p28GANK在胰腺导管癌中表达的临床意义

目的：探讨p28GANK在胰腺导管癌中表达及其临床意义。 方法：用免疫组化法检测p28GANK在48例胰腺导管癌及其癌旁组织中的表达,分析p28GANK胰腺导管癌中表达与患者临床病理因素及术后生存率的关系。 结果：p28GANK在胰腺导管癌组织中阳性表达率明显高于对应的癌旁组织（P<0.01）;p28GANK在胰腺导管癌组织中高表达与高TNM分期、低级别分化程度、转移有关（均P<0.05）,而与患者性别及年龄无关（均P>0.05）。p28GNAK阳性患者术后3年生存率明显低于阴性表达者（P=0.01）。 结论：p28GANK在胰腺导管癌中表达上调,其高表达与患者恶性进展程度密切相关。     

胰腺癌组织微血管密度及淋巴管密度的改变及临床意义

目的：研究胰腺癌组织中微皿管密度（MVD）和淋巴管密度（LVD）的变化、与胰腺癌临床病理的联系及相互关系。方法：采用免疫组织化学SABC法应用CD34检测41例胰腺导管腺癌患者配对癌组织和正常胰腺组织中MVD的表达情况,应用D2—40检测配对癌组织、癌旁组织及正常胰腺组织中LVD的表达情况,分析MVD和LVD与肿瘤分化程度、分期和淋巴转移间的相关性以及癌组织MVD与癌旁组织LVD表达之间的关系。结果：癌组织及正常胰腺组织MVD分别为46585±16,935和11．100±4．036,两组差异有统计学意义（P=0．000）。癌组织、癌旁及正常胰腺组织LVD分别为11．244±4．800、15．829±7．470和13．512±5．139;其中癌旁组织与正常胰腺组织LVD差异无统计学意义（P=0．060）,癌旁组织与癌组织的LVD差异有统计学意义（P=0．000）。胰腺癌组织MVD与癌旁组织LVD间存在相关性（P=0.025〈0．05）。结论：胰腺导管腺癌组织中MVD及LVD与肿瘤分化程度、病理分期及淋巴转移相关;胰腺癌组织内MVD与癌旁组织LVD间存在相关性。     

大肠癌组织中miRNA-21 表达水平及其与预后的研究

目的：探讨miRNA-21在大肠癌中的表达及其意义。 方法：检测90例大肠癌患者肿瘤组织以及癌旁组织中miRNA-21的表达水平,并对其表达水平与临床预后的关系进行分析。 结果：miRNA-21在肿瘤组织中表达量明显升高,（P<0.05）;miRNA-21在直径>6 cm的肿瘤中的表达水平显著高于<6 cm者;在>70岁的肿瘤患者中的表达水平明显高于<70岁者（P<0.05）。miRNA-21的高表达与生存期下降密切相关（HR=2.416, 95% CI：1.314~4.445, P=0.005）,而miRNA-21低表达的患者其生存期显著上升(HR=2.100, 95% CI：1.157~3.813, P=0.015),特别是TNM1期和2期的患者。 结论：检测miRNA-21的表达对大肠癌诊断及预后的判断有临床意义。     

PRDX1在人胰腺导管腺癌中的表达及其与病理指标的关系

目的 探讨过氧化还原蛋白1（peroxiredoxin 1,PRDX1）在胰腺导管腺癌（pancreatic ductal adenocarcinoma,PDAC）中的表达及与临床病理学参数的关系并评价其判断预后的价值。方法 采用免疫组织化学法分析117例PDAC组织石蜡切片及41例癌旁正常胰腺组织石蜡切片中的PRDX1表达,对PRDX1表达 水平与临床病理指标进行相关性分析,进行生存分析。采用Western blotting和实时定量PCR（qRT-PCR）检测9 对配对新鲜PDAC组织及癌旁正常胰腺组织中PRDX1蛋白质和mRNA水平的表达。结果 免疫组化显示PRDX1在PDAC中表达阳性率高于癌旁正常胰腺组织,差异有统计学意义（x2=9.761,P ＜0.01）;新鲜PDAC中PRDX1蛋白及mRNA表达明显高于配对的癌旁正常胰腺组织（t =9.187,P ＜0.01;t =7.829,P ＜0.011）;PRDX1表达与肿瘤直径、肿瘤TNM分期、淋巴结转移、病理分级有关（x2=8.876,P ＜0.01;x2=4.342,P ＜0.05;x2=9.273,P ＜0.01;x2=6.943,P ＜0.01）;PRDX1与术后复发率相关（x2=7.326,P ＜0.01）,PRDX1表达与生存期呈负相关（r =-0.845,P ＜0.05）。结论 PRDX1表达与PDAC的恶性程度有关,可作为判断PDAC预后的预 测因素。     

TRPM8在胰腺导管腺癌中的表达及意义

目的 检测TRPM8在胰腺导管腺癌中的表达情况并分析其临床意义.方法 收集我院肝胆外科自2008年至2010年40例行手术切除的胰腺导管腺癌病例的临床病理资料,分别采用实时荧光定量PCR（Real-Time PCR）、免疫组织化学和Western blotting的方法检测TRPM8 mRNA和蛋白水平的表达情况,并分析其与各临床病理参数之间的关系.结果 TRPM8在mRNA和蛋白水平表达一致.TRPM8mRNA在胰腺导管腺癌患者癌组织中表达明显高于正常组织[（0.0512±0.0498）vs （0.0008±0.0005）,P＜ 0.05].单因素和多因素分析发现TRPM8的表达是一个独立的预后因素.2年无病生存率和总生存率,TRPM8阳性染色组明显低于阴性染色组（48％ vs 18％,58％ vs 22％）,差异具有统计学意义（P＜ 0.05）.临床病理特征评估结果：TRPM8的高表达与胰腺导管腺癌组织的分化程度、TNM分期及淋巴结转移之间存在显著性相关（P＜0.05）,与肿瘤大小、患者年龄、性别等无关.结论 TRPM8在胰腺导管腺癌中表达上调并与一些临床病理特征密切相关,提示TRPM8可能是反映胰腺导管腺癌发生发展、侵袭、转移及预后的重要生物学指标.     

核基质结合蛋白1在胰腺导管腺癌中的表达及意义

目的 探讨胰腺导管腺癌(PDAC)中核基质结合蛋白1(SATB1)的mRNA和蛋白表达水平及其与临床病理特征的关系,评价SATB1在PDAC预后判断中的价值.方法 应用免疫组织化学法检测49例PDAC组织及配对的癌旁组织石蜡标本SATB1蛋白表达水平,利用Western blot 和反转录-聚合酶链反应(RT-PCR)检测16对配对冷冻保存的新鲜PDAC组织、癌旁组织中SATB1蛋白和mRNA表达水平.结果 免疫组织化学结果显示,SATB1在13例PDAC中呈高表达,癌旁组织有5例高表达(26.5％比10.2％).SATB1的表达与PDAC分化程度(x2=4.131,P＜0.05)、淋巴结转移(x2 =5.000,P＜0.05)、T分期(x2=14.348,P＜0.05)和TNM分期(x2=6.69,P＜0.05)相关.阳性表达SATB1的PDAC患者术后中位生存时间为353 d,阴性表达SATB1者为508 d.RT-PCR和Western blot结果显示SATB1在PDAC患者中mRNA表达高于癌旁组织(t=2.432,P＜0.05),蛋白表达水平差异无统计学意义(t=0.324,P＞0.05).结论 SATB1在PDAC中表达呈上调状态,与PDAC临床病理因素及预后相关.     

胃癌外周血TWA1 mRNA的表达与预后价值

目的检测胃癌（GC）患者外周血TWA1 mRNA表达水平，分析其与患者长期预后的关系。 方法选择2016年6月至2017年6月于西宁市第二人民医院诊治的97例GC患者，实时荧光定量PCR（RT-PCR）检测外周血TWA1表达量，随访并记录患者无进展生存期（PFS）。受试者工作特征（ROC）曲线判定TWA1 mRNA的阈值，分组比较TWA1 mRNA不同表达患者的PFS情况。Cox回归模型评估TWA1 mRNA水平对GC患者预后的预测价值。 结果随访（20.91±5.76）个月，随访率为94.79%（91/94），平均PFS（21.83±5.13）个月。TWA1 mRNA对GC患者PFS判定的曲线下面积为0.781（95% CI：0.687~0.875，P<0.001），截断值为1.27。TWA1 mRNA高表达患者的PFS显著短于低表达患者（χ²=14.415，P<0.01）。淋巴结转移（HR=3.328，95% CI：2.098~5.971，P=0.044）、TNM Ⅲ~Ⅳ期（HR=3.400，95% CI：1.114~4.795，P=0.011）及外周血TWA1 mRNA高表达（HR=7.429，95% CI：1.711~32.263，P=0.007）是影响患者PFS的独立危险因素。 结论外周血TWA1的表达与GC患者PFS显著相关，TWA1 mRNA水平对GC患者随访预后情况具有较好的预测价值。     

Grb2在胰腺癌中的表达及其意义

目的：探讨生长因子受体结合蛋白2（Grb2）在胰腺癌中的表达及其意义。 方法：分别采用real-time PCR和Western blot方法检测6种胰腺癌细胞株中Grb2基因和蛋白表达水平;采用组织芯片检测80例胰腺癌组织及癌旁胰腺组织中Grb2的表达情况,并分析Grb2表达状态与胰腺癌患者临床病理特征的关系。 结果：Grb2的mRNA与蛋白在高侵袭力、低分化细胞株PANC-1、MIA-PaCa-2、AsPC-1中呈相对高表达,而在低侵袭力、高分化细胞株BxPC-3、SW1990、capan-2中呈相对低表达;Grb2在胰腺癌组织中均有表达,而在癌旁胰腺组织中不表达或低表达,统计分析显示,Grb2的高表达与肿瘤低分化以及淋巴结或者远处转移有关（均P<0.05）。 结论：Grb2的表达与胰腺癌的分化程度和侵袭转移力密切相关,高表达者肿瘤恶性程度高,预后差。     

Hedgehog信号通路转录因子Gli2表达对肝癌进展和生存预后的影响

目的探讨Hedgehog（Hh）信号通路转录因子Gli2在肝癌中的表达及其与预后的关系。 方法选取68例肝癌及20例肝血管瘤旁肝组织切除标本,采用免疫组织化学法检测Gli2蛋白表达,并分析Gli2表达与肝癌临床病理特征及预后的关系。 结果Gli2蛋白在肝癌组织中的表达率（63.2%）高于癌旁组织（11.8%）及正常肝组织（10.0%）(χ²=38.431、17528,均P<0.01);Gli2表达水平与肝癌分化程度、包膜是否完整、有无血管侵犯、早期复发及肝内转移相关（P<0.05）;Gli2蛋白高表达患者术后总生存率和无瘤生存率明显低于低表达者（P<0.05）;多因素分析表明,Gli2蛋白表达水平是影响肝癌患者术后总生存率及无瘤生存率的独立预后因素（HR=2.239,P<0.05;HR=1.917,P<0.05）。 结论Gli2的高表达与肝癌的侵袭转移特性相关,可作为评价肝癌患者术后预后的标志物之一。     

Runt相关转录因子2在人肾透明细胞癌组织的表达及其临床意义

目的探讨Runt相关转录因子2(RUNX2)在肾透明细胞癌(ccRCC)中的表达及其与患者预后和临床病理特征之间的关系。方法基于肾癌肿瘤基因组图谱(TCGA)数据, 分析RUNX2在癌和癌旁组织中的表达及其预后价值。采用多色免疫荧光标记(mIHC)技术分析RUNX2在癌和癌旁组织中的分布特征, 并结合临床资料进行χ2检验。单因素和拟合多因素Cox模型分析RUNX2及其他指标的预后价值。基于TCGA数据库, 探讨RUNX2与免疫细胞浸润的相关性。结果 TCGA数据分析结果显示, RUNX2在癌组织中的表达显著高于正常组织(P<0.001)。mIHC结果表明RUNX2在癌组织表达水平高于癌旁组织(Z=-2.123, P<0.05), 且其表达水平与患者总生存期呈负相关[P<0.01, 风险比(HR)=2.768, 95%可信区间(CI):1.120～6.838]。RUNX2表达水平与患者美国癌症联合委员会(AJCC)临床分期明显相关(χ2=4.505, P<0.05)。多因素Cox回归模型显示年龄(P<0.01, HR=1.068, 95%CI:1.024～1...     

Results of pancreaticoduodenectomy for pancreatic cancer: extended versus standard procedure

In Western experience, the long-term survival benefit after extended pancreaticoduodenectomy (EPD) in patients with pancreatic ductal adenocarcinoma is still controversial. The aim of this work was to evaluate weather EPD for pancreatic ductal adenocarcinoma prolongs long-term survival compared to standard pancreaticoduodenectomy (SPD). From November 1992 to September 1996, we performed pancreatic resections in 30 patients affected by stage I-III pancreatic ductal adenocarcinoma: 13 patients underwent SPD and 17 patients underwent EPD, consecutively. The two groups of patients were similar for all the demographic, clinical, and pathological characteristics, and all the intraoperative factors considered except the number of resected lymph nodes (mean number per case = 34.2 +/- 15.5 in the EPD group versus 12.8 +/- 3.6 in the SPD group, p <0.001) and the operative time (median time per case = 375 minutes in the EPD group versus 270 minutes in the SPD group, p = 0.009). Patients in the two groups experienced a similar postoperative course. The estimated survival probability at 1 and 3 years after operation was 0.76 (95% confidence interval [CI]: 0.49 to 0.90) and 0.24 (95% CI: 0.07 to 0.45) in the EPD group; 0.31 (95% CI: 0.09 to 0.55) and 0.08 (95% CI: 0.00 to 0.29) in the SPD group (p = 0.014). According to a Cox model, the treatment was associated with R0 patients' long-term survival (SPD versus EPD: hazard ratio (HR) = 4.82, 95% CI: 1.66 to 14.00, p = 0.004). Grading of tumor differentiation was confirmed to be a relevant prognostic factor (poor versus moderate: HR = 4.33, 95% CI: 1.49 to 12.61, p = 0.007), whereas type of resection had no significant effect (pylorus-preserving versus hemigastrectomy: HR = 1.49, 95% CI: 0.56 to 3.95, p = 0.42). The proportion of R0 patients with local recurrence was lower in the EPD group (20.0% versus 70.0%, p = 0.034).     

Krüppel 样转录因子 9 在胰腺癌中的表达及其临床意义

目的:探讨Krüppel样转录因子9(KLF9)在胰腺癌中的表达并探讨其与胰腺癌患者临床病理参数、预后的关系。方法:收集200例配对的胰腺癌组织与癌旁组织标本,分别用RT-PCR(28对)、Westernblot(4对)和免疫组化(全部标本)检测KLF9的表达,分析KLF9的表达水平与患者临床病理参数以及生存率的关系。结果:RT-PCR结果显示,在28例配对标本中,21例(75%)胰腺癌组织中KLF9m RNA的表达水平明显低于其癌旁正常胰腺组织。Westernblot结果显示,与癌旁正常胰腺组织比较,胰腺癌组织中KLF9蛋白表达水平明显下调。免疫组化显示,在胰腺癌组织中KLF9的染色强度明显减弱。与患者临床病理参数关系分析结果显示,KLF9的表达水平与肿瘤的分化程度(P=0.008)和血管侵犯(P=0.006)有关。生存分析显示,KLF9阳性表达患者1、2、3年总生存率明显高KLF9阴性表达患者(41%、31%、16%vs.18%、6%、6%)、中位生存时间明显长于KLF9阴性表达患者(21.05个月vs.11.82个月)(均P0.05)。结论:KLF9在胰腺癌中表达下调,且可能与不良预后密切相关。     

KIF4A在肝细胞癌中的表达及预后价值分析

背景与目的:肝细胞癌(HCC)是原发性肝癌最常见的病理类型,其起病隐匿,预后较差,位居癌症相关死亡原因第3位.KIF4A在多种恶性肿瘤中呈高表达且与不良预后密切相关,然而其在HCC中的作用及机制尚不清楚.因此,本研究分析KIF4A基因在HCC中的表达情况及预后价值,并探讨相关的分子机制.方法:从癌症基因组图谱(TCGA...     

Preoperative Platelet Count and Survival Prognosis in Resected Pancreatic Ductal Adenocarcinoma

BACKGROUND: High platelet counts are associated with an adverse effect on survival in various neoplastic entities. The prognostic relevance of preoperative platelet count in pancreatic cancer has not been clarified. METHODS: We performed a retrospective review of 205 patients with ductal adenocarcinoma who underwent surgical resection between 1990 and 2003. Demographic, surgical, and clinicopathologic variables were collected. A cutoff of 300,000/mul was used to define high platelet count. RESULTS: Of the 205 patients, 56 (27.4%) had a high platelet count, whereas 149 patients (72.6%) comprised the low platelet group. The overall median survival was 17 (2-178) months. The median survival of the high platelet group was 18 (2-137) months, and that of the low platelet group was 15 (2-178) months (p = 0.7). On multivariate analysis, lymph node metastasis, vascular invasion, positive margins, and CA 19-9 > 200 U/ml were all significantly associated with poor survival. CONCLUSIONS: There is no evidence to support preoperative platelet count as either an adverse or favorable prognostic factor in pancreatic ductal adenocarcinoma. Use of 5-year actual survival data confirms that lymph node metastases, positive margins, vascular invasion, and CA 19-9 are predictors of poor survival in resected pancreatic cancer.     

Tumor angiogenesis as a prognostic predictor in pancreatic cancer

The purpose of this study was to evaluate the role of angiogenesis, proliferative activity (assessed by Ki-67 expression), p53 and ras-oncogene (H-ras) expression, and conventional clinicopathologic factors in predicting overall survival rates in patients with pancreatic ductal adenocarcinoma. We followed-up 22 patients with ductal adenocarcinoma of the pancreas for a median of 19 months (range, 2 to 44 months). Angiogenesis was quantitated as vascular surface density (VSD) and the number of vessels per mm² stroma (NVES) after microvessels were immunostained, using factor VIII-related antigen. p53, H-ras, and Ki-67 proteins were also determined immunohistochemically. VSD and NVES showed significant correlations with increased proliferative activity, poor tumor differentiation, and tumor size of 3 cm or more (P = 0.001, P = 0.013, and P = 0.047, respectively). The overall 2-year survival rate of 33.3% in patients with high VSD and NVES values was significantly worse than that of 66.6% estimated in patients with low microvessel count (log rank, 3.97; P = 0.046). In multivariate analysis using the Cox model, VSD was found to be an independent prognostic factor of survival (P = 0.039). H-ras and p53 expressions were not correlated with angiogenesis parameters. We conclude that, in pancreatic ductal adenocarcinoma, angiogenesis is closely related to tumor growth and patient survival. Received: April 11, 2000 / Accepted: June 16, 2000     

Expression of glial cell line-derived neurotrophic factor family members and their receptors in pancreatic cancers

BACKGROUND: The glial cell line-derived neurotrophic factor (GDNF) is a member of neurotrophic polypeptide family, which promotes survival and rescue of various neural cells in the central and peripheral nerve systems. We previously reported that GDNF promotes tumor cell invasion in pancreatic cancer cell lines. The purpose of this study was to investigate GDNF family expression and the status of related receptors in actual cancer tissues, and assess correlations with clinicopathologic behavior. METHODS: Immunohistochemical assessment of GDNF, neurturin, persephin, artemin, GDNF family receptor alpha-1 and alpha-2, and RET was performed for 51 cases of surgically resected pancreatic cancer. RESULTS: In all intrapancreatic nerves, GDNF and artermin were expressed strongly. In pancreatic cancer tissues. The expression of RET was stronger than that seen in normal ductal cells and was significantly related to the survival rate after resection (P = .026) and lymphatic invasion (P = .014). Intrapancreatic neural invasion was significantly related to the expression of GDNF (P = .047). CONCLUSIONS: We conclude that the expression of RET in pancreatic cancer tissues may be a useful prognostic marker and GDNF may play an important role in neural invasion.     

Survivin expression is a prognostic marker in pancreatic cancer patients

BACKGROUND: In this study, we assessed survivin expression in pancreatic cancer specimens from patients who underwent either pancreatic resection alone or pancreatic resection plus postoperative radiation therapy (PORT) to evaluate whether survivin expression is predictive of sensitivity to PORT and outcome in pancreatic cancer patients. METHODS: Fifty-two patients who underwent pancreatic resection for ductal adenocarcinomas were included in this study. Forty-seven pancreatic ductal adenocarcinoma and 5 normal pancreatic tissues were evaluated for survivin expression by immunohistochemistry. Then the relationship between survivin expression and clinicopathologic data were analyzed. RESULTS: Sixty-eight percent (32/47) of pancreatic cancer tissues were positive for survivin expression; 32% (15/47) were negative. Normal pancreatic exocrine tissues were negative for survivin expression (0/5). Survival of the patients with positive survivin was significantly shorter than those with negative survivin (P = .02). Survivin was an independent variable that correlated with overall survival (P = .01). There was no difference in survival time between patients with and without PORT. Likely, PORT showed no impact on survival time in survivin-positive patients (P = .12) as well as in survivin-negative patients (P = .95). CONCLUSIONS: The results suggest that survivin expression in pancreatic cancer tissues could be a useful prognostic marker in pancreatic cancer patients.     

Prognostic Implications of Netrin-1 Expression and Its Receptors in Patients with Adenocarcinoma of the Pancreas

Background To assess the interaction between the expression of netrin-1 or of its receptors to the prognosis of ductal adenocarcinoma of the pancreas. Methods In 82 patients with resectable pancreatic adenocarcinoma who underwent curative operation, the expression patterns of netrin-1, deleted in colorectal carcinomas (DCC), UNC5H3, and neogenin were determined by immunohistochemical staining. Kaplan-Meier analysis was performed to assess the prognostic relevance of the examined expression patterns. Results Median follow-up was 15 ± 19.9 months (range, 4–108 months). Patients suffering from tumors with no or little expression of netrin-1 (n = 67) had a median recurrence-free survival of 10 months (95% CI, 7–13 months), while a middle to strong expression (n = 15) was associated with a significantly worse median recurrence-free survival of only four months (95% CI, three to five months, p = 0.0165). Overall and recurrence-free survival showed no significant differences between the different expression patterns of DCC, UNC5H3 or neogenin. Netrin-1 expression had significant impact (p = 0.001) on overall survival of patients suffering from poorly differentiated tumors. Stratification according to the nodal status revealed significant influence (p = 0.007) of UNC5H3 expression on the overall survival of patients with pN1 status. Conclusion Expression of netrin-1 has significant impact on time to tumor relapse in adenocarcinoma of the pancreas. Netrin-1 expression is associated with worse outcome in poorly differentiated pancreatic adenocarcinomas. Risk-stratification according to the UNC5H3 receptor expression pattern shows that node positive patients (pN1) with no to little UNC5H3 expression carry a significantly worse prognosis than those with middle to strong UNC5H3 expression.