原发性肝癌组织中长链非编码RNA外泌体复合物7的表达及临床意义

目的探讨长链非编码RNA外泌体复合物7(LncRNA EXOC7)在原发性肝癌组织中的表达及临床意义。方法收集于宣城市中心医院2010年1月-2014年1月行肝癌手术患者的肝癌组织及其癌旁组织标本79对,采用real-time PCR分别检测肝癌组织和癌旁组织中LncRNA EXOC7的表达情况,分析其与病理特征和预后的关系。计量资料2组间比较采用t检验,计数资料2组间比较采用χ2检验或Fisher确切概率法,术后患者的生存分析采用Kaplan-Meier方法,使用Cox模型分析影响预后的危险因素。结果 LncRNA EXOC7在肝癌组织中表达水平明显高于癌旁组织(6. 211±0. 637 vs 2. 924±0. 415,t=4. 106,P 0. 01)。肿瘤大小(χ2=5. 157,P=0. 023)、有无门静脉癌栓(χ2=4. 049,P=0. 044)、有无脏器转移(χ2=4. 345,P=0. 037)和TNM分期(χ2=6. 479,P=0. 011)在LncRNA EXOC7高表达和低表达组间差异均有统计学意义。LncRNA EXOC7高表达组的无瘤生存期(χ2=8. 215,P 0. 001)和总体生存期(χ2=6. 091,P=0. 001)较低表达组短。Cox回归分析显示LncRNA EXOC7表达、肿瘤大小、脏器转移和TNM分期是影响原发性肝癌预后的独立因素(P值均0. 05)。结论 LncRNA EXOC7参与调节原发性肝癌的发生发展,有望成为一种新的肝癌预后参考指标。     

肝细胞肝癌组织中miR-21表达水平及与预后的相关性

目的探讨肝细胞肝癌患者组织中miR-21的表达水平及其预后意义。方法共收集50例肝细胞肝癌的患者,采用免疫组化法检测肝细胞肝癌及配对癌旁组织中miR-21的表达水平,分析miR-21蛋白的表达与患者临床病理特征及预后生存的相关性。结果肝细胞肝癌组织中miR-21表达水平显著高于癌旁组织(58.0%vs 6.0%,χ~2=31.07,P0.000 1)。miR-21高表达与临床T分期相关(χ~2=8.043,P=0.018);但miR-21蛋白表达水平与患者年龄、性别、肿瘤大小、临床分期、N分期及分化程度均无显著关联(P0.05)。高表达miR-21的肝细胞肝癌患者总生存时间明显降低(P=0.032),但患者无疾病进展生存期差异无统计学意义(P=0.116)。结论肝细胞肝癌患者miR-21高表达可能作为肿瘤患者预后不良的重要标志物之一,而与肿瘤的发生及发展的机制性研究尚需进一步验证。     

MicroRNA-34a、Notch1在肝细胞肝癌组织中的表达及临床意义

目的:观察microRNA-34a、Notch1在肝细胞肝癌(hepatocellular carcinoma,HCC)组织的表达,探讨其与HCC发生、发展、临床病理特征的关系及可能的临床意义.方法:在132例HCC组织及癌旁组织、49例正常肝脏组织中应用实时荧光定量PCR法检测microRNA-34a的表达和免疫组织化学染色检测Notch 1表达.结果:HCC组织中microRNA-34a表达水平明显低于癌旁组织(2.57±0.71,P=0.003)及正常肝组织(8.65±0.21,P<0.001),在转移性癌组织中microRNA-34a表达水平明显低于非转移性癌组织(1.34±0.13,P=0.014),差异均有统计学意义.Notch1的免疫组织化学染色结果:HCC组织中Notch1表达水平明显高于癌旁组织(3.12±0.67,P=0.001)及正常肝组织(4.65±0.14,P<0.001),转移性癌组织高于非转移性癌组织(2.14±0.37,P=0.008),差异有统计学意义.MicroRNA-34a与Notch1在HCC及癌旁组织中均成负相关,相关系数分别为(r=-0.259,P=0.003)、(r=-0.274,P=0.002),两者在HCC组织中的表达与患者年龄、性别、肝功能、肿瘤部位、是否合并肝硬变、是否伴随肝炎病毒感染及甲胎蛋白(α-fetoprotein,αFP或AFP)含量无相关性(P>0.05),而与肿瘤恶性程度、肿瘤个数、肿瘤体积、淋巴结转移、浸润深度、TNM分期密切相关(P<0.05).Kaplan-Meier分析显示:microRNA-34a低表达、Notch1高表达组患者术后3年生存率(11.3%),明显低于microRNA-34a高表达、Notch1低表达组(34.7%),差异具有统计学意义(χ2=38.163,P=0.011).结论:MicroRNA-34a在HCC组织中较癌旁和正常肝脏组织明显减低,其通过逆向调节靶蛋白Notch1参与肿瘤肿瘤恶性行为;检测microRNA-34a及Notch1在HCC组织中的表达情况,对HCC的临床诊断、治疗及预后判断有潜在的重要意义.     

胃癌患者CD151表达水平及其临床意义

目的探讨胃癌患者CD151表达水平及其临床意义。方法收集49例胃腺癌患者,采用免疫组化法检测胃癌及癌旁组织CD151表达水平,进而分析其与患者临床病理特征及长期预后的相关性。结果胃癌组织CD151表达水平明显高于癌旁组织(38.78%vs 6.12%)(χ2=17.515,P<0.001)。CD151高表达患者年龄明显小于低表达者,CD151表达水平与T分期有关(χ2=11.545,P=0.05)。CD151高表达胃癌患者总生存率明显差于CD151低表达者(P=0.039),而无疾病生存率两者无显著性差异(P=0.096)。结论胃癌患者CD151高表达可能提示肿瘤侵袭能力的增强,并与患者低总生存率有关。     

肝癌组织中Vasohibin1和HIF-1α表达及临床意义

目的研究肝癌组织中血管生成抑制蛋白(Vasohibin1)和缺氧诱导因子-1α(HIF-1α)的表达及两者的相关性,并探讨其临床意义。方法随机收集64例原发性肝细胞肝癌手术患者的癌组织,另选其中的26例癌旁组织作为对照组,应用免疫组织化学法检测Vasohibin1与HIF-1α在肝癌组织与癌旁组织中的表达特征并进行评分,进一步分析二者间的相关性及与肝癌患者临床病理特征间的关系。结果肝细胞肝癌组织中Vasohibin1和HIF-1α表达升高,与癌旁组织比较差异有统计学意义(χ2=20.19,P=0.00;χ2=5.147,P=0.023)。结合肝癌患者临床病理特征的统计分析表明,Vasohibin1的高表达与肝癌各临床病理参数在统计学上无明显相关性(P>0.05),HIF-1α的高表达与有无肿瘤转移有关(χ2=4.882,P=0.027),并且肝癌组织中二者的表达在统计学上有相关性(r=0.481,P=0.00)。结论 Vasohibin1和HIF-1α在肝癌组织高表达,提示二者在肝癌发生发展过程中发挥作用;二者的表达相关性提示它们之间可能以VEGF作为纽带或者存在相互作用。     

TEM7在胃癌组织和癌旁组织表达及其与患者临床病理特征的关系

目的 探讨肿瘤血管内皮标志物(TEM)7在胃癌组织和癌旁组织中表达及其与患者临床病理特征及预后的关系。方法 选取行胃癌根治术的胃癌患者122例,采用免疫组织化学染色法检测TEM7在胃癌组织和癌旁正常组织中表达,分析TEM7表达与临床病理特征及预后的关系。结果 胃癌组织中TEM7阳性表达率显著高于癌旁正常组织(χ²=21.252,P<0.001)。TEM7阳性表达与肿瘤分化程度、肿瘤浸润胃壁、临床分期及淋巴结转移有关(P<0.05),与患者性别、年龄、癌变部位、肿瘤直径及术后是否辅助治疗无关(P>0.05)。生存曲线显示,TEM7阳性表达患者中位无进展生存时间显著短于TEM7阴性表达患者(Log-rankχ²=8.820,P=0.003);TEM7阳性表达患者总生存时间显著短于TEM7阴性表达患者(Log-rankχ²=5.506,P=0.019)。Cox比例风险回归分析显示,TEM7阳性表达是胃癌患者术后总生存期和无进展生存期的独立风险因素(HR=4.178、5.613,95%CI为1.654～10.8...     

非小细胞肺癌中IGF1、IGFBP2表达与预后的相关性分析

目的探讨非小细胞肺癌组织胰岛素样生长因子1(IGF1)、胰岛素样生长因子结合蛋白2(IGFBP2),蛋白表达与患者临床病理特征及预后的关系。方法将226例确诊的非小细胞肺癌患者癌组织为非小细胞肺癌组;选取其癌旁正常组织为癌旁对照组。检测癌组织及癌旁正常组织IGF1、IGFBP2蛋白表达水平;分析非小细胞肺癌患者癌组织IGF1与IGFBP2蛋白表达相关性及其与预后的关系;并分析影响非小细胞肺癌患者预后的因素。结果非小细胞肺癌组IGF1、IGFBP2蛋白高表达率高于癌旁对照组(P<0.05)。非小细胞肺癌患者癌组织IGF1、IGFBP2蛋白表达与肿瘤大小、淋巴结转移、组织分化程度、TNM分期有关(P<0.05)。非小细胞肺癌患者癌组织IGF1与IGFBP2蛋白表达呈正相关(r=0.472,P<0.05)。IGF1、IGFBP2高表达患者五年生存率(33.33%、29.41%)低于低表达患者(69.23%、73.33%)(P均<0.05)。IGF1高表达、IGFBP2高表达、TNMⅢ~Ⅳ期是影响非小细胞肺癌患者死亡的独立危险因素(P<0.05)。结论IGF1、IGFBP2可能在非小细胞肺癌发生发展过程中发挥重要作用,且IGF1、IGFBP2高表达与患者不良预后有关。     

胰腺癌组织中L1细胞黏附分子和转化生长因子β1的表达及意义

目的探讨分析L1细胞黏附分子(L1CAM)和转化生长因子β1(TGFβ1)在胰腺癌组织中的表达及其与预后的关系。方法选取2015年1月—2018年1月于广西医科大学第一附属医院、广西医科大学附属肿瘤医院、广西医科大学附属武鸣医院行手术切除的125例胰腺癌患者的组织学标本。采用免疫组化法检测所有标本L1CAM(高表达组94例,低表达组31例)和TGFβ1(高表达组102例,低表达组23例)表达情况,并分析二者表达与临床指标、生存预后的关系。计量资料2组间比较采用t检验;计数资料2组间比较采用χ~2检验。采用Cox风险比例模型分析胰腺癌患者生存的影响因素; Kaplan-Meier生存分析评估不同L1CAM、TGFβ1表达水平患者的生存情况,log-rank进行检验。结果胰腺癌组织L1CAM蛋白高表达率为75.20%,明显高于癌旁组织L1CAM蛋白高表达率(20.00%),差异有统计学意义(χ~2=76.352,P 0.001)。胰腺癌组织TGFβ1蛋白高表达率为81.60%,明显高于癌旁组织TGFβ1蛋白高表达率(23.20%),差异有统计学意义(χ~2=85.461,P 0.001)。L1CAM和TGFβ1蛋白在胰腺癌组织中的表达呈正相关,差异有统计学意义(r=0.492,P 0.001)。L1CAM和TGFβ1蛋白表达均与肿瘤大小、分化程度、TNM分期、淋巴结转移、脉管内癌栓和神经侵犯有关(P值均0.05)。L1CAM或TGFβ1蛋白高表达患者总生存率明显低于低表达患者,差异均有统计学意义(χ~2值分别为54.661、39.597,P值均0.001)。结论 L1CAM蛋白和TGFβ1蛋白在胰腺癌组织中高表达,其对不良预后的影响可能与其促进淋巴道转移、血行转移等因素有关,二者在胰腺癌发生发展及转移过程中发挥着重要作用。     

基于生物信息学分析核仁纺锤体相关蛋白1在肝细胞癌中的表达及对临床预后的影响

目的探讨在肝癌中核仁纺锤体相关蛋白1(NUSAP1)的表达及其对临床预后的影响。方法从基因表达数据库(GEO)下载HCC芯片数据集GSE57957、GSE14520、GSE22058、GSE46444、GSE54236、GSE36376、GSE64041、GSE76297、GSE76427、GSE102079和癌症基因组图谱(TCGA)中的HCC RNA-seq数据,利用R 4.0软件分析NUSAP1在肝癌及癌旁组织的表达差异。应用t-分布邻域嵌入算法(tSNE)对单细胞测序数据的降维,分析NUSAP1在肝癌和癌旁组织中的差异表达。收集2018年1月—2019年11月在青岛大学附属医院进行同种异体肝移植术的42例乙型肝炎相关肝癌患者的癌组织及癌旁组织,收集其临床病理资料并分析与NUSAP1基因表达的相关性。计数资料2组间比较采用χ~2检验。以Kaplan-Meier方法生存分析NUSAP1表达水平与总体生存率及无病间隔生存率之间的关系,运用log-rank进行检验,通过Graphpad prim 7使其结果可视化。结果 NUSAP1在GEO数据库与TCGA数据库数据集中的肝癌组织中均高表达(P值均0.001)。来源于肿瘤组织的细胞其NUSAP1高表达细胞明显高于癌旁组织细胞。NUSAP1在29例患者的肝癌组织中高表达,在13例患者的肝癌组织中低表达,NUSAP1在肝癌组织中高表达组及低表达组间,Child-Pugh分级、TNM分期、Okuda分期比较差异均有统计学意义(χ~2值分别为5.469、6.836、4.617,P值均0.05)。NUSAP1高表达的肝癌患者总体生存率与无病间隔生存率显著低于低表达的肝癌患者,NUSAP1低表达患者1、3、5生存率分别为92.96%、83.80%、76.76%,明显高于高表达的患者(76.76%、67.60%、64.78%),NUSAP1高表达的患者中位生存时间明显低于低表达的患者(61.7个月vs 108.6个月)(P值均0.05)。结论 NUSAP1在肝癌细胞中高表达,可作为乙型肝炎肝癌患者不良预后的潜在标志物。     

神经前体细胞表达下调蛋白9在胰腺癌组织中的表达及临床意义

目的检测神经前体细胞表达下调蛋白(NEDD)9在胰腺癌和癌旁组织的表达情况,分析其与胰腺癌进展、预后的关系。方法收集2005年8月-2010年12月于无锡市第三人民医院治疗的98例胰腺癌患者的癌和癌旁组织样本,应用免疫组化技术检测患者胰腺癌和癌旁组织中NEDD9的表达,并对NEDD9表达与胰腺癌临床病理特征的关系进行分析。计数资料组间比较采用χ2检验。结果胰腺癌组织中NEDD9的高表达率明显高于癌旁组织(57.1%vs 41.8%,χ2=4.592,P=0.032)。胰腺癌组织NEDD9的表达与患者TNM分期、分化程度及有无淋巴结转移相关(χ2值分别为45.02、20.41、36.21,P值均0.001);与性别、年龄、肿瘤部位、有无肝转移无相关性(P值均0.05)。结论 NEDD9可能在胰腺癌的发展和侵袭转移中起着一定的作用,有可能作为评估胰腺癌预后的分子指标和治疗靶点。     

Prognostic signif icance of HIF-2α/EPAS1 expression in hepatocellular carcinoma

AIM: To evaluate the prognostic signif icance of HIF- 2α/EPAS1 expression in hepatocellular carcinoma (HCC). METHODS: Surgical specimens from 315 patients with HCC as well as 196 adjacent noncancerous lesions and 22 cases of normal liver tissue were investigated by immunohistochemistry (IHC) for HIF-2α/EPAS1 using a standard detection system. Correlations with clinicopathological factors, VEGF, microvessel density (MVD), and prognosis were analyzed. RESULTS: Immunoreactivity of HIF-2α/EPAS1 was positive in 69.5% of HCC, 55.6% of adjacent noncancerous tissue, and 0% of normal liver tissue. And it was significantly correlated with tumor grade, venous invasion, intrahepatic metastasis, necrosis, and capsule infiltration. Correlation analysis of HIF-2α/EPAS1 with angiogenic factor VEGF (P < 0.001), and MVD (P = 0.016) was also noted. HIF-2α/EPAS1 protein was less frequently expressed in low MVD cases, whereas a high rate of expression was noted in cases with both medium and high MVD (P = 0.042). By Kaplan-Meier analysis, strong HIF-2α/EPAS1 staining (> 50% of tumor cells) in HCC correlated with a shortened survival in patients (Cox's regression, P < 0.001, r = 3.699). CONCLUSION: We conclude that HIF-2α/EPAS1 expression may play an important role in tumor progression and prognosis of HCC. Assessment of HIF-2α/EPAS1 expression in HCC may be used as a diagnostic tool and possibly a target in the treatment of HCC.     

Chemokine ligand 20 enhances progression of hepatocellular carcinoma via epithelial-mesenchymal transition

AIM: To identify the mechanisms of chemokine ligand 20(CCL20)-induced hepatocellular carcinoma(HCC) metastasis and evaluate it as a prognostic marker. METHODS: Expression of CCL20 was evaluated by immunohistochemistry in HCC tissues from 62 patients who underwent curative resection. The relationship between CCL20 expression and clinicopathologic features was analyzed. Univariate and multivariate analyses were performed to evaluate its predictive value for recurrence and survival of HCC patients. The expression levels ofepithelial-mesenchymal transition(EMT)-and signaling pathway-related proteins were evaluated by Western blotting and immunocytochemistry. The effects of CCL20 on HCC cell proliferation and migration were analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenoltetrazolium bromide(MTT) and Transwell assays. RESULTS: CCL20 immunoreactivity was detected in all 62 patient specimens. CCL20 expression was associated with preoperative alpha-fetoprotein level(P = 0.043), tumor size(P = 0.000), tumor number(P = 0.008), vascular invasion(P = 0.014), and tumor differentiation(P = 0.007). Patients with high CCL20 expression had poorer recurrence-free and overall survivals compared to those with low CCL20 expression(both P 0.001). CCL20 induced EMT-like changes in HCC cells and increased their proliferation and migration ability(P 0.05). Western blotting and immunofluorescence staining showed that CCL20 induced an EMT-like phenotype in HCC cells, and increased expression of phosphorylated AKT, β-catenin and vimentin, and decreased E-cadherin expression(P 0.05). The correlation analysis revealed that high CCL20 expression in HCC tissue specimens was negatively correlated with E-cadherin expression(13.33%, 4/30), and positively correlated with vimentin(90.0%, 27/30), β-catenin(96.67%, 29/30) and p-AKT(76.67%, 23/30) expression.CONCLUSION: CCL20 expression is associated with HCC recurrence and patient survival and promotes HCC cell proliferation and migration by inducing EMT-like changes via PI3K/AKT and Wnt/β-catenin pathways.     

Overexpression of galectin-1 is associated with poor prognosis in human hepatocellular carcinoma following resection

Background and Aim: The high expression of the galectin‐1 predicts poor patient outcome in several tumors. The aim of this study was to investigate its prognostic value in patients with hepatocellular carcinoma (HCC) after resection. Methods: Galectin‐1 and tumor‐infiltrating FoxP3⁺ regulatory T cells (Tregs) were validated by tissue microarrays from HCC patients (n = 386) and statistically assessed for correlations with the clinical profiles and the prognosis of the patients. Results: We found that galectin‐1, which was prevalently upregulated in HCC, was significantly associated with tumor invasive characteristics (such as vascular invasion, incomplete encapsulation, poor differentiation, multiple number, and large tumor size). Patients with high galectin‐1 expression had a significantly poorer tumor recurrence (P = 0.025) and overall survival (P = 0.021) than those with low galectin‐1 expression. Even in early‐stage disease, high galectin‐1 expression was also independently associated with shortened survival (P < 0.001) and increased tumor recurrence (P = 0.005). Multivariate Cox proportional hazards analysis showed that galectin‐1 was an independent marker for predicting the poor prognosis of HCC. The galectin‐1 level was positively related to the number of tumor‐infiltrating FoxP3⁺ Tregs (r = 0.416, P < 0.001), and their combination served as a better prognosticator. The postoperative tumor recurrence and survival of HCC patients with galectin‐1^high and FoxP3^high were significantly poorer than the other groups (both P < 0.001). Conclusions: Galectin‐1 might be a new prognostic factor for HCC after resection and could potentially be a high‐priority therapeutic target.     

Neuron-glial antigen 2 overexpression in hepatocellular carcinoma predicts poor prognosis

AIM: To investigate whether neuron-glial antigen 2 (NG2) could be an effective prognostic marker in hepatocellular carcinoma (HCC).METHODS: NG2 expression was semi-quantitatively scored from the immunohistochemistry (IHC) data based on the number of positive cells and the staining intensity. A total of 132 HCC specimens and 96 adjacent noncancerous tissue samples were analyzed by IHC for NG2 protein expression. To confirm the NG2 expression levels observed by IHC, we measured NG2 expression in 30 randomly selected tumor and adjacent noncancerous tissue samples by quantitative real-time polymerase chain reaction and Western blot. The correlations between NG2 protein expression and the clinicopathological features of HCC patients were analyzed using the χ² test. To assess the prognostic value of NG2 for HCC, the association between NG2 expression and survival was analyzed using the Kaplan-Meier method with the log-rank test. To further evaluate the prognostic value of NG2 expression, a Cox multivariate proportional hazards regression analysis was performed with all the variables to derive risk estimates related to disease-free and overall survival and to control for confounders.RESULTS: High NG2 expression was observed in significantly more primary tumor samples (63.6%; 84/132) compared with the adjacent noncancerous tissue samples (28.1%; 27/96) (P < 0.0001). Moreover, high NG2 protein expression was closely associated with tumor differentiation (χ² = 9.436, P = 0.0089), recurrence (χ² = 5.769, P = 0.0163), tumor-node-metastasis (TNM) stage (χ² = 8.976, P = 0.0027), and invasion (χ² = 5.476, P = 0.0193). However, no significant relationship was observed between NG2 protein expression in HCC and other parameters, such as age, sex, tumor size, serum alpha fetoprotein (AFP), tumor number, or tumor capsule. The log-rank test indicated a significant difference in the overall survival of HCC patients with high NG2 expression compared with those with low NG2 expression (29.2% vs 9.5%, P < 0.001). Moreover, NG2 expression in HCC tissue significantly correlated with disease-free survival (15.2% vs 6.7%, P < 0.001). Multivariate analysis showed that NG2 expression (HR = 2.035, P = 0.002), serum AFP (HR = 1.903, P = 0.003), TNM stage (HR = 2.039, P = 0.001), and portal vein invasion (HR = 1.938, P = 0.002) were independent prognostic indicators for OS in HCC patients. Furthermore, NG2 expression (HR = 1.974, P = 0.003), serum AFP (HR = 1.767, P = 0.008), TNM stage (HR = 2.078, P = 0.001), tumor capsule (HR = 0.652, P = 0.045), and portal vein invasion (HR = 1.941, P = 0.002) were independent prognostic indicators for DFS in HCC patients.CONCLUSION: The up-regulation of NG2 is associated with poor prognosis in HCC. Therefore, NG2 could be useful as an additional prognostic marker to increase the resolution of traditional approaches.     

Transglutaminase 3 expression in hepatocellular carcinoma patients: Correlation with tumor features and survival profile

BackgroundTransglutaminase 3 (TGM3) regulates multiple oncogene pathways (GSK-3β/β-catenin pathway, Akt/ERK pathway, etc.) to promote hepatocellular carcinoma (HCC) cell proliferation, migration and invasion, however, its clinical value for HCC management is still limited. Therefore, we conducted this study to compare the TGM3 expression between tumor tissue and paired adjacent noncancerous tissue, aiming to explore the clinical application of TGM3 in HCC patients.MethodsTotally, 208 HCC patients were enrolled and their clinicopathological features were collected. Then, 208 pairs of HCC specimens and adjacent noncancerous specimens were used to detect TGM3 protein expression by IHC assay and assessed by a semi-quantitative scoring method. Besides, 157 pairs were proposed to detect TGM3 mRNA expression by RT-qPCR.ResultsBoth TGM3 protein (P<0.001) and mRNA (P<0.001) levels were increased in HCC specimens compared to adjacent noncancerous specimens. Besides, TGM3 high protein expression correlated with multifocal tumor nodules (P<0.001), advanced Barcelona Clinic Liver Cancer (BCLC) stage (P = 0.006), higher carcinoembryonic antigen (P = 0.038) and alpha-fetoprotein (AFP) (P<0.001). While TGM3 high mRNA expression correlated with multifocal tumor nodules (P = 0.025), largest tumor size ≥ 5.0 cm (P = 0.042) and higher AFP (P = 0.019). Furthermore, both TGM3 protein (P = 0.002) and mRNA (P = 0.028) high expressions correlated with shorter overall survival (OS). While after adjustment by multivariant Cox's regression, TGM3 protein high expression (vs. low) independently predicted worse OS (P = 0.004).ConclusionsTMG3 expression is increased in tumor tissue, also its high expression correlates with multiple tumor nodules, higher BCLC stage, abnormal AFP and reduced OS in HCC patients.     

Clinical utility of serum fucosylated hemopexin in Japanese patients with hepatocellular carcinoma

Aim: Hepatocellular carcinoma (HCC) is a common clinical problem all over the world. Fucosylated hemopexin (Fuc-Hpx) is a newly reported glycoprotein for the diagnosis of HCC, however, its clinical implications are unclear. The aim of this study was to elucidate the clinical utility of Fuc-Hpx in Japanese patients with HCC. Methods: The sera from 331 HCC patients, 45 with liver cirrhosis (LC), 85 with chronic hepatitis (CH) and 22 healthy people were examined for the expression of Fuc-Hpx; the level was compared with clinical parameters as well as hemopexin (Hpx) expression. The expressions of Fuc-Hpx in 12 HCC tissues and corresponding adjacent non-cancerous liver tissues were also examined. Results: No correlation was observed between Hpx and Fuc-Hpx level. The median Fuc-Hpx levels in healthy people and CH, LC and HCC patients were 3.8, 3.7, 6.1 and 7.6 AU/mL, respectively (CH vs LC, P = 0.002; CH vs HCC, P < 0.001; LC vs HCC, P = 0.02). Multivariate analysis revealed that low albumin, low prothrombin time and the presence of HCC were significantly correlated with high Fuc-Hpx (P = 0.013, =0.001 and <0.001, respectively). Among the HCC patients, albumin was correlated with high Fuc-Hpx; however, none of the tumor factors, such as tumor size, tumor number and tumor stage, was correlated with Fuc-Hpx level. The expression of Fuc-Hpx in cancer tissue was not different from that in non-cancerous tissue. Conclusion: Fuc-Hpx is a valuable biomarker for HCC but it might be a marker for hypercarcinogenic liver rather than a marker for tumor-bearing liver.     

肝细胞癌患者肝动脉化疗栓塞术后外周血长链非编码RNA TINCR水平与Th1/Th2平衡及预后的相关性分析

目的探讨分析外周血长链非编码RNA(lncRNA)TINCR表达水平与肝细胞癌(HCC)患者行肝动脉化疗栓塞术(TACE)术后辅助性T淋巴细胞1(Th1)/Th2平衡及预后的相关性。方法回顾性选取2015年3月—2017年3月在湖北省武汉市金银潭医院行TACE治疗的HCC患者85例,并随机抽取在本院体检的健康志愿者30例作为对照组。检测HCC患者TACE完成后7 d及对照组外周血lncRNA TINCR表达情况、Th1/Th2细胞因子表达情况。计量资料组间比较采用t检验,计数资料组间比较采用χ2检验,等级资料组间比较采用Kruskal-Wallis H检验。lncRNA TINCR相对表达量与Th1/Th2细胞因子的相关性采用Spearman相关性分析。lncRNA TINCR相对表达量对生存情况的影响采用Kaplan-Meier生存曲线分析,生存曲线比较采用log-rank检验。结果HCC组患者外周血lncRN TINCR相对表达量(1.784±0.429)高于对照组(0.926±0.263),差异有统计学意义(t=10.277,P<0.05)。lncRNA TINCR相对表达与HCC患者血管侵犯、肿瘤大小、肿瘤分期及血清AFP水平有关(t值分别为3.958、4.499、3.361、4.949,P值分别为<0.001、<0.001、0.001、<0.001)。HCC组患者血清IFNγ、IL-2水平明显低于对照组[(13.48±5.20)pg/ml vs(27.49±7.21)pg/ml、(21.89±6.45)pg/ml vs(32.05±7.89)pg/ml,t值分别为11.408、6.986,P值均<0.05],而IL-4、IL-10水平明显高于对照组[(13.73±3.35)pg/ml vs(9.36±2.73)pg/ml、(12.75±2.74)pg/ml vs(8.93±2.16)pg/ml,t值分别为6.426、6.909,P值均<0.05]。HCC患者外周血lncRNA TINCR相对表达量与血清IFNγ、IL-2水平呈负相关(r值分别为-3.164、-3.270,P值均<0.001),与患者血清IL-4、IL-10呈正相关(r值分别为2.963、3.044,P值分别为0.007、<0.001)。以lncRNA TINCR相对表达量≥1.700作为高表达,85例HCC患者中lncRNA TINCR高表达患者47例,低表达患者38例。log-rank检验结果显示,lncRNA TINCR低表达患者生存情况明显优于高表达患者(χ2=4.182,P<0.05)。结论HCC患者行TACE后外周血lncRNA TINCR表达明显高于健康人群,lncRNA TINCR表达与患者病理特征及Th1/Th2免疫平衡有密切联系,可作为患者生存预后的潜在预测指标之一。     

Cancer stem cell markers correlate with early recurrence and survival in hepatocellular carcinoma

AIM:To investigate whether expression of cancer stem cell(CSC)markers is associated with recurrence and survival in hepatocellular carcinoma(HCC)patients.METHODS:A consecutive series of 90 HCC patients who underwent curative hepatectomy between April2007 and April 2009 were analyzed.Of the 90 patients,38(42%)experienced recurrence within two years of surgery.To adjust for baseline differences between this early recurrence group and the other patients,propensity-score matching was used to generate 25 pairs of patients.Immunohistochemistry was used to compare expression of CD133,CD90,and epithelial cell adhesion molecule(EpCAM)in liver tissues from propensity score-matched patients and from 10 healthy adults.Associations of the three markers with HCC,clinicopathological characteristics,early recurrence,and survival time were explored.RESULTS:The expression of all three CSC markers was significantly higher in HCC tissue than in healthy liver tissue(P<0.001 for all).Among the HCC clinicopathology characteristics examined,the absence of tumor capsule was associated with CD133 expression(P=0.005);higher histopathology grade and larger tumor size were associated with CD90 expression(P=0.010 and 0.034,respectively);and elevated serum alpha-fetoprotein levels were associated with EpCAM expression(P=0.021).Expression of CD90 and EpCAM was significantly higher in the early recurrence group than in other patients(P=0.001 and 0.045,respectively),whereas CD133 expression was not significantly different between the two groups(P=0.440).Multivariate analysis identified only CD90 expression as significantly associated with early recurrence.Log-rank analysis identified expression of both CD90 and EpCAM as significantly associated with survival time of HCC patients.Cox regression identified EpCAM expression as an independent predictor of survival time.CONCLUSION:Expression of CD133,CD90,and EpCAM CSC markers may be linked to HCC tumor onset and/or progression.In addition,EpCAM expression is associated with shorter survival time,while CD90 expression is associated with early HCC recurrence.