BACKGROUND:Hepatocellular carcinoma(HCC)is a highly malignant tumor with a poor prognosis.Because small HCCs possess most of the characteristics of early HCC,we investigated small HCCs to screen potential biomarkers f...BACKGROUND:Hepatocellular carcinoma(HCC)is a highly malignant tumor with a poor prognosis.Because small HCCs possess most of the characteristics of early HCC,we investigated small HCCs to screen potential biomarkers for early diagnosis.METHODS:Proteins were extracted from 10 sets of paired tissue samples from HBV-infected small-HCC patients.The extracted proteins were well resolved by two-dimensional electrophoresis.These HCC-associated proteins were then identified by MALDI-TOF/TOF MS following image analysis.Western blotting and immunohistochemistry were used to assess glutamine synthetase(GS)and phenazine biosynthesislike domain-containing protein(PBLD)expression in liver tissue.Enzyme-linked immunosorbent assays in 152 serum samples(from 49 healthy donors,24 patients with liver cirrhosis,and 79 with HCC)were used to further assess the significance of GS clinically.RESULTS:Fifteen up-regulated and three down-regulated proteins were identified.Western blotting confirmed GS overexpression and decreased PBLD expression in liver tissue.Immunohistochemistry showed that GS was expressed in 70.0%(84/120)of HCCs and 35.8%(43/120)of nontumor tissues;PBLD was expressed in 74.2%(89/120) of nontumor tissues and 40.8%(49/120)of HCCs.The Chi-square test showed significant expression differences between HCCs and adjacent tissues.Consistent with this,serum GS levels in HCC patients were significantly higher than those in liver cirrhosis patients and healthy donors,while the latter two groups were also significantly different.In addition, a diagnostic cutoff value of 2.6 mg/ml was used for GS;it was elevated in 19(76.0%)of 25 HCC patients with AFP≤20 ng/ml and 47(88.7%)of 53 HCC patients with AFP≤200 ng/ml.CONCLUSION:GS and PBLD are abnormally expressed in most HCCs.GS may be a novel serum marker for early HCC, especially for those patients with low AFP levels(≤200 ng/ml).展开更多
目的:采用倾向性评分匹配分析女性乳腺化生乳腺癌(metaplastic breast cancer,MBC)患者的临床病理特征和生存结局,并探讨预后相关因素。方法:在监测、流行病学与最终结果(Surveillance,Epidemiology and End Results,SEER)数据中收集201...目的:采用倾向性评分匹配分析女性乳腺化生乳腺癌(metaplastic breast cancer,MBC)患者的临床病理特征和生存结局,并探讨预后相关因素。方法:在监测、流行病学与最终结果(Surveillance,Epidemiology and End Results,SEER)数据中收集2010—2015年1473例MBC患者和233425例非特殊类型浸润性导管癌(invasive ductal carcinoma,IDC)患者的临床病理资料,采用倾向性评分匹配排除基线特征的选择偏倚,比较MBC与IDC患者的临床病理学特征,采用Kaplan Meier法和log-rank法进行生存分析和检验,采用COX比例回归模型分析MBC患者预后的独立危险因素。结果:MBC的组织学分级以G_(3)居多;T_(2)和T_(3)分期多见;腋窝淋巴结转移较少;临床分期偏晚,确诊时Ⅱ~Ⅳ期患者所占比例高于IDC患者;激素受体表达阳性率低,73.59%的MBC患者激素受体阴性,分子分型以三阴性乳腺癌为主。单因素分析显示,肿瘤大小、区域淋巴结转移、远处转移和临床分期均是影响BCSS和OS的独立危险因素,手术和局部放疗是OS的保护因素。多因素分析结果显示,年龄、组织学分级、肿瘤分期、手术、化疗和放疗是影响BCSS和OS的独立危险因素(P<0.05)。结论:MBC是一种较为罕见且组织学分级高以及激素受体阳性率低的亚类疾病,其预后较IDC差,手术、化疗和放疗可能助于改善预后。展开更多
基金supported by a grant from the Beijing Municipal Science and Technology Commission(No.Z0006264040791)
文摘BACKGROUND:Hepatocellular carcinoma(HCC)is a highly malignant tumor with a poor prognosis.Because small HCCs possess most of the characteristics of early HCC,we investigated small HCCs to screen potential biomarkers for early diagnosis.METHODS:Proteins were extracted from 10 sets of paired tissue samples from HBV-infected small-HCC patients.The extracted proteins were well resolved by two-dimensional electrophoresis.These HCC-associated proteins were then identified by MALDI-TOF/TOF MS following image analysis.Western blotting and immunohistochemistry were used to assess glutamine synthetase(GS)and phenazine biosynthesislike domain-containing protein(PBLD)expression in liver tissue.Enzyme-linked immunosorbent assays in 152 serum samples(from 49 healthy donors,24 patients with liver cirrhosis,and 79 with HCC)were used to further assess the significance of GS clinically.RESULTS:Fifteen up-regulated and three down-regulated proteins were identified.Western blotting confirmed GS overexpression and decreased PBLD expression in liver tissue.Immunohistochemistry showed that GS was expressed in 70.0%(84/120)of HCCs and 35.8%(43/120)of nontumor tissues;PBLD was expressed in 74.2%(89/120) of nontumor tissues and 40.8%(49/120)of HCCs.The Chi-square test showed significant expression differences between HCCs and adjacent tissues.Consistent with this,serum GS levels in HCC patients were significantly higher than those in liver cirrhosis patients and healthy donors,while the latter two groups were also significantly different.In addition, a diagnostic cutoff value of 2.6 mg/ml was used for GS;it was elevated in 19(76.0%)of 25 HCC patients with AFP≤20 ng/ml and 47(88.7%)of 53 HCC patients with AFP≤200 ng/ml.CONCLUSION:GS and PBLD are abnormally expressed in most HCCs.GS may be a novel serum marker for early HCC, especially for those patients with low AFP levels(≤200 ng/ml).
文摘目的:采用倾向性评分匹配分析女性乳腺化生乳腺癌(metaplastic breast cancer,MBC)患者的临床病理特征和生存结局,并探讨预后相关因素。方法:在监测、流行病学与最终结果(Surveillance,Epidemiology and End Results,SEER)数据中收集2010—2015年1473例MBC患者和233425例非特殊类型浸润性导管癌(invasive ductal carcinoma,IDC)患者的临床病理资料,采用倾向性评分匹配排除基线特征的选择偏倚,比较MBC与IDC患者的临床病理学特征,采用Kaplan Meier法和log-rank法进行生存分析和检验,采用COX比例回归模型分析MBC患者预后的独立危险因素。结果:MBC的组织学分级以G_(3)居多;T_(2)和T_(3)分期多见;腋窝淋巴结转移较少;临床分期偏晚,确诊时Ⅱ~Ⅳ期患者所占比例高于IDC患者;激素受体表达阳性率低,73.59%的MBC患者激素受体阴性,分子分型以三阴性乳腺癌为主。单因素分析显示,肿瘤大小、区域淋巴结转移、远处转移和临床分期均是影响BCSS和OS的独立危险因素,手术和局部放疗是OS的保护因素。多因素分析结果显示,年龄、组织学分级、肿瘤分期、手术、化疗和放疗是影响BCSS和OS的独立危险因素(P<0.05)。结论:MBC是一种较为罕见且组织学分级高以及激素受体阳性率低的亚类疾病,其预后较IDC差,手术、化疗和放疗可能助于改善预后。
