The response of Golgi protein 73 to transcatheter arterial chemoembolization in patients with hepatocellular carcinoma may relate to the influence of certain chemotherapeutics

BACKGROUND： Golgi protein 73 （GP73） is a promising bio- marker of hepatocellular carcinoma （HCC）. It decreases after surgical resection, and resumes upon recurrence, indicating a potential indicator for the effectiveness of the treatment. But changes of GP73 after transcatheter arterial chemoemboliza- tion （TACE） have not been reported so far. This study was to investigate the dynamic changes of GP73 in HCC patients af- ter TACE treatment, and the possible underlying mechanisms in the cell cultures. METHODS： Blood samples were collected from 72 HCC pa- tients, before TACE, at day I and day 30 after TACE. GP73 lev- els were measured by Western blotting. The dynamic changes of GP73 were analyzed and compared with image changes and clinical data. The effects of chemotherapeutic agents （5-FU and pirarubicin） on GP73 expression were tested in three HCC cell lines （HepG2, HCCLM3 and MHCC97H）. RESULTS： The GP73 level was significantly elevated at day 1 and day 30 after TACE in HCC patients compared with that before the procedure （P〈0.05）. There was no statistical differ- ence between the two time points after TACE, nor correlationbetween GP73 levels and dinicopathological features, tumor metastasis, and patient survival. Pirarubicin, not 5-FU, signifi- cantly increased GP73 expression in three cell lines. CONCLUSIONS： Unlike surgical resection which decreases the GP73 level, TACE significantly increased GP73 expression in patients with HCC. No correlations were observed among GP73 levels, tumor characteristics and prognosis of patients with HCC.

Effects of microwave ablation on serum Golgi protein 73 in patients with primary liver cancer

BACKGROUND Microwave ablation(MWA)is an effective treatment option for patients with primary liver cancer.However,it has been reported that the MWA procedure induces a hepatic inflammatory response and injury,which may negatively affect the efficacy of MWA.As such,the discovery of reliable markers to monitor the patient’s response to MWA is needed.Golgi protein 73(GP73)has been shown to be associated with chronic liver disease.To date,the potential value of serum GP73 in the dynamic monitoring during MWA of liver cancer remains unclear.AIM To examine the effects of MWA on the serum levels of GP73 in patients with primary liver cancer.METHODS A total of 150 primary liver cancer patients with a single small lesion(≤3 cm in diameter)were retrospectively enrolled spanning the period between January 2016 and October 2018.All of the patients received MWA for the treatment of primary liver cancer.Serum GP73,alpha-fetoprotein(AFP),and widely used liver biochemical indicators[serum albumin,total bilirubin(TBIL),alanine aminotransferase(ALT),and aspartate aminotransferase(AST)]were compared before MWA and at different time points,including 1,2,and 4 wk following the ablation procedure.RESULTS Complete tumor ablation was achieved in 95.33%of the patients at 1 mo after MWA.The 1-,2-,and 3-year disease-free survival rates were 74.67%,59.33%,and 54.00%,respectively.The serum AFP levels were significantly decreased at 1,2,and 4 wk after MWA;they returned to the normal range at 12 wk after MWA;and they remained stable thereafter during follow-up in those cases without recurrence.In contrast,the serum GP73 levels were significantly increased at 1 and 2 wk after MWA.The serum GP73 levels reached the peak at 2 wk after MWA,started to decline after hepatoprotective treatment with glycyrrhizin and reduced glutathione,and returned to the pretreatment levels at 12 and 24 wk after MWA.Notably,the changes of serum GP73 in response to MWA were similar to those of TBIL,ALT,and AST.CONCLUSION Serum GP73 is markedly increased in response to MWA of liver cancer.Thus,serum GP73 holds potential as a marker to monitor MWA-induced inflammatory liver injury in need of amelioration.

Clinical evaluation of single or joint of golgi protein 73 and alpha-fetoprotein in hepatocellular carcinoma diagnosing

Objective: The aim of the present study was to further evaluate the clinical value of single or joint of golgi protein 73 (GP73) and alphafetoprotein (AFP) in diagnosis of hepatocellular (HCC). Methods: One hundred and eighteen, 94 and 47 serum samples from the patients with HCC, chronic liver disease (CLD) and liver cirrhosis (LC) were collected, respectively. Serum levels of AFP and GP73 were assayed with commercial kit according to the manufacturer's instructions. Results: Patients with HCC had higher serum concentration of AFP than that of the patients with CLD (P < 0.01), but was similar to that of the patients with LC. Serum GP73 levels in the patients with CLD or LC were significantly lower than that in the patients from HCC group (P < 0.01). Among 118 HCC patients, the positive rate of GP73 and AFP was 80.5% and 48.3%, respectively (P < 0.001). The ROC curve analysis showed that the AUC value of GP73 was higher than that of serum AFP. Moreover, the sensitivity and the accuracy of GP73 were 77.1% and 82.6%, respectively, which were greater more than that of AFP at 90% specificity (28.8% and 59.8%, respectively). The AUC, the sensitivity and the accuracy of GP73 in combination of AFP (AFP/GP73) were 0.855, 78.0% and 83.0%, respectively, which were similar to that of GP73 alone but were much higher than that of the single marker AFP. Conclusion: For HCC diagnosing, GP73 was more sensitive and specific than AFP. The diagnostic value of AFP/GP73 was similar to GP73 but was much higher than AFP.

Significance of Golgi Protein 73, Alpha-Fetoprotein and Vascular Endothelial Growth Factor Expression in Diagnosis of Primary Hepatic Cancer

Aim: We measured Golgi protein73 (GP73), alpha-fetoprotein (AFP), and vascular endothelial growth factor (VEGF) expression in primary hepatic cancer (PHC) and assessed their clinical significance. Methods: Forty-five PHC and tumor-adjacent specimens and 14 normal liver specimens were examined. GP73, AFP, and VEGF expression was measured via immunohistochemistry and a correlation of protein expression with clinical pathology of PHC was suggested. Results: GP73, AFP, and VEGF expression was significantly higher in PHC and tumor-adjacent tissue compared to tumor-adjacent tissue (0.143 ± 0.018 vs. 0.124 ± 0.027, 0.116 ± 0.026 vs. 0.098 ± 0.014, and 0.126 ± 0.027 vs. 0.092 ± 0.016, respectively;all p 0.088 ± 0.029, 0.098 ± 0.014 vs. 0.073 ± 0.011, and 0.092 ± 0.016 vs. 0.076 ± 0.018, respectively;all p < 0.05), respectively. GP73 expression was positively correlated with pathological grade and cirrhosis, but not with tumor size, nodules, clinical stage and serum AFP. VEGF expression was positively correlated with tumor size, nodules, portal vein tumor thrombus, and clinical stage, but not with the degree of tumor differentiation and serum AFP. Expression of GP73 and VEGF was greater than that of AFP in PHC (both p < 0.05). Conclusion: GP73 is highly expressed in PHC and may be a diagnostic marker. Combined detection of GP73, AFP, and VEGF is helpful for diagnosis of PHC.

Golgi protein 73, hepatocellular carcinoma and other types of cancers

Hepatocellular carcinoma(HCC)is one of the most common malignant tumors with a low survival rate.The identification of mechanisms underlying the development of HCC helps uncover cellular and mo-lecular targets for the diagnosis,prevention,and treatment of HCC.Golgi protein 73(GP73)level is up-regulated in HCC patients and potentially can be a therapeutic target.Despite many studies devoted to GP73 as a marker for HCC early diagnosis,there is little discussion about the function of GP73 in HCC tumorigenesis.Given the poor response to currently available HCC therapies,a better understanding of the role of GP73 in HCC may provide a new therapeutic target for HCC.The current paper summarizes the role of GP73 as a diagnostic marker as well as its roles in liver carcinogenesis.Its roles in other types of cancer are also discussed.

Relationship between the Level of Serum Golgi Protein 73 and the Risk of Short-term Death in Patients with ALD-ACLF

Background and Aims:As a hepatocellular carcinoma biomarker,serum Golgi protein 73(GP73)is reportedly related to inflammation.Acute-on-chronic liver failure(ACLF)is characterized by severe systemic inflammation.In this study,we aimed to explore the association between the GP73 level and short-term mortality in patients with alcohol-associated liver disease-related ACLF(ALD-ACLF).Methods:This retrospective cohort study involved 126 Chinese adults with ALD-ACLF.Baseline serum GP73 level was measured using enzymelinked immunosorbent assay.Patients were followed-up for 90 d and outcomes were assessed.Data were analyzed using multivariate Cox regression and piecewise linear regression analyses.The predictive value of GP73 and classic models for the short-term prognosis of participants were evaluated and compared using receiver operating characteristic curves.Results:The serum GP73 level was independently associated with an increased mortality risk in patients with ALD-ACLF.Compared with the lowest tertile,the highest serum GP73 level predisposed patients with ALD-ACLF to a higher mortality risk in the fully adjusted model[at 28 days:hazard ratio(HR):4.29(0.99–18.54),p=0.0511;at 90 days:HR:3.52(1.15–10.79),p=0.0276].Further analysis revealed a positive linear association.GP73 significantly improved the accuracy of the Child-Turcotte-Pugh score,model for end-stage liver disease score,and model for end-stage liver diseasesodium score in predicting short-time prognosis of patients with ALD-ACLF.Conclusions:The serum GP73 level is a significant predictor of the subsequent risk of death in patients with ALD-ACLF.GP73 improved the predictive value of classic prognostic scores.

Correlational research of Golgi phosphorylation protein 3 expression in colorectal cancer

AIM: To investigate the effect of Golgi phosphorylation protein 3(GOLPH3) expression on cell apoptosis, angiogenesis and prognosis in colorectal cancer(CRC). METHODS: The expression of GOLPH3 in CRC tissues and normal colorectal mucosae was determined by immunohistochemistry in 62 patients. In addition, immunohistochemistry was also carried out to detect the expression of vascular endothelial growth factor(VEGF), CD34 and microvessel density(MVD). Terminal deoxynucleotidyl transferase-mediated d UTP-biotin nick end labeling assay was used to determine the apoptotic index(AI). The Kaplan-Meier method was used to analyze the relationship between GOLPH3 expression and survival in another 123 CRC cases.RESULTS: Compared with normal colorectal mucosae, a notably higher level of GOLPH3 protein expression was identified in CRC tissues(53.2% vs 24.2%, P < 0.05). Positive GOLPH3 expression was significantly associated with tumor invasion depth, TNM stage, and lymph node metastasis(P = 0.001; P = 0.020; P = 0.020; P < 0.05, respectively), but not with tumor length, tumor site, and age(P = 0.363; P = 0.819; P = 0.599; P > 0.05, respectively). VEGF expression and MVD in GOLPH3-positive CRC was significantly higher than in GOLPH3-negative CRC(VEGF: 69.7% vs 31.0%; MVD: 21.45 ± 9.39 vs 14.24 ± 8.97; P < 0.05).GOLPH3 expression was negatively correlated with AI in CRC as shown by Spearman correlation analysis(r =-0.320, P < 0.05). The 5-year survival rate in GOLPH3-negative CRC(69.4%) was significantly higher than in GOLPH3-positive CRC(48.6%)(log-rank test, P < 0.05).CONCLUSION: High expression of GOLPH3 is found in CRC tissues. GOLPH3 expression may be a novel prognostic marker for CRC patients.

Evidence That Protein Disulfide Isomerase in Yeast Saccharomyces cerevisiae Is Transported from the ER to the Golgi Apparatus

Newly synthesized membrane and secretory proteins in cells undergo folding in the endoplasmic reticulum with the introduction of disulfide bonds and acquire the correct three-dimensional structure. Disulfide bonds are especially important for protein folding. It has been thought that formation of protein disulfide bonds in eukaryotes is mainly carried out by an enzyme called protein disulfide isomerase. Proteins, bearing the C-terminus of amino acids sequences with His-Asp-Glu-Leu (HDEL) sequence in yeast, in the endoplasmic reticulum (ER), which is a eukaryotic cellular organelle involved in protein synthesis, processing, and transport, have been considered to recycle between ER and Golgi apparatus. The proposal for this recycling model derives from the study of an HDEL-tagged fusion protein. Here, the localization and oligosaccharide modification of protein disulfide isomerase were investigated in yeast, and showed the first direct evidence that this intrinsic ER protein transports from ER to Golgi. Results suggest that this native protein is also accessible to post-ER enzymes, and yet accumulates in the ER.

乙型肝炎病毒感染相关肝病患者血清T淋巴细胞免疫球蛋白黏蛋白分子-3、高尔基体蛋白73变化及其临床意义的研究

目的:探讨乙型肝炎病毒(HBV)感染相关肝病患者血清T淋巴细胞免疫球蛋白黏蛋白分子-3(TIM-3)、高尔基体蛋白73(GP73)变化及其临床意义。方法:选取2020年9月至2022年10月于河南省郑州市第三人民医院诊治的100例HBV感染相关肝病患者为研究对象,其中47例慢性乙型肝炎(CHB)、35例肝硬化(LC)、18例肝细胞癌(HCC),分别纳入CHB组、LC组、HCC组,另选取本院同期体检的30例健康者纳入对照组。根据病情严重程度不同,CHB组又分为轻度CHB组(16例)、中度CHB组(19例)和重度CHB组(12例),LC组又分为代偿期LC组(15例)和失代偿期LC组(20例),HCC组又分为甲胎蛋白(AFP)阴性HCC组(8例)和AFP阳性HCC组(10例)。比较CHB组、LC组、HCC组和对照组TIM-3、GP73、丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、白蛋白和总胆红素(TBil)水平;比较CHB亚组、LC亚组和HCC亚组患者TIM-3、GP73水平;分析HBV感染相关肝病患者TIM-3和GP73与ALT、AST、白蛋白及TBil的相关性。结果:四组TIM-3、GP73、ALT、AST、白蛋白和TBil水平比较,差异有统计学意义(P<0.001);CHB组、LC组和HCC组TIM-3、GP73、ALT、AST及TBil水平均高于对照组,白蛋白水平均低于对照组(P<0.05);LC组和HCC组TIM-3、GP73、ALT、AST及TBil水平均高于CHB组,白蛋白水平均低于CHB组(P<0.05);HCC组TIM-3、GP73、ALT、AST及TBil水平均高于LC组,白蛋白水平低于LC组(P<0.05)。轻度CHB组、中度CHB组、重度CHB组TIM-3和GP73水平比较,差异有统计学意义(P<0.001);中度CHB组、重度CHB组TIM-3和GP73水平均高于轻度CHB组(P<0.05);重度CHB组TIM-3和GP73水平均高于中度CHB组(P<0.05)。失代偿期LC组TIM-3、GP73水平均高于代偿期LC组(P<0.05)。AFP阳性HCC组TIM-3、GP73水平均高于AFP阴性HCC组(P<0.05)。CHB组、LC组、HCC组患者TIM-3、GP73与ALT、AST、TBil呈正相关,与白蛋白呈负相关(P<0.05)。结论:HBV感染相关肝病患者血清TIM-3、GP73水平明显升高,CHB、LC、HCC不同疾病发展阶段其表达水平升高程度显著,且与病情发展及肝功能损伤密切相关。

慢性乙型肝炎患者HBV DNA载量及血清IL-2R、GP73、miR-21与HBVM表达模式、肝组织病理学改变的相关性

目的探讨慢性乙型肝炎患者乙型肝炎病毒(HBV)DNA载量及血清白细胞介素-2受体(IL-2R)、高尔基体蛋白73(GP73)、微小RNA-21(miR-21)与乙型肝炎病毒血清标志物(HBVM)表达模式、肝组织病理学改变的相关性。方法回顾性选取2020年1月至2022年12月四川绵阳四0四医院(绵阳市第一人民医院)收治的106例慢性乙型肝炎患者作为观察组,另纳入本院125名同期健康体检者为对照组。观察组根据肝脏炎症程度分为炎症较轻组(G_(0)~G_(2)期,n=61)和炎症较重组(G_(3)~G_(4)期,n=45);根据肝纤维化程度分为纤维化较轻组(S_(0)~S_(2)期,n=80)和纤维化较重组(S_(3)~S_(4)期,n=26);根据外周血中是否产生乙肝表面抗体(抗-HBs)分为抗-HBs阳性组(n=77)和抗-HBs阴性组(n=29)。比较观察组与对照组血清IL-2R、GP73、miR-21水平,比较不同肝脏炎症程度、不同肝脏纤维化程度、不同HBVM表达模式的慢性乙型肝炎患者HBV DNA载量、血清IL-2R、GP73、miR-21水平,并采用Spearman相关性分析分析HBV DNA载量、血清IL-2R、GP73、miR-21与肝组织病理学改变的相关性。结果观察组血清IL-2R、GP73、miR-21水平分别为(559.65±46.65)U/mL、(149.87±31.65)ng/mL、1.98±0.65,均高于对照组[(272.54±28.65)U/mL、(48.76±9.65)ng/mL、1.23±0.36],差异均有统计学意义(P<0.05)。炎症较重组HBV DNA载量、血清IL-2R、GP73、miR-21水平分别为(5.98±0.73)loads、(703.54±57.54)U/mL、(243.65±38.65)ng/mL、1.99±0.54,均高于炎症较轻组[(4.65±0.68)loads、(450.65±36.65)U/mL、(80.43±20.34)ng/mL、1.54±0.45],差异均有统计学意义(P<0.05)。纤维化较重组HBV DNA载量、血清IL-2R、GP73、miR-21水平分别为(6.03±0.98)loads、(675.65±58.04)U/mL、(189.65±41.65)ng/mL、2.34±0.34,均高于纤维化较轻组[(4.48±0.79)loads、(522.65±31.54)U/mL、(135.76±26.54)ng/mL、1.31±0.28],差异均有统计学意义(P<0.05)。抗-HBs阳性组和抗-HBs阴性组HBV DNA载量、血清IL-2R、GP73、miR-21水平比较,差异均无统计学意义(P>0.05)。HBV DNA载量、血清IL-2R、GP73、miR-21均与肝脏炎症程度呈正比(r=0.546、0.498、0.657、0.508,P<0.05),与肝脏纤维化程度呈正比(r=0.487、0.506、0.673、0.703,P<0.05)。结论慢性乙型肝炎患者血清中IL-2R、GP73、miR-21表达较高,且患者HBV DNA载量、血清IL-2R、GP73、miR-21水平与肝脏炎症及纤维化程度呈正比,但其与HBVM表达模式无明显相关性。

乳腺癌患者血清GP73、miR-27a水平的变化及其与临床病理、化疗疗效的相关性

目的 分析乳腺癌患者血清高尔基体蛋白73 (GP73)、微小RNA-27a (miR-27a)水平变化及其与临床病理特征、化疗疗效的相关性。方法 选取2021年10月至2023年1月南阳市中心医院收治的80例乳腺癌患者作为研究组,另选取同期健康女性志愿者80例作为对照组。比较两组受检者以及研究组不同临床病理特征患者的血清GP73、miR-27a水平,并比较研究组不同化疗疗效患者化疗前后的血清GP73、miR-27a水平及变化值(△GP73、△miR-27a),采用Spearman相关法分析化疗前血清GP73、miR-27a水平与临床病理特征相关性,以及△GP73、△miR-27a与化疗疗效的相关性。结果 研究组患者的血清GP73、miR-27a水平分别为(121.35±40.12) ng/L、0.71±0.20,明显高于对照组的(47.68±15.29) ng/L、0.21±0.07,差异均有统计学意义(P<0.05);研究组患者中,不同临床分期、分化程度、肿瘤直径、淋巴结转移患者血清GP73、miR-27a水平比较差异均有统计学意义(P<0.05);经Spearman相关法分析结果显示,研究组血清GP73、miR-27a水平与乳腺癌临床分期、肿瘤直径、淋巴结转移呈正相关(P<0.05),与分化程度呈负相关(P<0.05);无效者化疗前后的血清GP73、miR-27a水平明显高于有效者,差异均有统计学意义(P<0.05);无效者△GP73、△miR-27a分别为13.52±3.16、0.07±0.02,明显低于有效者的21.31±5.42、0.12±0.03,差异均有统计学意义(P<0.05);经Spearman相关法分析结果显示,△GP73、△miR-27a与化疗疗效呈正相关(r=0.658、0.714,P<0.05)。结论 血清GP73、miR-27a水平与乳腺癌临床病理特征、化疗疗效密切相关,可以作为评估病情进展及化疗疗效的潜在指标。

乙型肝炎相关性肝癌患者T淋巴细胞、白介素-28B及高尔基体蛋白73的表达及临床意义

目的:分析乙型肝炎相关性肝癌患者T淋巴细胞、白介素-28B (IL-28B)及高尔基体蛋白73 (GP73)的表达及临床意义。方法:选取2018年10月—2021年10月商丘市第一人民医院收治的119例乙型肝炎相关性肝癌患者作为观察组,选取同期体检的112例健康人群作为对照组。比较两组研究对象血清IL-28B、GP73及T淋巴细胞水平,分析IL-28B、GP73、T淋巴细胞与病理特征及预后的关系。结果:观察组血清IL-28B、GP73及CD8^(+)表达水平均高于对照组,CD3^(+)、CD4^(+)及CD4^(+)/CD8^(+)均低于对照组,差异有统计学意义(t=148.380、13.155、9.827、9.939、16.367、11.453,P<0.05)。不同年龄、性别、肿瘤直径的乙型肝炎病毒(HBV)相关性肝癌患者血清中IL-28B、GP73水平比较,差异无统计学意义(P>0.05)。有淋巴结转移、TNM分期Ⅲ~Ⅳ期、低分化、有血管浸润者血清中IL-28B、GP73水平高于无淋巴结转移、TNM分期Ⅰ~Ⅱ期、中/高分化、无血管浸润者,差异有统计学意义(P<0.05)。HBV相关性肝癌患者血清中CD3^(+)、CD4^(+)、CD8^(+)在不同年龄、性别、肿瘤直径中比较,差异无统计学意义(P>0.05),CD3^(+)、CD4^(+)、CD8^(+)水平在不同淋巴结转移情况、TNM分期、分化程度及血管浸润中比较,差异无统计学意义(P>0.05)。死亡者血清GP73、IL-28B水平均高于生存者,CD4^(+)/CD8^(+)指标低于生存者,差异有统计学意义(t=16.629、2.082、9.267,P<0.05)。结论:乙型肝炎相关性肝癌患者血清IL-28B、GP73及CD8^(+)表达水平明显升高,CD3^(+)、CD4^(+)及CD4^(+)/CD8^(+)指标下降,IL-28B、GP73及CD4^(+)/CD8^(+)水平与相关病理特征、预后具有密切的联系。

GM130通过14-3-3ζ对卵巢癌细胞增殖的影响及机制研究

目的探讨高尔基体基质蛋白130(GM130)通过14-3-3ζ对卵巢癌细胞增殖的影响及可能机制。方法采用免疫组化法检测在20例正常卵巢上皮组织和42例卵巢上皮恶性肿瘤中GM130和14-3-3ζ的表达,分析二者相关性。采用Western blot和RT-PCR法检测卵巢癌SKOV3/A2780细胞株GM130和14-3-3ζ蛋白及其mRNA表达情况,筛选出高表达细胞株。采用免疫荧光染色法检测GM130与14-3-3ζ在卵巢癌细胞中的共表达情况。将设计好的重组表达质粒shRNA-GM130片段稳转进入卵巢癌细胞中,采用Western blot和RT-PCR筛选出降低GM130的最佳片段。细胞分为三组:空白组(WT)、对照组(NC)、低表达组(313),采用CCK法和流式细胞术分别检测各组卵巢癌细胞生殖情况及周期变化情况,采用Western blot法检测各组14-3-3ζ、GRASP65、P115及增殖相关蛋白表达水平。结果GM130和14-3-3ζ在卵巢恶性肿瘤组织中的表达水平高于正常卵巢组织(P<0.001)。在卵巢恶性肿瘤组织中,GM130和14-3-3ζ呈正相关关系(r=0.873,P<0.001)。GM130蛋白及其mRNA在SKOV3细胞中的表达量高于A2780细胞(P<0.05),14-3-3ζ蛋白及其mRNA在SKOV3细胞和A2780细胞中比较差异无统计学意义(P>0.05)。后续实验选用SKOV3细胞。免疫荧光共定位染色显示,GM130与14-3-3ζ主要在胞质表达,前者近核膜部分呈堆叠样表达量较高,后者胞核中表达较少,二者可能存在共定位关系。转染313组片段后,对GM130的抑制效果最好。转染质粒313组细胞增殖能力降低,细胞在G1期阻滞的数量增多,G2期阻滞数量减少,S期阻滞的细胞数量稍减少,GM130、14-3-3ζ、P115、Cyclin A、Cdc25A蛋白相对表达水平降低,P21蛋白相对表达水平升高(P<0.05)。结论抑制GM130可抑制卵巢癌细胞增殖,其机制可能与抑制14-3-3ζ表达,影响卵巢癌细胞周期有关。

血清GP73与慢性乙型病毒性肝炎患者肝功能及肝纤维化指标的相关性

目的分析血清高尔基体蛋白73(GP73)与慢性乙型病毒性肝炎(CHB)患者肝功能及肝纤维化指标的相关性。方法选取延安大学附属医院2023年1月至6月收治的93例CHB患者作为研究对象,按照病情严重程度将其分为轻度组(41例)、中度组(32例)及重度组(20例)。检测所有研究对象的血清学指标、肝功能指标、肝纤维化指标;采用Pearson相关性分析CHB患者血清GP73、可溶性生长刺激表达基因2蛋白(s ST2)、趋化因子配体13(CXCL13)、白细胞介素-18(IL-18)与肝功能、肝纤维化指标的相关性。结果轻度组、中度组、重度组的血清GP73、s ST2、CXCL-13、IL-18水平均呈逐渐升高趋势,差异具有统计学意义(P<0.05)。轻度组、中度组、重度组的丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)及γ-谷氨酰转移酶(GGT)水平均呈逐渐升高趋势,差异具有统计学意义(P<0.05)。轻度组、中度组、重度组的层粘连蛋白(LN)、透明质酸(HA)、Ⅲ型前胶原(PC-Ⅲ)及Ⅳ型胶原(Ⅳ-C)水平均呈逐渐升高趋势,差异具有统计学意义(P<0.05)。Pearson相关性分析显示,CHB患者血清GP73、s ST2、CXCL-13、IL-18水平与肝功能、肝纤维化指标水平均呈正相关(P<0.05)。结论CHB患者血清GP73、s ST2、CXCL-13、IL-18水平升高会导致肝功能受损程度加剧,促进肝纤维化,有望成为CHB诊断以及病情严重程度评估的可靠生物学标志物。

血清AFP、AFP-L3、GP73及DCP在慢性乙肝和肝癌诊治中的价值分析

目的探讨血清甲胎蛋白(AFP)、甲胎蛋白异质体(AFP-L3)、高尔基体73(GP73)及异常凝血酶原(DCP)在慢性乙肝及肝癌诊治中的临床价值。方法回顾性选取2022年1月至2023年3月在浙江大学医学院附属金华医院就诊的肝癌患者78例(肝癌组)、慢性乙肝患者90例(慢性乙肝组)为研究对象,另择同期在本院健康体检者70名作为正常对照组。采集研究对象清晨空腹静脉血检测血清AFP、AFP-L3、GP73及DCP。比较3组研究对象血清AFP、AFP-L3、GP73及DCP阳性率和水平;分析以上指标血清水平对肝癌的诊断效能;比较肝癌组患者手术前后以上指标的血清水平。结果3组研究对象血清AFP、AFP-L3、GP73及DCP阳性率与水平比较差异均有统计学意义(均P<0.05),且血清GP73、DCP水平肝癌组>慢性乙肝组>正常对照组(均P<0.05)。AFP、AFP-L3、GP73与DCP诊断肝癌的AUC分别为0.745、0.916、0.753和0.785。其中AFPL3的AUC最大,最佳截断值为9.35%,灵敏度为0.859,诊断效能较高;AFP的最佳截断值为9.37 ng/mL,特异度最高为0.900,但其灵敏度较低为0.564。肝癌组患者手术后血清AFP、AFP-L3、GP73及DCP水平均较手术前降低(均P<0.05)。结论血清AFP、AFP-L3、GP73及DCP对慢性乙肝及肝癌有一定的辅助诊断价值,可能是肝癌患者术后预后的潜在预测指标。

甲状腺激素受体相互作用物11基因变异所致软骨生成不全IA型家系遗传学分析

软骨生成不全IA型是一种罕见的致死性疾病,以常染色体隐性方式遗传,该疾病的发生与人14号染色体上甲状腺激素受体相互作用物11(TRIP11)基因变异有关。本研究采集了1例超声检查疑似致命性骨骼发育不良胎儿的流产皮肤组织及其父母的静脉血,通过提取基因组DNA,应用全外显子组测序技术对胎儿组织及其父母进行平行测序,对疑似致病变异用Sanger测序进行验证;并对以往报道基因检测结果进行文献复习,结合文献复习探讨该病的临床特点。结果发现了胎儿TRIP11检测到复合杂合变异c.790C>T(p.R264*)/c.589-2A>G,两位点分别来自父亲和母亲,符合常染色体隐性遗传。本研究报道的TRIP11基因复合杂合变异尚未见报道,拓宽了软骨生成不全1A型的基因变异谱,为该家庭的遗传咨询及产前诊断提供了重要的分子基础。

胃癌患者血清中高尔基体蛋白73、claudin-1的表达水平及其临床意义

目的探讨胃癌患者血清中高尔基体蛋白73、claudin-1表达水平及其临床意义。方法采用酶联免疫吸附法(ELISA)检测76例胃癌患者(胃癌组)和30例健康体检者(对照组)血清中的GP73、claudin-1水平,比较2组的血清GP73、claudin-1水平差异并经受试者工作特征(ROC)曲线评估血清GP73、claudin-1水平鉴别诊断胃癌的临床效能,分析血清GP73、claudin-1水平与胃癌临床病理特征和总生存期(overall survival,OS)、无进展生存期(progression-free survival,PFS)的关系。结果胃癌组血清GP73、claudin-1水平低于对照组,差异均具有统计学意义(P<0.05)。ROC曲线分析显示,对胃癌的诊断,GP73最佳截断值21.18μg/L,敏感度83.20%、特异度85.73%;claudin-1最佳截断值0.72 ng/ml,敏感度82.16%、特异度84.44%。依据血清GP73、claudin-1水平截断值分别分成高、低表达组,GP73高表达组、claudin-1高表达组与GP73低表达组、claudin-1低表达组在浸润深度、分化程度、肿瘤大小、组织学类型、TNM分期方面比较,差异均具有统计学意义(P<0.05)。生存分析显示,GP73低表达组总生存率(28.21%)低于GP73高表达组总生存率(59.46%)(P<0.05),GP73低表达组无进展生存率(20.51%)低于GP73高表达组无进展生存率(40.54%)(P<0.05);claudin-1低表达组总生存率(31.58%)低于claudin-1高表达组总生存率(57.89%)(P<0.05),claudin-1低表达组无进展生存率(21.05%)低于claudin-1高表达组无进展生存率(36.84%)(P<0.05)。结论胃癌患者血清GP73水平、claudin-1水平均明显下降,且均与恶性病理特征和不良预后有关,可作为潜在的鉴别诊断胃癌的血清肿瘤学指标。

血清HMGB1、GP73、IL-37与HBV-ACLF患者HBV-DNA载量的关系及对预后的预测价值

目的探究乙型肝炎病毒相关慢加急性肝衰竭(HBV-ACLF)患者血清高迁移率族蛋白B1(HMGB1)、高尔基体蛋白73(GP73)、白细胞介素-37(IL-37)与HBV-DNA载量的关系及对预后的预测价值。方法选取2018年7月至2023年7月中国人民解放军联勤保障部队第九八〇医院收治的112例HBV-ACLF患者的临床资料进行回顾性分析,根据HBV-CALF患者入院90 d内临床结局分为死亡组(42例)与生存组(70例)。比较两组临床资料及血清HMGB1、GP73、IL-37水平,分析HBV-CALF患者预后的影响因素,分析血清HMGB1、GP73、IL-37与HBV-DNA载量的关系,评价血清HMGB1、GP73、IL-37对HBV-CALF患者预后的预测价值。结果死亡组在病情分期、腹膜炎、肝性脑病、肺部感染、HBV-DNA载量、终末期肝病评分模型(MELD)评分方面与生存组比较,差异有统计学意义(P<0.05);死亡组血清HMGB1、GP73、IL-37水平均较生存组高(P<0.05)。病情分期、腹膜炎、肝性脑病、肺部感染、HBV-DNA载量、MELD评分及血清HMGB1、GP73、IL-37水平均为HBV-ACLF患者预后的独立影响因素(P<0.05)。HBV-ACLF患者血清HMGB1、GP73、IL-37水平均与HBV-DNA载量呈负相关(P<0.05)。血清HMGB1、GP73、IL-37预测HBV-ACLF患者预后的曲线下面积(AUC)分别为0.781、0.790、0.782,三者联合预测的AUC最大,为0.944,灵敏度、特异度分别为86.33%、91.43%。结论血清HMGB1、GP73、IL-37水平与HBV-CALF患者HBV-DNA载量及预后密切相关,3项指标联合检测有助于提高对预后的预测效能。

血清FIB-4、CHI3L1、GP73、AFP联合检测在乙型肝炎肝硬化鉴别诊断中的价值

目的:研究血清纤维化-4(FIB-4)、壳多糖酶3样蛋白1(CHI3L1)、高尔基体蛋白73(GP73)、甲胎蛋白(AFP)联合检测在乙型肝炎肝硬化鉴别诊断中的价值。方法:选取2020年1月—2023年2月于赣州市赣县区人民医院就诊的乙型肝炎患者80例,按照是否发生肝硬化将其进行分组,其中发生肝硬化患者纳入硬化组(n=38),未发生肝硬化患者纳入对照组(n=42),比较两组肝功能生化指标[谷丙转氨酶(ALT)、谷草转氨酶(AST)、总胆红素(TBIL)、白蛋白(ALB)],比较两组血清FIB-4、CHI3L1、GP73、AFP水平,并采用ROC曲线分析上述指标的诊断价值。结果:两组ALT、AST、TBIL、ALB水平差异均无统计学意义(P>0.05),硬化组血清FIB-4、CHI3L1、GP73、AFP水平均显著高于对照组,差异均有统计学意义(P<0.05)。由ROC曲线得知,FIB-4的AUC可达0.956,敏感度可达100%,特异度可达90.48%,截断值为3.32;CHI3L1的AUC可达0.956,敏感度可达94.74%,特异度可达92.86%,截断值为158.15 ng/mL;GP73的AUC可达0.904,敏感度可达94.74%,特异度可达76.19%,截断值为125.14 ng/mL;AFP的AUC可达0.734,敏感度可达60.53%,特异度可达85.71%,截断值为30.50μg/L;联合诊断的AUC可达0.977,敏感度可达100%,特异度可达92.86%。结论:乙型肝炎肝硬化患者可采用FIB-4、CHI3L1、GP73、AFP进行联合诊断,使患者可及时确诊并进行治疗。

基于GALAD模型分析肝脏硬度测量值和高尔基体糖蛋白-73在丙型肝炎病毒相关肝细胞癌患者中的诊断价值

目的基于GALAD模型分析高尔基体糖蛋白-73(Golgi protein 73,GP73)和肝脏硬度测量值(liver stiffness measurement,LSM)在丙型肝炎病毒(hepatitis C virus,HCV)相关肝细胞癌(hepatocellular carcinoma,HCC)患者中表达及诊断价值。方法选取2019年1月至2022年1月西安交通大学第一附属医院榆林医院收治的75例慢性HCV感染并确诊HCC患者(HCC组)和85例HCV感染非HCC患者(对照组)作为研究对象。采用全自动生化仪检测两组患者肝功能生化指标;采用全自动化学发光免疫分析仪分析两组患者甲胎蛋白(α-fetoprotein,AFP)、甲胎蛋白异构体L3(α-fetoprotein-L3,AFP-L3)、异常凝血酶原(des-γ-carboxy prothrombin,DCP)及GP73水平,并根据公式计算GALAD模型得分;采用肝纤维化无创扫描仪测量LSM;采用受试者工作特征曲线分析HCC诊断价值;采用Pearson相关方法进行相关性分析。结果HCC组患者肝功能指标、AFP、DCP、AFP-L3、LSM、GP73水平及GALAD模型评分均显著高于对照组(均P<0.05);HCC组患者不同肿瘤分期亚组AFP、DCP、AFP-L3、LSM、GP73水平及GALAD模型评分比较差异均有统计学意义(均P<0.05),且分期越晚指标水平和GALAD模型评分越高,各分期亚组间差异均有统计学意义(均P<0.05)。相关性分析显示,LSM、GP73水平与GALAD模型评分均呈线性正相关(r=0.622,P<0.001;r=0.532,P<0.001)。LSM、GP73及GALAD三项联合诊断HCC的曲线下面积为0.933,检测敏感度为94.56%,特异度为83.23%,均显著高于单独诊断(均P<0.05)。结论GALAD模型在HCV相关HCC诊断中显示了良好的效能,LSM、GP73作为HCC诊断标志物与GALAD模型评分呈正相关,且联合GALAD模型对HCC表现出更好的诊断效能。