1.Effect of the expression level of diacylglycerol kinase gamma in paracancerous tissue on postoperative survival in patients with hepatocellular carcinoma
Xiangjun1,2a QIAN ; Zhengyang3 GUO ; Li1 WANG ; Hanxiao1 NIE ; Tao1 HE ; Xiaoqian1 WANG ; Baishun1 WAN ; Mingjie2b YAO ; Ling1 ZHANG
Journal of Clinical Hepatology 2021;37(5):1091-1096.
ObjectiveTo investigate the effect of the expression level of diacylglycerol kinase gamma (DGKγ) in paracancerous tissue on the postoperative prognosis of patients with hepatocellular carcinoma (HCC) and its clinical value. MethodsRelated clinical data were collected from 78 HCC patients who were admitted and underwent surgical resection from December 2008 to August 2012 in the Affiliated Cancer Hospital of Zhengzhou University. Quantitative real-time PCR was used to measure the mRNA expression level of DGKγ in paracancerous tissue, and then the 78 patients were divided into low expression group (DGKγ <0.086 2, LEP group) and high expression group (DGKγ ≥0.086 2, HEP group). Basic data and clinical features were compared between the two groups. The t-test and the Mann-Whitney U test were used for comparison of continuous data, and the chi-square test and the corrected chi-square test were used for comparison of categorical data. Univariate and multivariate Cox regression analyses were used to investigate independent influencing factors for survival and prognosis, and the Kaplan-Meier method was used to analyze the overall survival trends of all patients and the LEP and HEP groups in each subgroup of Barcelona Clinic Liver Cancer (BCLC) stages. ResultsThe multivariate Cox regression analysis showed that the expression level of DGKγ (HR=1.913,95%CI: 1.111-3.296,P=0.019), HBsAg (HR=2.645,95%CI:1.264-5.537,P=0.010), Alb (HR=0.952,95%CI:0.916-0.990,P=0.013), BCLC stage (HR=1.702,95%CI:1267-2.286,P<0001) and tumor size (HR=1.083,95%CI:1.019-1.152,P=0011) were independent influencing factors for long-term survival of HCC patients; the LEP group had a significantly longer median survival time than the HEP group (45.0 months vs 22.9 months, P=0002 5). The stratified analysis showed that for BCLC stage A HCC, the LEP group had significantly better long-term survival than the HEP group (P=0.034 5); for BCLC stage B/C HCC, the LEP group had a longer median survival time than the HEP group (16.5 months vs 10.8 months), but there was no significant difference in short- and long-term survival between the two groups (P>0.05). ConclusionThe expression level of DGKγ in paracancerous tissue may be a new index for predicting and evaluating the long-term survival risk of HCC patients after surgery and has certain value in clinical application.
2.Influencing factors for the clinical effect of emergency endoscopic therapy in treatment of acute-on-chronic liver failure with gastroesophageal variceal bleeding
Li1 LI ; Pengpeng1 DING ; Jianhong1 CHEN ; Yadan1 WANG ; Chunmei1 GUO ; Mingming1 MENG ; Yanling2 WANG ; Xiaobao2 QI ; Wenhui1 ZHANG ; Hong1 LIU
Journal of Clinical Hepatology 2021;37(5):1142-1146.
ObjectiveTo investigate the influencing factors for the clinical effect of emergency endoscopic therapy in the treatment of patients with acute-on-chronic liver failure and gastroesophageal variceal bleeding. MethodsA total of 51 patients with acute-on-chronic liver failure and gastroesophageal variceal bleeding who underwent emergency endoscopic therapy in Beijing Shijitan Hospital and The Fifth Medical Center of Chinese PLA General Hospital from January 2016 to December 2018 were enrolled, among whom 26 had successful hemostasis and 25 had failed hemostasis. The two groups were compared in terms of general information, varices grade and bleeding manifestations under endoscope, blood biochemical parameters, ultrasound findings, Child-Pugh class, and Model for End-Stage Liver Disease (MELD) score, and the influencing factors for the outcome of hemostasis were analyzed. The t-test or the Mann-Whitney U test was used for comparison of continuous data between two groups, and the chi-square test was used for comparison of categorical data between two groups; the logistic regression model was used to perform the multivariate analysis. ResultsOf all patients, 26 achieved successful hemostasis, with a success rate of hemostasis of 51%. There were no significant differences between the two groups in sex, age, etiology of liver cirrhosis, presence or absence of liver cancer, presence or absence of portal vein thrombosis, bleeding for the first time or not, white blood cell count, hemoglobin, platelet count, prothrombin time activity, alanine aminotransferase, total bilirubin, albumin, cholinesterase, MELD score, and bleeding site and bleeding manifestations under gastroscope (all P>0.05). Compared with the failed hemostasis group, the successful hemostasis group had a significantly longer course of disease (t=2.760, P=0.008) and significantly larger portal vein diameter and diameter of varicose veins under endoscope (t=-4.847, χ2=-6.590, both P<0.05), and the failed hemostasis group had a significantly higher proportion of patients with Child-Pugh class C disease than the successful hemostasis group (χ2=5.684, P=0.017). Course of liver cirrhosis (odds ratio [OR]=0.913, 95% confidence interval [CI]: 0.838-0.994, P<0.05), portal vein diameter (OR=1.925,95%CI: 1.516-2.443, P<0.05), and diameter of varicose veins (OR=23.254, 95%CI: 2.250-240.352, P<0.05) were independent influencing factors for the clinical effect of endoscopic hemostasis. ConclusionThere is a relatively low success rate of emergency endoscopic hemostasis in patients with acute-on-chronic liver failure, and course of liver cirrhosis, portal vein diameter, and diameter of varicose veins are independent influencing factors for the clinical effect of endoscopic hemostasis.
3.Predictive research of 5-hydroxytryptamine in severity of severe community-acquired pneumonia
Quan1 HE ; Dan-Yu2,3 LIU ; Jun1 YE ; Yan-Li1 ZHANG ; Hua-Dong2 ZHU ; Cheng-Yu1* JIANG ; Jun2* XU
Basic & Clinical Medicine 2020;40(9):1195-1200
Objective To search for potential prognostic markers for severe community-acquired pneumonia(SCAP)using non-targeted metabolomics. Methods Testing plasma samples from 30 healthy people and 68 SCAP patients (all collected from January 2015 to June 2019 at Peking Union Medical College Hospital) by liquid chromatography mass spectrometry(LC-MS ).According to clinical prognosis,patients were divided into survive group (n=49)and non-survive group(n=19).OPLS-DA(multivariate statistical analysis)and Kruskal Wallis Test (single variable statistical analysis) were used to identify differential metabolites. Correlation analysis of clinical indicators and prognostic analysis were also used for differential metabolites. Results Totally 3463 metabolites were detected in healthy people and SCAP patients by LC-MS. Among them, 126 metabolites were screened out by OPLS-DA andKruskal Wallis Test analysis methods. Prognostic analysis showed that the quantity of 5-hydroxytryptamine(5-HT) was significantly different between survive group and non-survive group(P<0.05,AUC>0.75).Correlation analysis of clinical indicators showed that 5-HT was positively correlated with oxygenation index (OI) and negatively cor-related with acute physiology and chronic health evaluation(APACHE II)score. Conclusions The 5-HT as a potential prognostic marker for SCAP,may predict the prognosis of SCAP patients.
4.Expression of integrin-lined kinase in esophageal squamous cell carcinoma tissues and its effect on proliferation and apoptosis of KYSE-150 cells and the growth of xenografts in nude mice
MA Xiaoli1 ; GAO Yan1 ; WEI Yu1 ; CAO Leiyu1 ; ZHANG Zhouhua2, ; ZHANG Li1
Chinese Journal of Cancer Biotherapy 2022;29(6):549-556
[摘 要] 目的:分析整合素连接激酶(ILK)基因在食管鳞状细胞癌(ESCC)组织中的表达水平及其与患者临床病理特征之间的关系,探讨其对KYSE-150细胞增殖、凋亡和裸鼠皮下移植瘤生长的影响。方法:选取2012年1月至2014年12月手术切除并经病理证实的75例ESCC患者的癌组织和其配对的癌旁组织标本,用组织芯片技术及免疫组织化学染色法检测ESCC组织和癌旁组织中ILK的表达情况;qPCR法检测ESCC细胞ECA109、TE-1、EC9706、KYSE-150中ILK mRNA的表达,选用ILK表达最高的KYSE-150细胞进行后续细胞功能学研究。使用ILK干扰慢病毒感染KYSE-150细胞下调ILK的表达,qPCR和WB法检测ILK基因敲降效率;MTT实验、克隆形成实验和FACS检测干扰ILK表达对KYSE-150细胞增殖能力和凋亡水平的影响;裸鼠皮下成瘤实验检测干扰ILK对KYSE-150细胞移植瘤生长的影响。结果:ESCC组织中ILK蛋白阳性表达率高于癌旁组织(P<0.05),且ILK高表达与淋巴结转移有关联(P<0.05)。ILK干扰慢病毒感染的KYSE-150细胞中ILK mRNA表达明显受到抑制(P<0.05),ILK蛋白水平表达下调,以上结果提示ILK敲降成功。与感染阴性对照病毒的KYSE-150细胞相比,ILK干扰慢病毒感染的KYSE-150细胞的增殖能力、克隆形成数均显著降低(均P<0.05),但细胞凋亡率升高(P<0.05)。与对照组相比,干预组裸鼠移植瘤生长缓慢,移植瘤的质量及体积均较小(均P<0.05)。结论:ESCC组织中ILK的表达高于癌旁组织,且ILK高表达与患者发生淋巴结转移有关联;抑制ILK基因可导致KYSE-150细胞增殖能力降低,促进细胞凋亡而抑制裸鼠移植瘤生长。
5.Expression and clinical significance of E3 ubiquitin ligase HECW2 in gastric adenocarcinoma tissues
LI Fang1 ; SHEN Hui1 ; WANG Xiaofei2 ; WANG Li1 ; HAN Caili1 ; LIU Junli1 ; ZHANG Jing1
Chinese Journal of Cancer Biotherapy 2022;29(9):813-821
[摘 要] 目的:采用生物信息学方法分析E3泛素连接酶(HECW2)在胃腺癌组织中的表达及其临床意义,为寻找胃腺癌诊断和预后生物标志物提供新的线索。方法:用R语言分析HECW2在泛癌中的表达及其与泛癌预后的关系。借助UCSC Xena、HPA、Kaplan-Meier Plotter等数据库分析HECW2在胃腺癌组织中的表达及其与临床病理特征之间的关系。采用WB法检测中国人胃腺癌组织及其癌旁组织中HECW2蛋白水平以验证数据库中的分析结果。借助TIMER和Cibersort数据库分析HECW2与胃腺癌免疫浸润的关系。通过LinkedOmics数据库对胃腺癌中HECW2进行GO功能分析和KEGG信号通路富集分析及相关性基因分析。结果:生物信息学分析结果表明,33种不同类型肿瘤中,包括胃腺癌在内的12种肿瘤中HECW2呈显著高表达(均P<0.05),WB法结果显示,中国人胃腺癌组织中HECW2也呈显著高表达(P<0.05)。HECW2表达水平越高,胃腺癌患者OS越短,包括CD4+ T细胞、巨噬细胞、中性粒细胞和树突状细胞在内的免疫细胞浸润丰度越高(均P˂0.01)。此外,HECW2相关信号通路主要富集于细胞外基质受体相互作用、黏着斑、细胞黏附和氧化磷酸化等生理病理过程(均P˂0.01)。结论:HECW2在胃腺癌组织中呈显著高表达且其与胃腺癌预后不良和免疫细胞浸润密切相关,有成为胃腺癌预后标志物和治疗靶点的潜力。
6.Observation on the effect of adoptive immunotherapy with activated autologous lymphocytes in the treatment of primary hepatocellular carcinoma
YANG Yanli1 ; LIAO Li1 ; ZHANG Jing1 ; SUN Peng1 ; TAKASHIMA Kenichi2 ; YANG Yuhui2 ; ZHANG Bin1 ; HU Liangding1
Chinese Journal of Cancer Biotherapy 2021;28(11):1098-1106
[摘 要] 目的:评价活化自体淋巴细胞过继性免疫治疗(adoptive immunotherapy,AIT)是否有助于改善原发性肝细胞癌的临床疗效。方法:选取2016年8月至2018年12月在中国人民解放军总医院第五医学中心确诊的64例原发性肝细胞癌患者,通过分层随机法分为免疫治疗组(n=29)和对照组(n=35)。免疫治疗组患者取60 ml外周血分离制备单个核细胞并在含OKT-3和IL-2的培养基中活化培养,回输前进行质控检测。免疫治疗组中的Ⅰ~Ⅲ期患者(n=14)于一线治疗后接受自体淋巴细胞输注(3个月内输注6次),Ⅳ期患者(n=15)仅接受自体淋巴细胞输注;对照组患者接受肝细胞癌相关的其他治疗。疗效评估的主要终点是2年无复发生存(relapse-free survival,RFS)率,次要终点为无进展生存期(progression-free survival,PFS)和总生存期(overall survival,OS)。结果:入组患者中位随访时间为2.8年(0.2~4.2年)。免疫治疗组29名患者共接受了167次(计划174次,完成率96%)预定淋巴细胞输注(平均每人次回输9.30×109个细胞,其中CD3+HLA-DR细胞约占63%),治疗期间未观察到3级或4级不良反应发生。与对照组相比,免疫治疗组患者2年RFS率显著升高(62.1% vs 22.9%,OR=0.181,95%CI:0.06~0.54,P=0.002),中位PFS(28 vs 8个月,P=0.004)和中位OS(38 vs 34个月,P=0.915)均显著延长。在Ⅰ~Ⅲ期患者中,免疫治疗组(n=14)2年RFS率较对照组(n=18)显著升高(92.9% vs 33.3%,OR=0.38,95%CI:0.004~0.368,P=0.005),中位PFS明显延长(38 vs 14.5个月,P=0.005),而两组OS间无显著差异;Ⅳ期患者两组间PFS(P=0.077)及OS(P=0.994)均未见显著差异。结论:活化自体淋巴细胞AIT为安全可行的肝细胞癌辅助性治疗方法,可提高Ⅰ~Ⅲ期肝细胞癌一线治疗后RFS率、延长患者RFS时间,而对进展期肝细胞癌患者的PFS和OS无明显影响。