Mutation profile and its correlation with clinicopathology in Chinese hepatocellular carcinoma patients

BackgroundHepatocellular carcinoma (HCC) is one of the most common causes of cancer worldwide. Although many studies have focused on oncogene characteristics, the genomic landscape of Chinese HCC patients has not been fully clarified.MethodsA total of 165 HCC patients, including 146 males and 19 females, were enrolled. The median age was 55 years (range, 27–78 years). Corresponding clinical and pathological information was collected for further analysis. A total of 168 tumor tissues from these patients were selected for next-generation sequencing (NGS)-based 450 panel gene sequencing. Genomic alterations including single nucleotide variations (SNV), short and long insertions and deletions (InDels), copy number variations, and gene rearrangements were analyzed. Tumor mutational burden (TMB) was measured by an algorithm developed in-house. The top quartile of HCC was classified as TMB high.ResultsA total of 1,004 genomic alterations were detected from 258 genes in 168 HCC tissues. TMB values were identified in 160 HCC specimens, with a median TMB of 5.4 Muts/Mb (range, 0–28.4 Muts/Mb) and a 75% TMB of 7.7 Muts/Mb. The most commonly mutated genes were TP53, TERT, CTNNB1, AXIN1, RB1, TSC2, CCND1, ARID1A, and FGF19. SNV was the most common mutation type and C:G>T:A and guanine transformation were the most common SNVs. Compared to wild-type patients, the proportion of Edmondson grade III–IV and microvascular invasion was significantly higher in TP53 mutated patients (P<0.05). The proportion of tumors invading the hepatic capsule was significantly higher in TERT mutated patients (P<0.05). The proportion of Edmondson grade I-II, alpha fetoprotein (AFP) <25 µmg/L, and those without a history of hepatitis B was significantly higher in CTNNB1 mutated patients (P<0.05). CTNNB1 mutations were associated with TMB high in HCC patients (P<0.05). Based on correlation analysis, the mutation of TP53 was independently correlated with microvascular invasion (P=0.002, OR =3.096) and Edmondson grade III–IV (P=0.008, OR =2.613). The mutation of TERT was independently correlated with tumor invasion of the liver capsule (P=0.001, OR =3.030), and the mutation of CTNNB1 was independently correlated with AFP (<25 µmg/L) (P=0.009, OR =3.414).ConclusionsThe most frequently mutated genes of HCC patients in China were TP53, TERT, and CTNNB1, which mainly lead to the occurrence and development of HCC by regulating the P53 pathway, Wnt pathway, and telomere repair pathway. There were more patients with microvascular invasion and Edmondson III–IV grade in TP53 mutated patients and more patients with hepatic capsule invasion in TERT mutated patients, while in CTNNB1 mutated patients, there were more patients with Edmondson I–II grade, AFP <25 µmg/L, and a non-hepatitis B background. Also, the TMB values were significantly higher in CTNNB1 mutated patients than in wild type patients.     

知识模式转换在医学科技创新中的作用

医学科技创新是医院赖以生存与发展的动力,医学科技创新的过程也是医学知识模式不断转换的过程,本文从知识模式转换的视角,探讨知识管理对医学科技创新的意义与作用     

骨质疏松研究的现状与展望

目前 ,我国骨质疏松的研究方兴未艾。 2 0 0 1年6月份成立了中华医学会骨质疏松和骨矿疾病分会 ,标志着我国骨代谢的研究进入了一个新阶段。骨质疏松是以骨强度降低和骨折危险性增加为特征的一种全身性骨疾病。骨强度主要取决两个因素 :骨密度和骨质量。骨密度用单位面积或体积的矿物盐克数表示 ,而影响骨质量的因素包括骨微结构、骨转化、损伤积累 (如微骨折 )和骨的矿化状况等。骨强度的降低使骨在遭受外力时易发生骨折。一、骨质疏松已引起了社会全方位的关注骨质疏松是一个世界范围的、日趋严重的影响健康的重要问题。资料显示 ,美国、…     

艾恒、丝裂霉素、氟尿嘧啶辅以醛氢叶酸联合化疗治疗转移性胃癌的临床研究

目的：评价国产草酸铂（艾恒）,丝裂霉素,氟尿嘧啶辅以CF治疗转移性胃癌的临床效及其毒副反应,方法：23例转移性胃癌患者接受L－OHP（艾恒）130mg/m^2,静滴,第1天,MMC10mg/m^2,静脉冲注,第1天,CF130mg/m^2,静滴,第1－5天,5－Fu 500mg,静脉注射,500mg静滴（6－8h),第1－5天,第21天为一周期,连用两个周期。结果：总缓解率为65．2％（15／23）,完全缓解率（CR）17．4％（4／23）,部分缓解率（PR）47．8％（11／23）,毒性反应主要是白细胞减少,发生率为43．4％,但3度以上者仅为4．3％,血红蛋白及血小板降低分别为21．7％和26．0％,口唇、面部、指端感觉迟钝,麻木,遇冷加重发生率较高达60．11％,其他毒性反应较少。结论：国产草酸铂（艾恒）为主组成的LMF／CF方案治疗转移性胃癌疗效较好,毒副作用较小。     

逆转录病毒介导的HSV-TK基因对人骨肉瘤细胞的杀伤作用

目的 探讨骨肉瘤基因治疗的可行性。方法 采用逆转录病毒介导的HSV-TK基因转移和GCV治疗的方法进行研究。结果 成功构建含HyTK基因的重组逆转录病毒载体DORHyTK;采用DOTAP将其转入PA317细胞中进行包装,筛选,并进行病毒滴度测定。收获病毒上清体外感染骨肉瘤细胞株OS732和SAOS-2。分别用PCR和RNA斑点杂交的方法证明假病毒中不含有复制活性病毒,HSV-TK基因已整合到宿主细胞基因组中,并获得表达,MTT比色法测定结果显示GCV对OS732TK和SAOS-2TK细胞均有明显的杀伤作用。且前者强于后者,旁观者效应在高细胞密度接种条件下强于低细胞密度,在SAOS-2细胞中的作用强于OS732。结论 HSV-TK/GCV基因治疗系统可为骨肉瘤的治疗提供新途径。     

红皮病63例临床分析

目的：分析红皮病的病因。方法：对63例红皮病住院病人进行回顾性分析。结果：继发于其它皮肤言不由衷的患者占73.02%,其它依次为药材物过敏、肿瘤和原因不明,其中寻常型银屑病是最常见的原发性疾病。结论：寻找红皮病的病因有助于指导治疗。     

银屑病患者血清及尿中表皮生长因子的检测及意义

目的：评价表皮生长因子（EGF）在银屑病发病中的意义。方法：应用放射免疫法分别检测血清及尿液中EGF含量。结果：银屑病患者血清及尿液中EGF均显著升高。结论：EGF在银屑病初次发病及复发中起着重要的作用。     

二尖瓣-主动脉瓣置换术近期和远期效果的评价

目的 :评价单瓣与双瓣置换术的近期与远期效果。方法 :70例风湿性心脏病人采用国产上海碟瓣行机械瓣置换术 ,其中单纯行二尖瓣 (MV)置换术者 47例 ,二尖瓣加主动脉瓣 (AV)双瓣置换术者 2 3例。生存者 10 0 %随访 1～ 7年 (平均 4.76± 1.7年 )。结果 :院内死亡 4例 ,死亡率为 5 .71%。随访中死亡 2例 ,远期死亡率为 0 .63 %人·年。 7年生存率为 95 .69% ,10年生存率为 93 .89%。 94.0 0 %术后心功能均改善Ⅰ～Ⅱ级。结论 :房颤 (Af)并Ⅱ度房室传导阻滞的病人应暂缓手术 ;国产上海碟瓣有良好的血流动力学特性 ;只要处理恰当 ,双瓣手术的危险性不比单瓣手术的危险性高。     

上颌骨骨纤维异常增殖症19例报告

目的：探讨上颌骨骨纤维异常增殖症的临床特征、诊断及治疗。方法：对１９８７至１９９７年收治的１９ 上凳骨骨纤维异常增殖症患者的临床资料进行回顾性分析。结果：本病好发于青少年凤无痛性颌面部膨胀畸形和邻近器官功能障碍为主要症状,Ｘ线片示病变区骨质呈不同程度磨玻璃样外观,边界不清,采用局部保守切除和骨创面冷冻治疗,１７例随访２￣１０年无复发,另２例复发再次手术治愈。结论：根据病史,体征及Ｘ线检查可作出诊断     

氨氯地平与非洛地平缓释剂治疗原发性轻、中度高血压的随机、双盲平行对照研究

目的:对比氨氯地平与非洛地平缓释剂治疗轻中度原发性高血压的疗效和安全性;每日1次服药对24小时动态血压的影响;并对比药物漏服对血压控制的影响。方法:76例轻、中度高血压患者被随机、双盲分成两组,分别每日口服1次氨氯地平5～10mg(Ⅰ组)或非洛地平缓释剂5～10mg(Ⅱ组),治疗12周,并用24小时动态血压监测评价用药前后24小时血压变化情况及漏服48小时的血压变化。结果:氨氯地平治疗组舒张压降低15.1mmHg(治疗末为84.8mmHg),非洛地平缓释剂治疗组舒张压降低15.3mmHg(治疗末为85.0mmHg)。总有效率Ⅰ组病人为83.8％,Ⅱ组为87.9％(P=NS)。在药物的初始剂量下即能达到有效血压控制的病人数Ⅰ组为76％,Ⅱ组为52％(P<0.01)。药物漏服24和48h后,Ⅰ组临床血压仍低于140/90mmHg,24小时动态血压与漏服前相比无显著性差异,而Ⅱ组的临床血压高于140/90mmHg,临床血压和24小时动态血压与漏服前相比具有显著性差异。两治疗组的副作用发生率均较低。结论:氨氯地平与非洛地平缓释剂均能有效降低轻、中度高血压病人的血压,安全、疗效可靠,病人耐受性好,但漏服试验表明漏服24与48h氨氯地平仍能较好的控制血压。Ⅰ组的血压波动明显低于Ⅱ组。