The urokinase-type plasminogen activator and inhibitors in resectable lung adenocarcinoma

BackgroundThe urokinase-type plasminogen activator (uPA) system is closely related to the occurrence and progression of cancer in many aspects. Previous studies demonstrated that the conclusions about the prognosis value of uPA, plasminogen activator inhibitor 1 (PAI-1) and plasminogen activator inhibitor 2 (PAI-2) in lung cancer are controversial, so this study was performed for the exploration of the predictive effect of uPA, PAI-1 and PAI-2 on the overall survival (OS) of resectable pulmonary adenocarcinoma patients.MethodsUPA, PAI-1 and PAI-2 expression levels were assayed by immunohistochemical staining based on tissue microarray (TMA) that is composed of formalin-fixed paraffin-embedded specimens from 84 resectable lung adenocarcinoma patients from July 2004 to June 2009. The relationship of IHC, mRNA expression levels of three molecules were investigated respectively. The three molecules’ relationship with clinicopathologic parameters and OS was explored by Chi-square, Kaplan-Meier, and Cox regression analyses. The Cancer Genome Atlas (TCGA) database was used to analyze differential gene expressions of RNA-sequencing data of pulmonary adenocarcinoma and normal tissues, and Kaplan-Meier methods were adopted to confirm the prognostic value of uPA, PAI-1 and PAI-2 in resectable lung adenocarcinoma in TCGA database and the R package MethylMix was used to conduct an analysis integrating methylation data and gene expression of RNA-sequencing data based on TCGA.ResultsUPA, PAI-1 and PAI-2 had much higher IHC expression levels in tumor than those in the normal tissues (uPA, Z = -10.511; PAI-1, Z = -4.836; PAI-2, Z = -6.794; all P < 0.0001). High DNA methylation level of gene uPA resulted in the decrease of its expression. In addition, expression level of PAI-2 was positively associated with tumor size (χ² = 8.372, P = 0.004). Multivariate analyses showed TNM stage III was an independent adverse prognostic factor (hazard ratio = 3.736, 95 % confidence interval = 1.097–12.72, P = 0.035). Kaplan-Meier method revealed that uPA, PAI-1 and PAI-2 expression levels were not related to the OS for 84 resectable lung adenocarcinoma patients. According to TCGA data, PAI-1 expression level was identified as a potential adverse predictor for prognosis of resectable lung adenocarcinoma (Gehan-Breslow-Wilcoxon test, P = 0.025).ConclusionsOur data show that, the expression levels of uPA, PAI-1 and PAI-2 are significantly up-regulated in resectable lung adenocarcinoma. Besides, this study highlights PAI-1 as a latent adverse prognostic factor in resectable adenocarcinoma of lung.     

Prognostic impact of lncRNA-ATB expression in malignant solid tumors: A meta-analysis

PurposeNumerous studies have reported the prognostic role of lncRNA-ATB high expression in solid tumours, but its prognostic effect is still uncertain. Therefore, the purpose of this meta-analysis was to further comprehensively verify the prognostic role of the lncRNA-ATB high expression in solid tumours.MethodsA literature search was performed using the electronic platforms to obtain relevant research studies published up to 31 May 2019. Confidence intervals of research endpoints in each study were extracted and merged. All data analysis was performed using Stata12.0 software.ResultsA total of 2120 patients with solid cancers in 14 studies were enrolled in our meta-analysis eventually. The analysis results revealed that high expression of lncRNA-ATB was related to lower OS (HR:1.46, P < 0.001), shorter DFS(HR:1.73, P < 0.001), and earlier RFS (HR:2.67, P < 0.001). Besides, the high expression of lncRNA-ATB has a considerable risk of lymph node metastasis (OR:2.13, P = 0.017)and perineural invasion (OR:1.58, P = 0.018).ConclusionsMeta-analysis showed that the high lncRNA-ATB expression was a poor prognostic marker in multiple cancer types. The high expression of lncRNA-ATB symbolizes the high risk of lymph node metastasis and perineural invasion in cancer patients.     

乳腺癌中高迁移率族蛋白B1和表皮生长因子受体1的表达及相关性研究

目的 探讨乳腺癌组织中高迁移率族蛋白B1(HMGB1)和表皮生长因子受体1(EGFR)的表达情况、相关性,及其对患者预后的影响。方法 纳入2007年1月-2018年12月东阳市人民医院病理科浸润性乳腺癌石蜡标本392例。患者均为女性;年龄26～90岁,中位年龄52岁。采用免疫组织化学EnVision法,检测标本中HMGB1蛋白在细胞核、细胞质的表达情况以及EGFR蛋白在细胞膜的表达情况,分析HMGB1蛋白与EGFR蛋白表达的相关性。根据HMGB1蛋白在细胞核及细胞质表达状态分为细胞核低表达且细胞质阴性组、细胞核高表达且细胞质阴性组、细胞核低表达且细胞质阳性组、细胞核高表达且细胞质阳性组,比较4组间EGFR蛋白的表达情况。分别观察细胞核HMGB1蛋白高表达+EGFR蛋白阳性、细胞质HMGB1蛋白阳性+EGFR蛋白阳性时对患者预后的影响。结果 (1)乳腺癌中,HMGB1蛋白在细胞核和细胞质阳性表达率分别为80.1%(314/392)和15.1%(59/392),EGFR蛋白在细胞膜阳性表达率为53.6%(210/392)。(2)细胞核HMGB1蛋白高表达患者的EGFR蛋白阳性率56.1%(176/314),高于细胞核HMGB1蛋白低表达的EGFR蛋白阳性率43.6%(34/78),差异有统计学意义(χ²=3.901, P<0.05);Spearman相关分析显示细胞核HMGB1蛋白高表达和EGFR蛋白阳性呈正相关(r=0.100, P<0.05)。细胞质HMGB1蛋白阳性患者的EGFR蛋白阳性率(66.1%,39/59),高于细胞质HMGB1蛋白阴性的EGFR蛋白阳性率(51.4%,171/333),差异有统计学意义(χ²=4.384, P<0.05);Spearman相关分析显示细胞质HMGB1蛋白阳性和EGFR蛋白阳性表达亦呈正相关(r=0.106, P<0.05)。(3)HMGB1蛋白细胞核低表达且细胞质阴性68例、细胞核高表达且细胞质阴性265例、细胞核低表达且细胞质阳性10例、细胞核高表达且细胞质阳性49例,4组中EGFR蛋白阳性率分别为42.6%(29/68)、53.6%(142/265)、50.0%(5/10)、69.4%(34/49),组间比较差异有统计学意义(χ²=8.242, P<0.05)。(4)392例乳腺癌病例中,235例获得了预后生存分析资料。患者术后随访时间为3～80个月,平均60个月。生存分析显示,在235例患者中,5年累积生存率为90.6%,5年无复发累积生存率为81.3%。细胞核HMGB1蛋白高表达且EGFR阳性的患者5年无复发累积生存率为75.2%,低于其他患者的85.8%,差异有统计学意义(χ²=4.171、P<0.05)。细胞核HMGB1蛋白高表达+EGFR阳性的患者5年累积生存率为89.1%,与其他患者的91.8%比较,差异无统计学意义(χ²=0.557、P＞0.05)。细胞质HMGB1蛋白阳性+EGFR阳性的患者5年无复发累积生存率为72.2%,5年累积生存率为83.3%,分别低于其他患者的82.0%、91.2%,但差异均无统计学意义(χ²=1.070、1.307,P值均＞0.05)。结论 细胞核及细胞质HMGB1蛋白的表达均与EGFR蛋白表达正相关,并且细胞核或细胞质HMGB1蛋白与EGFR蛋白同时高表达的患者有更低的5年无复发累积生存率和5年累积生存率。同时抑制HMGB1和EGFR可能成为抗乳腺癌治疗的新策略。     

Soluble urokinase plasminogen activator receptor (suPAR) is lower in disease-free patients but cannot rule out incident disease in patients with suspected cancer

BackgroundAccurate first-line diagnostics are essential for early recognition of cancer but also to identify patients free of disease. The biomarker soluble urokinase plasminogen activator receptor (suPAR) is elevated in patients with cancer or non-malignant disease compared to disease-free patients. We tested if low suPAR could be used to identify disease-free patients in an accelerated cancer diagnostics program, including ruling out cancer.MethodsPatients with serious nonspecific symptoms and signs of cancer (NSSC) were included at the Diagnostic Outpatient Clinic, Copenhagen University Hospital Hvidovre, Denmark. Data from a clinical examination, including blood tests and imaging, was combined with national registry data on diagnoses and mortality. The association between blood suPAR and the primary outcome of disease-free (i.e., absence of incident disease and mortality) within 1-year follow-up was analysed with logistic regression analysis.ResultsOf 1583 patients included, 349 (22.0%) were diagnosed with cancer, 837 (52.9%) with non-malignant disease, and 392 (25.8%) were disease-free within one year. Admission suPAR was significantly lower in disease-free patients compared to patients with cancer or non-malignant disease (P < 0.001), area under the curve 0.67 (95% confidence interval (CI): 0.64–0.70). The highest positive predictive value (PPV) for the outcome of disease-free was 0.55 (95% CI: 0.41–0.68) at a suPAR of 1.65 ng/mL. Patients who died had significantly higher suPAR compared to patients who survived in all disease subgroups. The AUC of suPAR for 1-year mortality was 0.80 (95% CI: 0.77–0.83).ConclusionssuPAR was significantly lower in disease-free individuals compared to patients with cancer or other conditions, but the PPV was not sufficiently high to terminate further clinical investigation with appropriate safety. Elevated suPAR may be a useful prognostic marker for adverse outcomes.     

The expression levels and prognostic value of high temperature required A2 (HtrA2) in NSCLC

High temperature required A2 (HtrA2) is a serine kinase that is released from mitochondria into the cytosol upon apoptotic stimuli, inducing apoptosis in various cancers. Thus, analysis of the expression of HtrA2 in non-small-cell lung cancer (NSCLC) tissues is needed for the understanding of this malignancy. In this study we firstly analyzed the apoptosis effect of HtrA2 in A549 cells by RNA interference and cisplatin with Western blot and flow cytometry. Then HtrA2 expression was evaluated by Western blot and immunohistochemistry in NSCLC tissues. Western blot and flow cytometry analyses indicated that deletion of HtrA2 was negatively correlated with apoptosis-induced protein in A549 cells. HtrA2 was lowly expressed in NSCLC and significantly associated with histological differentiation and clinical stage. Besides, low expression of HtrA2 was a prognostic factor for NSCLC patients’ inferior survival. In conclusion, HtrA2 might promote the apoptosis of NSCLC cells, and serve as a target for NSCLC's treatment.     

我国北方地区急性、亚急性肝衰竭病因与预后分析

目的 探讨我国北方地区急性、亚急性肝衰竭患者的病因特点及其与预后关系.方法 回顾性分析我院2002年1月至2013年12月收治的655例急性、亚急性肝衰竭患者的病因及转归的相关临床资料.结果 655例急性、亚急性肝衰竭病因构成：病毒感染仍是首要原因,占比38.17％,其次为病因不明36.95％及药物引起（22.75％）.病因变迁：2002年至2005年,病毒感染是急性、亚急性肝衰竭首要病因,占比58.2％～50％,尤其是嗜肝病毒感染（HAV＋ HBV＋ HEV） 53.5％～44.4％.从2006年嗜肝病毒感染明显下降,而不明原因及药物所致呈逐步上升趋势,在2009年不明原因取代病毒感染成为最主要病因.患者总体改善率为34.81％,其中HEV感染所致的预后好于不明原因（P＜0.05）.结论我国北方地区急性、亚急性肝衰竭病因构成发生改变,不明原因所致逐渐增多并取代病毒感染成为最主要病因,不同病因预后不同.     

高尔基体蛋白73在原发性肝癌预后判断中的应用价值

目的 探讨血清高尔基体蛋白73（GP73）在原发性肝癌预后判断中的价值.方法 酶联免疫吸附试验定量检测血清GP73,分别测定63例原发性肝癌患者术前、术后（2周、4周）以及术后3～12个月复发的21例重新入院患者的GP73的浓度.结果 原发性肝癌患者术前GP73平均水平为（240.5±81.4） ng/ml,手术治疗后2周GP73平均浓度为（114.4±34.1）ng/ml,治疗后4周平均浓度为（57.6±23.3） ng/ml,治疗前浓度显著高于治疗后浓度（P＜0.05）.肝癌复发的患者重入院后GP73浓度[（181.2±72.4） ng/ml]明显高于GP73术后的浓度（P＜0.05）.结论 GP73作为一个新型肝癌血清标记物在判断肝癌预后中具有较好的应用价值.     

90例舌癌术后患者18F-FDG符合线路显像研究及预后分析

目的 探讨舌癌术后患者的18F-FDG符合线路显像结果并分析舌癌预后的危险因素.方法 90例行手术切除并经病理诊断为舌癌的患者均在手术治疗≥3月之后行18F-FDG符合线路显像,计算符合线路显像对舌癌术后复发和（或）转移的诊断效能.舌癌预后分析中,采用Kaplan-Meier法计算生存率,Logrank检验法进行单因素预后分析,Cox回归模型及逐步回归向后最大似然法进行多因素预后分析.结果 18F-FDG符合线路显像对舌癌术后复发和（或）转移的诊断灵敏度、特异度、准确度、阳性预测值和阴性预测值分别为95.1％ （58/61）、69.0％（20/29）、86.7％（78/90）、86.6％（58/67）、87.0％（20/23）.在34例舌癌术后复发患者中,复发部位以舌体（32.4％,11/34）最为多见.在40例舌癌术后转移患者中,主要为淋巴结转移（65.1％,41/63）,其次为肺转移（27.0％,17/63）、骨骼（6.3％,4/63）转移.90例舌癌术后患者的总体1年生存率为82.5％,3年生存率为54.7％,5年生存率为52.9％.单因素预后分析显示,舌癌术后生存率与TNM临床分期、病理分化等级、早期淋巴结转移、局部复发及远处转移相关（χ2=26.282、9.629、9.629、9.442和4.928,P均＜0.05）.多因素预后分析显示,舌癌术后的预后危险因素为TNM临床分期、病理分化等级、早期淋巴结转移、局部复发、延迟淋巴结转移及远处转移（Wald值=9.855、6.585、5.042、6.271、4.354和5.134,P均＜0.05）.结论 18F-FDG符合线路显像在舌癌术后监测及预后评估中为一种有效的无创性检查方法.     

脑白质病变的研究进展

脑白质病变与临床上许多疾病密切相关,而且影响到了有关疾病的预后。本文就近年来脑白质病变的研究进展进行了综述,希望能为今后的研究提供新的思路。     

West syndrome associated with Down syndrome: Case report and literature review

West syndrome is the most frequent cause of epilepsy in Down syndrome. West syndrome is often associated with poor long-term prognosis in most of children. We report a girl with West syndrome associated with Down syndrome which occurred at 8 months of age for repetitive flexor spasms and electroencephalography (EEG) showed hypsarrhythmia. She had Down syndrome facies, microcephaly, psychomotor development delay and axial hypotonia. Computed tomography of the brain was normal. Her karyotype was 47, XX, +21. Phenobarbital therapy was immediately effective with good clinical control of seizures, while the EEG monitored after one month was unchanged. At 2 years of age, the patient had hypertonic status epilepticus following a lung infection. The EEG showed a persistence of hypsarrhythmia. Sodium valproate and hydrocortisone therapy was effective with good seizure control but her psychomotor development was severely impaired. After a follow-up of 7 years, the patient presents growth retardation, microcephaly, severe psychomotor development delay, generalized hypotonia and tetraparesis. Knowledge of West syndrome in Down syndrome allows the early detection and prompt management of this neurological complication in order to optimize psychomotor development and improve the quality of life of these children.