjectiveOctamer transcription factor 1(OCT1),a transcription factor that interacts with androgen receptor,is involved in prostate cancer(PCa)progression.The OCT1 target gene,Anillin actin-binding protein(ANLN),is hig...ObjectiveOctamer transcription factor 1(OCT1),a transcription factor that interacts with androgen receptor,is involved in prostate cancer(PCa)progression.The OCT1 target gene,Anillin actin-binding protein(ANLN),is highly expressed in castration-resistant PCa tissue;however,it remains unclear whether ANLN expression in hormone-sensitive PCa tissue could be used as a predictive biomarker for poor prognosis of patients.We aimed to investigate ANLN expression in PCa tissue obtained via radical prostatectomy and its correlation with clinical parameters.MethodsImmunohistochemical staining for ANLN was performed on 86 PCa specimens,followed by evaluation using immunoreactivity(IR)scores.Prognosis was analyzed by the log-rank test using the Kaplan–Meier method to generate a cancer-specific survival curve.The correlations between ANLN IR and clinical parameters as well as OCT1 IR were analyzed using the Chi-squared test.ResultsThe median IR score was 0 for ANLN.Accordingly,given the low median IR score,an IR score of≥3 was defined as positive.There were 17(19.8%)ANLN-positive cases,and these cases had a significantly poorer prognosis.Multivariate analysis revealed that the Gleason score,pathological tumor and lymph node stages,and positive ANLN expression were significant predictors of poor prognosis.Notably,patients with both positive ANLN and high OCT1 expression had a significantly decreased overall survival(p=0.001).ConclusionANLN,which is a OCT1 target gene especially in castration-resistant PCa,is expressed in a small number of hormone-sensitive PCa cases.Both positive ANLN expression and high OCT1 expression are significantly correlated with poor prognosis for PCa patients.展开更多
目的研究肌动蛋白结合蛋白(ANLN)、细胞色素P450(Cytochromes P 450,CYPs)亚家族成员CYP2C9、透明质酸介导运动因子受体(HMMR)在乙型肝炎病毒相关肝细胞癌(HBV-HCC)组织中的表达及对其预后的影响。方法收集手术切除的25份HCC标本。采用...目的研究肌动蛋白结合蛋白(ANLN)、细胞色素P450(Cytochromes P 450,CYPs)亚家族成员CYP2C9、透明质酸介导运动因子受体(HMMR)在乙型肝炎病毒相关肝细胞癌(HBV-HCC)组织中的表达及对其预后的影响。方法收集手术切除的25份HCC标本。采用免疫组织化学方法分析ANLN、CYP2C9、HMMR蛋白表达水平在癌组织及癌旁组织的差别,采用Log-Rank检验评估三者对HCC患者术后复发及远期存活的影响。结果HCC患者癌组织的ANLN、CYP2C9免疫反应性评分(IRS)低于癌旁组织分别为(2.4±2.5)分比(3.7±2.7)分(t=2.18,P=0.039)和(4.2±2.8)分比(8.6±1.4)分(t=6.21,P<0.01),癌组织中的HMMR IRS高于癌旁组织为8.0(4.0,8.0)分比4.0(2.5,4.0)分(Z=3.94,P<0.01)。但不同ANLN、CYP2C9、HMMR蛋白表达水平对HCC患者术后复发时间及5年存活率影响差异无统计学意义(中位复发时间高水平比低水平:ANLN 38.6月比33.3月,CYP2C936.5月比35.5月,HMMR 33.1月比41.3月;中位生存时间高水平比低水平:ANLN 56.3月比51.1月,CYP2C955.1月比51.5月,HMMR 53.0月比55.2月;均P>0.05)。多因素Cox回归分析提示,BCLC、家族史对术后复发时间的影响差异有统计学意义(HR=2.435,P=0.025;HR=0.165,P=0.009),AFP、家族史与术后5年存活率独立相关(HR=229.488,P=0.041;HR=0.054,P=0.014)。结论ANLN、CYP2C9、HMMR蛋白表达水平在HCC患者癌组织及癌旁组织存在差异,但对预后未产生影响,提示其可作为HCC诊断的潜在标志物。展开更多
Background: Anillin(ANLN) is required for tumor growth. It has been proven that knockdown of ANLN effectively reduces the occurrence of hepatocellular carcinoma(HCC) in transgenic mice. However, the functional role of...Background: Anillin(ANLN) is required for tumor growth. It has been proven that knockdown of ANLN effectively reduces the occurrence of hepatocellular carcinoma(HCC) in transgenic mice. However, the functional role of ANLN in HCC patients remains to be elucidated. Methods: Both microarray and TCGA project were used for the analyses of ANLN expression and regulation in HCC. The effect of ANLN on proliferation and cell cycle was detected by CCK-8, colony formation assay and flow cytometry. ANLN expression was measured by immunohistochemistry. Correlation between ANLN expression and clinicopathological features was assessed by Pearson Chi-square test and 5-year overall survival after liver resection was evaluated by Kaplan–Meier method. Results: Increased copy number, decreased methylation levels in the Cp G island and upregulated histone hypermethylation of ANLN were found in HCC. Knockdown of ANLN inhibited proliferation and induced G2/M phase arrest in SMMC-7721 cells. ANLN was mainly expressed in the nucleus and showed significantly higher expression levels in cancerous tissues than those in paired adjacent tissues. Moreover, nuclear ANLN expression levels in HCC metastases were significantly higher than those in primary HCC. The results of Cox proportional hazards regression model suggested that ANLN nuclear expression in HCC was an independent risk factor for poor 5-year overall survival of patients after liver resection. Conclusions: ANLN is a potential therapeutic target for HCC. Patients with nuclear ANLN overexpression in HCC tissue may need adjuvant therapy after liver resection.展开更多
基金supported by funding from Takeda Science Foundation,and JSPS KAKENHI(grant numbers JP19H03793 to Obinata D,JP20K07350 to Takayama K,JP19K09740 to Takahashi S,JP20K07875 to Hara M,and JP20K21667 and JP21H04829 to Inoue S).
文摘ObjectiveOctamer transcription factor 1(OCT1),a transcription factor that interacts with androgen receptor,is involved in prostate cancer(PCa)progression.The OCT1 target gene,Anillin actin-binding protein(ANLN),is highly expressed in castration-resistant PCa tissue;however,it remains unclear whether ANLN expression in hormone-sensitive PCa tissue could be used as a predictive biomarker for poor prognosis of patients.We aimed to investigate ANLN expression in PCa tissue obtained via radical prostatectomy and its correlation with clinical parameters.MethodsImmunohistochemical staining for ANLN was performed on 86 PCa specimens,followed by evaluation using immunoreactivity(IR)scores.Prognosis was analyzed by the log-rank test using the Kaplan–Meier method to generate a cancer-specific survival curve.The correlations between ANLN IR and clinical parameters as well as OCT1 IR were analyzed using the Chi-squared test.ResultsThe median IR score was 0 for ANLN.Accordingly,given the low median IR score,an IR score of≥3 was defined as positive.There were 17(19.8%)ANLN-positive cases,and these cases had a significantly poorer prognosis.Multivariate analysis revealed that the Gleason score,pathological tumor and lymph node stages,and positive ANLN expression were significant predictors of poor prognosis.Notably,patients with both positive ANLN and high OCT1 expression had a significantly decreased overall survival(p=0.001).ConclusionANLN,which is a OCT1 target gene especially in castration-resistant PCa,is expressed in a small number of hormone-sensitive PCa cases.Both positive ANLN expression and high OCT1 expression are significantly correlated with poor prognosis for PCa patients.
基金This study was supported by the grants from National Natural Science Foundation of China(81570590 and 81502509).
文摘Background: Anillin(ANLN) is required for tumor growth. It has been proven that knockdown of ANLN effectively reduces the occurrence of hepatocellular carcinoma(HCC) in transgenic mice. However, the functional role of ANLN in HCC patients remains to be elucidated. Methods: Both microarray and TCGA project were used for the analyses of ANLN expression and regulation in HCC. The effect of ANLN on proliferation and cell cycle was detected by CCK-8, colony formation assay and flow cytometry. ANLN expression was measured by immunohistochemistry. Correlation between ANLN expression and clinicopathological features was assessed by Pearson Chi-square test and 5-year overall survival after liver resection was evaluated by Kaplan–Meier method. Results: Increased copy number, decreased methylation levels in the Cp G island and upregulated histone hypermethylation of ANLN were found in HCC. Knockdown of ANLN inhibited proliferation and induced G2/M phase arrest in SMMC-7721 cells. ANLN was mainly expressed in the nucleus and showed significantly higher expression levels in cancerous tissues than those in paired adjacent tissues. Moreover, nuclear ANLN expression levels in HCC metastases were significantly higher than those in primary HCC. The results of Cox proportional hazards regression model suggested that ANLN nuclear expression in HCC was an independent risk factor for poor 5-year overall survival of patients after liver resection. Conclusions: ANLN is a potential therapeutic target for HCC. Patients with nuclear ANLN overexpression in HCC tissue may need adjuvant therapy after liver resection.
