α-L-岩藻糖苷酶对原发性肝癌诊断价值的探讨

探讨α－L－岩藻糖苷酶（alpha-L-fucosidase AFU)对原发性肝癌的诊断价值。分别采用放免法和显色多肽基质法对93例原发性肝癌、45例恶性肿瘤，98例良性肝病、46名孕产妇及20例正常健康人的血清中甲胎蛋白（alpha-fetoprotein AFP)水平和AFU活性进行联合检测。原发性肝癌组血清AFP水平及AFU活性明显高于其它各疾病组。AFU和AFP对原发性肝癌诊断的敏感性分别为76．3％和74．2％，在AFP阴性肝癌患者中AFU阳性率为75．0％。AFU，AFP两者联合检测诊断原发性肝癌的敏感性可提高到93．5％。     

检测血清α-L-岩藻糖苷酶对原发性肝癌的诊断意义

应用ELISA法检测了54例原发性肝癌和其他肝病患者血清α-L-岩藻糖苷酶(AFU)水平。结果显示原发性肝癌患者血清AFU浓度显著高于其他疾病组和对照组(P<0.01)。AFU对原发性肝癌的诊断敏感性为74.1％,特异性为98.8％,准确度为88.9％,且AFU水平与甲胎蛋白(AFP)及肝癌直径大小之间无相关性,提示血清AFU检测对原发性肝癌的诊断及鉴别诊断有一定价值,尤其对AFP阴性肝癌及小肝癌具有更重要的意义。     

血清α—l—岩藻糖苷酶对原发性肝癌诊断价值的进一步探讨

本文用显色多肽基质法检测血清α-L-岩藻糖苷酶(AFU)共167例,结果进一步证明AFU 检测对原发性肝癌(PHC)(72例)诊断敏感性及特异性分别达75. 0％及90. 5％;在 AFP 阴性或低滴度阳性 PHC 病例中的阳性率达83. 3％;AFU 与AFP 联合检测使诊断 PHC 的阳性率上升为93. 1％。且随病情好转和恶化而下降和上升。血清AFU 值 EdmondsonⅡ级肝癌明显高于Ⅲ级。PHC 肿瘤组织 AFU 含量明显低于非肿瘤组织,提示 AFU 为分泌型肝癌标志物。     

联合检测血清α-L-岩藻糖苷酶、甲胎蛋白对原发性肝癌患者的临床意义

探讨血清α-L-岩藻糖苷酶(AFU)和甲胎蛋白(AFP)的联合检测对原发性肝癌(PHC)诊断的临床意义.应用自动生化分析仪测定正常人,非PHC的其它恶性肿瘤组,PHC组患者血清AFU的含量,应用时间分辨荧光免疫分析测定血清AFP含量.PHC、肝转移癌、胰腺癌均高于正常对照组(P＜0.01或P＜0.05),PHC阳性率高90.9%.AFU与AFP之间无相关性(P＞0.5).血清AFU在PHC中敏感性较高.联合检测AFU、AFP对明显提高PHC的诊断具有实用价值.     

高尔基蛋白73、甲胎蛋白异质体3、甲胎蛋白和α-L-岩藻糖苷酶在肝脏疾病中的诊断价值

目的比较高尔基蛋白73(GP73)、甲胎蛋白异质体3(AFP-L3)、甲胎蛋白(AFP)和α-L-岩藻糖苷酶(AFU)在不同肝脏疾病患者中的意义及其单项或联合检测诊断肝癌的价值。方法对2013年1-12月收治的272例肝癌患者、203例肝硬化患者、248例慢性肝炎患者及210例健康体检者血清中的GP73、AFP-L3、AFP和AFU水平进行检测。非正态分布的数据多组间比较采用Kruskal-Wallis H检验,组间两两比较采用Mann-Whitney U检验,率的比较用卡方检验。ROC曲线绘制分别以健康人组和非肝癌组(健康体检、慢性肝炎、肝硬化)为对照。联合指标先进行Logistic拟合后再做ROC曲线。结果 GP73水平肝硬化组[177.0(116.0,247.0)ng/ml]较肝癌组[141.0(83.3,218.8)ng/ml])和慢性肝炎组[151.0(83.0,235.3)ng/ml]高(U=22 116.5、21 052.0,P均0.05);AFP-L3和AFP在肝癌组中的水平[11.3(4.3,21.2)%,78.4(7.1,2455.8)ng/ml]明显高于肝硬化组[6.0(4.0,8.0)%,10.0(3.8,49.5)ng/ml]和慢性肝炎组[7.0(5.0,9.0)%,18.8(4.4,79.6)ng/ml](P均0.05)。以健康人血清样本为对照绘制的诊断肝癌的ROC曲线,GP73、AFP-L3、AFP和AFU的ROC曲线下面积(AUC)分别为0.827、0.817、0.901和0.680。由此可知在鉴别健康人和肝癌患者方面,前3者比AFU有较高的准确性。以非肝癌患者血清样本为对照绘制的诊断肝癌的ROC曲线,4个指标对应的AUC分别为0.573、0.734、0.753和0.552,可见AFP-L3和AFP对于诊断肝癌有一定的准确性,其敏感性和特异性达到最大时的cut off值依次为8.55%(56.6%,84.9%),49.88 ng/ml(57.7%,80.9%)。结论 GP73的上升与肝损伤及长期纤维化有关,其在诊断肝脏疾病中有较好的敏感性,AFP-L3和AFP在诊断肝癌方面特异性较好,AFP-L3和AFP两者联合应用可提高肝癌的诊断敏感性至62.1%。     

血清高尔基蛋白73、甲胎蛋白异质体3、甲胎蛋白和α-L-岩藻糖苷酶水平诊断原发性肝癌的效能分析*

目的 探讨应用血清高尔基蛋白体73（GP73）、甲胎蛋白异质体3（AFP-L3）、AFP和α-L-岩藻糖苷酶（AFU）水平诊断原发性肝癌（PLC）患者的效能。方法 2015年1月~2017年3月我院诊治的PLC患者261例,乙型肝炎肝硬化患者201例,慢性乙型肝炎患者238例和体检健康人200例,采用酶联免疫吸附试验法检测血清GP73水平,采用亲和吸附离心管法检测血清AFP-L3,采用全自动化学发光仪检测血清AFP,采用商用试剂盒检测血清AFU水平。绘制血清GP73、AFP-L3、AFP和AFU诊断PLC的ROC曲线,确定截断点（cut-off-value）,计算ROC曲线下面积（AUC）,判断它们的诊断效能。结果 肝癌组血清GP73水平显著低于慢性肝炎组和肝硬化组,差异有统计学意义（P<0.05）,血清AFP-L3显著高于其他3组,差异有统计学意义（P<0.05）,血清AFU水平显著高于健康人和肝硬化组,但低于慢性肝炎组,差异有统计学意义（P<0.05）;以非肝癌人群为对照,血清GP73、AFP-L3、AFP和AFU诊断肝癌的ROC曲线下面积分别为0.564（95%CI：0.485~0.636）、0.724（95%CI：0.555~0.786）、0.745（95%CI：0.654~0.806）和0.571（95%CI：0.385~0.536）,血清AFP-L3联合AFP诊断肝癌的截断点分别为8.25%和49.25 ng/ml,其灵敏度（Se）为55.5%,特异度（Sp）为85.0%,正确性（Ac）为80.1%,显著高于血清AFP-L3诊断的55.5%、85.0%和76.4%或AFP诊断的57.1%、82.7%和75.2%（P<0.05）;在261例肝癌患者中,血清AFP<9.6 ng/ml者71例（27.2%),其中PG73>106.5 ng/ml者30例（42.3%）,提示GP73对AFP阴性肝癌有一定的诊断价值;在201例肝硬化患者中,血清AFP<9.6 ng/ml者98例（48.8%）,其中PG73>106.5 ng/ml者52例（53.1%）,提示血清GP73水平容易受到肝硬化的影响。结论 应用血清AFP联合AFP-L3检测能够提高诊断肝癌的效能,但它们的灵敏度都还不够高,影响因素较多。临床医生需结合病史、影像学检查和动态血清学检测才能做出更为科学的结论。     

血清高尔基蛋白73、甲胎蛋白异质体3、甲胎蛋白和α-L-岩藻糖苷酶水平诊断原发性肝癌的效能分析

目的探讨应用血清高尔基蛋白体73(GP73)、甲胎蛋白异质体3(AFP-L3)、AFP和α-L-岩藻糖苷酶(AFU)水平诊断原发性肝癌(PLC)患者的效能。方法 2015年1月～2017年3月我院诊治的PLC患者261例,乙型肝炎肝硬化患者201例,慢性乙型肝炎患者238例和体检健康人200例,采用酶联免疫吸附试验法检测血清GP73水平,采用亲和吸附离心管法检测血清AFP-L3,采用全自动化学发光仪检测血清AFP,采用商用试剂盒检测血清AFU水平。绘制血清GP73、AFP-L3、AFP和AFU诊断PLC的ROC曲线,确定截断点(cut-off-value),计算ROC曲线下面积(AUC),判断它们的诊断效能。结果肝癌组血清GP73水平显著低于慢性肝炎组和肝硬化组,差异有统计学意义(P0.05),血清AFP-L3显著高于其他3组,差异有统计学意义(P0.05),血清AFU水平显著高于健康人和肝硬化组,但低于慢性肝炎组,差异有统计学意义(P0.05);以非肝癌人群为对照,血清GP73、AFP-L3、AFP和AFU诊断肝癌的ROC曲线下面积分别为0.564 (95%CI:0.485～0.636)、0.724 (95%CI:0.555～0.786)、0.745(95%CI:0.654～0.806)和0.571(95%CI:0.385～0.536),血清AFP-L3联合AFP诊断肝癌的截断点分别为8.25%和49.25 ng/ml,其灵敏度(Se)为55.5%,特异度(Sp)为85.0%,正确性(Ac)为80.1%,显著高于血清AFP-L3诊断的55.5%、85.0%和76.4%或AFP诊断的57.1%、82.7%和75.2%(P0.05);在261例肝癌患者中,血清AFP9.6 ng/ml者71例(27.2%),其中PG73106.5 ng/ml者30例(42.3%),提示GP73对AFP阴性肝癌有一定的诊断价值;在201例肝硬化患者中,血清AFP9.6 ng/ml者98例(48.8%),其中PG73106.5 ng/ml者52例(53.1%),提示血清GP73水平容易受到肝硬化的影响。结论应用血清AFP联合AFP-L3检测能够提高诊断肝癌的效能,但它们的灵敏度都还不够高,影响因素较多。临床医生需结合病史、影像学检查和动态血清学检测才能做出更为科学的结论。     

肝癌患者血清AFP、AFU和SHCSP的联合检测

为探讨多种肝癌标志物联合检测对原发性肝癌的临床诊断价值。对79例经B超、计算机断层扫描(CT)诊断为肝癌的患者进行了甲胎蛋白(AFP)、α-L-岩藻糖苷酶(AFU)和特异性肝癌蛋白(SHCSP)的联合检测。单项AFP、AFU和SHCSP法在PHC组的阳性检出率分别为75．95％、72．15％及70．89％，AFP法与AFU法两项联检阳性率为91．14％，AFP法与SHCSP法两项联检，阳性率为89．87％，三项联检的阳性率97．47％，均显著高于任何单项检测的阳性率(χ^2＝15．87，P＜0．005)。AFU法和SHCSP法在19例AFP阴性的PHC病例中，阳性检出率分别为73．6％和68．42％。采用多种肿瘤标志物联合检测，可明显提高肝癌患者的诊断率，对肝癌的早期诊断，尤其对AFP阴性的肝癌诊断具有更重要的临床应用价值。     

联合检测血清AFP、AFU和ALP对原发性肝癌诊断的价值

目的探讨肿瘤标志物甲胎蛋白(AFP)、α-L-岩藻糖苷酶(AFU)和碱性磷酸酶(ALP)对原发性肝癌(PHC)联合检测的诊断价值。方法收集本院消化内科2014年2月至2016年2月期间住院的67例PHC患者、56例良性肝病以及同期60例健康体检者血清,常规方法检测其血清AFP、AFU和ALP含量。分析联合检测AFP、AFU、ALP对PHC的诊断价值。结果 PHC组的AFP平均水平为(328.6±198.5)ng/mL、AFU为(68.3±7.4)U/L、ALP为(256.3±77.2)U/L,明显高于良性肝病组和对照组,差异有统计学意义(P0.05)。对于PHC患者,AFP、AFU和ALP的检测阳性率分别为67.16%、73.13%和71.64%,其中AFU的敏感度最高,而AFP的特异度最高,3项指标联合检测其敏感度可达88.06%,阴性预测值提高至89.74%。结论联合检测血清AFP、AFU和ALP可以提高PHC诊断敏感度,对于PHC的诊断和病情监测具有较大的临床价值。     

多种肿瘤标志物对发性肝癌的诊断价值

目的：探讨血清甲胎蛋白（AFP）、α－L－岩藻糖苷酶（AFU）、r-谷氨酰转肽酶（GGT）、血清糖抗原19－9（CA19－9）对原发性肝癌的诊断价值。方法对59例原发性肝癌（PHC）、47例良性肝病及41名正常人进行AFP、AFU、GGT、CA19－9的同步测定和对照。结果：AFP、AFU、GGT、CA19－9对PHC诊断的敏感性依次为76．3％、84．7％、66．1％和67．8％,特异性为85．2％、88．6％、56．8％和80．6％。联合检测对PHC诊断的敏感性可提高为94．9％。结论多种肿瘤标志物联合检测对诊断PHC具有重要价值。     

Characterization of Two Unique α-Globin Gene Cluster Deletions Causing α-Thalassemia in Israeli Arabs

The molecular basis of α-thalassemia (α-thal) is complex. The use of multiplex ligation-dependent probe amplification (MLPA) has offered the possibility of identifying more gene deletions causing α-thal. Our objective was to determine the molecular basis of two patients with Hb H (β4) disease. By using MLPA in combination with comparative genomic hybridization (CGH) we identified two novel α-globin gene cluster deletions: a 30?kb deletion (patient 1) we refer to as – –^JAL and a large 216?kb deletion (patient 2) we refer to as – –^LOD. Patient 1 was a compound heterozygote for – –^JAL and –α^3.7 (rightward deletion). Twelve family members of patient 1 carrying the – –^JAL deletion were available for evaluation: five with – –^JAL/–α^3.7, four with – –^JAL/α^{Hph I}α and three with – –^JAL/αα. Their clinical picture of compound heterozygosity was compatible with moderate Hb H disease. In patient 2 (– –^LOD/–α^3.7), no additional symptoms were present despite the heterozygous deletion of seven known genes, three non coding RNAs (ncRNAs), four unknown genes and two pseudo genes. Further analysis of more patients with α-thal deletions will have implications for genetic counseling and appropriate therapy.     

Spectrum of Common α-Globin Deletion Mutations in the Southern Region of Vietnam

The common deletion mutations of α-globin genes in the Vietnamese population is not well known. Here we report the presence of five deletional mutations of Southeast Asia in the southern region of Vietnam. The – –^SEA (NG_000006.1: g.26264_45564del19301) mutation is the most common type of deletion (87.35%), followed by the –α^3.7 (rightward) (NG_000006.1: g.34164_37967del3804) deletion (9.64%), –α^4.2 (leftward) (AF221717) deletion (2.41%) and – –^THAI (NG_000006.1: g.10664_44164del33501) (0.6%) mutation in this region. The – –^FIL (NG_000006.1: g.11684_43534del31581) mutation was not detected in this study. This result provided a view of the distribution of common α-globin gene mutations in Vietnam and could serve as a baseline for further investigations into these genetic defects.     

Detection of Hb-Papio B,a Silent Mutation of the Baboon β Chain,by High Performance Liquid Chromatography. Improved Procedures for the Separation of Globin Chains by Hplc

A silent mutant of the β chain of the baboon (Papio cynocephalus) was detected by high performance liquid chromatography of the globin chains. The substitution is β13 Ala → Thr. The inclusion of nonylamine in the developers for HPLC results not only in an improved separation of baboon globin chains but also in the complete resolution of the human G_γ, A_γ, and A_γT chains and some common human variant β chains.     

Identification of a Novel 9.7 kb Deletion Causing α0-Thalassemia in Two Pregnant Women in Southern China

Abstract

The technique of combining multiplex ligation-dependent probe amplification (MLPA), array comparative genomic hybridization (CGH) and gap-polymerase chain reaction (gap-PCR) is an effective way to locate unknown breakpoints on the α-globin genes. In the current report, a novel deletion was detected in two pregnant women with moderate hematological phenotypes. Multiplex ligation-dependent probe amplification and array CGH revealed a probable 9.7?kb deletion at 16p13.3. The breakpoints were precisely defined by gap-PCR and direct sequencing. This deletion (NG_000006.1: g.32709_42418del) included HBA1, HBA2 and HBQ, which resulted in an α⁰-thalassemia (α⁰-thal) mutation. There would be a 25.0% chance of conceiving an α-thal intermedia or α-thal major (α-TI or α-TM) fetus if the couples are both carriers. Rare large deletions can cause α-thalassemia (α-thal) and the structure analysis of an unknown deletion is important for clinical diagnosis and further genetic counseling.     

A Novel α-Thalassemia Nonsense Mutation on the α2-Globin Gene: HBA2: c.184A>T

We report a novel mutation on the α2-globin gene, HBA2: c.184A>T, detected in a Chinese proband. This mutation resulted in a Lys→Term substitution at position 62 of the α2-globin gene, causing a premature termination of translation. This mutation did not cause severe hematological abnormalities in the carriers. From the properties of substituted residues on the α2-globin gene, it is generally expected that this mutation causes unstable and truncated protein, thus this mutation should be detected in couples at-risk for α-thalassemia (α-thal).     

Quintuple α-Globin Gene: A Novel Allele in a Sudanese Man

Multiple α-globin repeats have previously been discovered in humans and other mammals. A quintuple α-globin gene (αα/ααααα) was found in a Sudanese male undergoing evaluation for microcytosis.     

α-Thalassemia Caused by Two Novel Splice Mutations of the α2-Globin Gene: IVS-I-1 (G>A and G>T)

We report the identification of two different mutations involving the first nucleotide of intron 1 of the α2-globin gene: IVS-I-1 G→A and G→T. The available data indicated that both mutations reduce the efficiency of proper mRNA splicing, resulting in α⁺-thalassemia (α⁺-thal).     

Codon 62 (GTG>GCG,Val→Ala) (α1) (HBA1: c.188T>C) Causing Nondeletional α-Thalassemia in a Chinese Family

We report a novel α-globin gene point mutation detected during newborn screening for hemoglobinopathies. Sequence analyses identified a GTG>GCG substitution at codon 62 of the α1-globin gene. This mutation causes a silent α-thalassemia (α-thal).     

The Molecular Basis of α-Thalassemia in the Qatari Pediatric Population

Abstract

α-Thalassemia (α-thal) is widely reported in the Arabian Peninsula as one of the main causes of asymptomatic microcytic hypochromic red blood cells with or without anemia in the pediatric population. This is the first study that provides information about the molecular basis of α-thal in the Qatari population. Qatari school children between the ages of 5 and 15, exhibiting laboratory findings suggestive of microcytic anemia were pooled, and those with a mean corpuscular volume (MCV) of <80.0?fL and a hemoglobin (Hb) electropherogram that ruled out β-thalassemia (β-thal), were narrowed down to a group of 127. This group was screened for the ?α^3.7 (rightward) deletion, and the α^?5?nt, α^polyA1 (α^T-Saudi), α^polyA2 mutations. A second group of randomly selected Qatari individuals was also screened in order to determine the population’s allele frequency for the ?α^3.7 deletion. Thirty-nine point four percent of the individuals with microcytic hypochromic anemia were positive for the ?α^3.7 deletion (heterozygotes 30.0%, homozygotes 9.4%), 2.6% were positive for the α^polyA1 deletion and 0.8% positive for the α^?5?nt mutation. None of the children exhibited changes in α^polyA2. Analysis of the random samples determined that 26.4% were heterozygous and 4.5% homozygous for the ?α^3.7 deletion with a 17.7% allele frequency. Our results suggest that a significant number of the Qatari pediatric population with microcytic hypochromic anemia are carriers of α-thal mutations. However, 45.6% of the children failed to exhibit any of the above four mutations tested. This suggests the possibility of other mutations in the Qatari pediatric population that are yet to be elicited.     

Coinheritance of α-Thalassemia Decreases the Risk of Cerebrovascular Disease in a Cohort of Children with Sickle Cell Anemia

The study estimated α-thalassemia (α-thal) prevalence and assessed its associations with clinical and hematological features in a random sample of Brazilian children with sickle cell anemia (208 Hb SS and 13 Hb S-β⁰-thal). α-Thalassemia genotyping was carried out by multiplex polymerase chain reaction (m-PCR) for seven alleles. Clinical and hematological data were retrieved from the 221 children's medical files. Their ages ranged from 2.5 to 10.4 years. Of the Hb SS children, 27.9% carried –α^3.7/αα and 1.4% –α^3.7/–α^3.7. The presence of α-thal was significantly associated with reduction in MCV, MCH, WBC values and reticulocyte counts. No significant association with blood transfusion or acute chest syndrome (ACS), was found. α-Thalassemia genotypes were strongly associated with reduction in risk for cerebrovascular disease (CVD) (conditional and abnormal transcranial Doppler or stroke; p = 0.007). The interaction of α-thal with other modulating factors should be investigated in order to define subphenotypes of the disease and to use them as clinical tools in the follow-up care of patients.