乳腺癌中丝／苏氨酸蛋白激酶Plk1mRNA的表达及其预后价值

目的：检测乳腺癌细胞和组织中丝／苏氨酸蛋白激酶Plk1基因mRNA的表达情况并分析其预后价值。方法：应用半定量RT-PCR方法分析3株人乳腺癌细胞和1株正常乳腺上皮细胞中Plk1基因mRNA的表达水平。同时分析84例乳腺癌及对应的癌旁正常乳腺上皮组织中Plk1mRNA的表达水平。统计学分析Plk1mRNA表达水平与乳腺癌患者年龄、肿瘤大小、组织分化程度、淋巴结转移状况、TNM分期和雌激素受体（ER）等临床病理参数之间的关系,以及与预后之间的关系。结果：Plk1基因mRNA在乳腺癌细胞中的相对表达水平显著高于其在正常乳腺上皮细胞中的相对表达水平（P值均小于〈0．05）。另外,Plk1mRNA在乳腺癌组织中平均表达水平（0．88±0．18）显著高于其在癌旁正常乳腺上皮组织中平均表达水平（0．22±0．10;P〈0．01）。统计学分析结果袁明：Plk1mRNA表达水平和乳腺癌患者的淋巴结转移状况及TNM分期密切相关（P=0．009或0．007）。Kaplan—Meier生存曲线分析结果表明：高Plk1mRNA表达水平的乳腺癌患者的5年无疾病进展率及总体生存率均显著低于低Plk1mRNA表达水平的乳腺癌患者（P=0．0026及0．0136）。COX模型的多因素预后分析结果表明：Plk1基因mRNA表达水平是乳腺癌患者的一个独立的预后因素（HR=4．764,95％CI：1．341-6．123,P=0．0025）。结论：Plk1在乳腺癌组织呈现高表达水平,其mRNA表达水平有望成为临床乳腺癌患者一个重要的预后判断分子指标。     

乳腺癌中丝/ 苏氨酸蛋白激酶Plk1 mRNA 的表达及其预后价值

目的:检测乳腺癌细胞和组织中丝/苏氨酸蛋白激酶Plk1基因mRNA的表达情况并分析其预后价值。方法:应用半定量RT-PCR方法分析3株人乳腺癌细胞和1株正常乳腺上皮细胞中Plk1基因mRNA的表达水平。同时分析84例乳腺癌及对应的癌旁正常乳腺上皮组织中Plk1 mRNA的表达水平。统计学分析Plk1 mRNA表达水平与乳腺癌患者年龄、肿瘤大小、组织分化程度、淋巴结转移状况、TNM分期和雌激素受体(ER)等临床病理参数之间的关系,以及与预后之间的关系。结果:Plk1基因mRNA在乳腺癌细胞中的相对表达水平显著高于其在正常乳腺上皮细胞中的相对表达水平(P值均小于<0.05)。另外,Plk1 mRNA在乳腺癌组织中平均表达水平(0.88±0.18)显著高于其在癌旁正常乳腺上皮组织中平均表达水平(0.22±0.10;P<0.01)。统计学分析结果表明:Plk1 mRNA表达水平和乳腺癌患者的淋巴结转移状况及TNM分期密切相关(P=0.009或0.007)。Kaplan-Meier生存曲线分析结果表明:高Plk1 mRNA表达水平的乳腺癌患者的5年无疾病进展率及总体生存率均显著低于低Plk1 mRNA表达水平的乳腺癌患者(P=0.0026及0.0136)。COX模型的多因素预后分析结果表明:Plk1基因mRNA表达水平是乳腺癌患者的一个独立的预后因素(HR=4.764,95%CI:1.341~6.123,P=0.0025)。结论:Plk1在乳腺癌组织呈现高表达水平,其mRNA表达水平有望成为临床乳腺癌患者一个重要的预后判断分子指标。     

The Prognostic Value of BRCA1 mRNA Expression Levels Following Neoadjuvant Chemotherapy in Breast Cancer

Background

A fraction of sporadic breast cancers has low BRCA1 expression. BRCA1 mutation carriers are more likely to achieve a pathological complete response with DNA-damage-based chemotherapy compared to non-mutation carriers. Furthermore, sporadic ovarian cancer patients with low levels of BRCA1 mRNA have longer survival following platinum-based chemotherapy than patients with high levels of BRCA1 mRNA.

Methodology/Principal Findings

Tumor biopsies were obtained from 86 breast cancer patients who were candidates for neoadjuvant chemotherapy, treated with four cycles of neoadjuvant fluorouracil, epirubicin and cyclophosphamide. Estrogen receptor (ER), progesterone receptor (PR), HER2, cytokeratin 5/6 and vimentin were examined by tissue microarray. HER2 were also assessed by chromogenic in situ hybridization, and BRCA1 mRNA was analyzed in a subset of 41 patients for whom sufficient tumor tissue was available by real-time quantitative PCR. Median time to progression was 42 months and overall survival was 55 months. In the multivariate analysis for time to progression and overall survival for 41 patients in whom BRCA1 could be assessed, low levels of BRCA1 mRNA, positive PR and negative lymph node involvement predicted a significantly lower risk of relapse, low levels of BRCA1 mRNA and positive PR were the only variables associated with significantly longer survival.

Conclusions/Significance

We provide evidence for a major role for BRCA1 mRNA expression as a marker of time to progression and overall survival in sporadic breast cancers treated with anthracycline-based chemotherapy. These findings can be useful for customizing chemotherapy.     

Role of Y-Box Binding Proteins in Ontogenesis

Biochemistry (Moscow) - Y-box binding proteins (YB proteins) are multifunctional DNA/RNA-binding proteins capable of regulating gene expression at multiple levels. At present, the most studied...     

Prognostic Value of Cancer Stem Cell Marker ALDH1 Expression in Colorectal Cancer: A Systematic Review and Meta-Analysis

Objective

Many studies have indicated the prognostic and clinicopathological value of aldehyde dehydrogenase 1 (ALDH1) in colorectal cancer (CRC) patients still remains controversial. Thus we performed this study to clarify the relationship between high ALDH1 expression in CRC and its impact on survival and clinicopathological features.

Methods

Publications for relevant studies in Pubmed, the Cochrane Library, Embase, and China National Knowledge Infrastructure (CNKI) through April 2015 were identified. Only articles describing ALDH1 antigen with immunohistochemistry in CRC were included. The software RevMan 5.1 was used to analyze the outcomes, including 5-year overall survival (OS), disease-free survival (DFS) and clinicopathological features.

Results

9 studies with 1203 patients satisfying the criteria were included. The overall rate of high ALDH1 expression was 46.5% by immunohistochemical staining. High ALDH1 expression as an independent prognostic factor was significantly associated with the 5-year OS and DFS (OR = 0.42, 95%CI: 0.26–0.68, P = 0.0004; OR = 0.38, 95%CI: 0.24–0.59, P < 0.0001, respectively). High ALDH1 expression was highly correlated with the tumor (T) stage (T3 + T4 vs. T1 + T2; OR = 2.16, 95%CI: 1.09–4.28, P = 0.03), lymph node (N) stage (N1 + N2 vs. N0; OR = 1.8; 95%CI: 1.17–2.79, P = 0.008), and tumor differentiation (G3 vs. G1 + G2; OR = 1.88; 95%CI: 1.07–3.30, P = 0.03). However, high ALDH1 expression was not significantly correlated with the patient age (>60 years old vs. <60 years old; OR = 1.11, 95%CI: 0.63–1.94, P = 0.72).

Conclusions

High ALDH1 expression indicates a poor prognosis in CRC patients. Moreover, high ALDH1 expression correlates with the T stage, N stage, and tumor differentiation, but not with age.     

Prognostic Value of Mitotic Index and Bcl2 Expression in Male Breast Cancer

The incidence of male breast cancer (MBC) is rising. Current treatment regimens for MBC are extrapolated from female breast cancer (FBC), based on the assumption that FBC prognostic features and therapeutic targets can be extrapolated to MBC. However, there is yet little evidence that prognostic features that have been developed and established in FBC are applicable to MBC as well. In a recent study on FBC, a combination of mitotic index and Bcl2 expression proved to be of strong prognostic value. Previous papers on Bcl2 expression in MBC were equivocal, and the prognostic value of Bcl2 combined with mitotic index has not been studied in MBC. The aim of the present study was therefore to investigate the prognostic value of Bcl2 in combination with mitotic index in MBC. Immunohistochemical staining for Bcl2 was performed on tissue microarrays of a total of 151 male breast cancer cases. Mitotic index was scored. The prognostic value of Bcl2 expression and Bcl2/mitotic index combinations was evaluated studying their correlations with clinicopathologic features and their prediction of survival. The vast majority of MBC (94%) showed Bcl2 expression, more frequently than previously described for FBC. Bcl2 expression had no significant associations with clinicopathologic features such as tumor size, mitotic count and grade. In univariate survival analysis, Bcl2 had no prognostic value, and showed no additional prognostic value to tumor size and histological grade in Cox regression. In addition, the Bcl2/mitotic index combination as opposed to FBC did not predict survival in MBC. In conclusion, Bcl2 expression is common in MBC, but is not associated with major clinicopathologic features and, in contrast to FBC, does not seem to have prognostic value, also when combined with mitotic index.     

HEPIS的表达谱及其在直肠癌中的表达分析

HEPIS是一个新基因,关于HEPIS的表达和功能尚不十分清楚.本研究首先构建了HEPIS的表达载体pEGFP-C3-HEPIS,采用双荧光素酶报告实验检测了 HEPIS对Wnt、CRE、NF-KB和HRE信号通路的作用,随后采用RNA原位杂交(RISH)检测了 HEPIS在12种不同器官(乳腺,结肠,食道,肾,肝,肺,卵巢,胰腺,前列腺,直肠,胃和宫颈)的癌组织和正常组织的表达差异,并且检测了 HEPIS在40例直肠腺癌和直肠正常组织的表达.研究表明,在293T细胞转染pEGFP-C3-HEPIS后,无论是转录水平还是翻译水平,HEPIS均显著增加,且HEPIS可以显著抑制Wnt、CRE和NF-KB 3条信号通路,对NF-κB信号通路的抑制最为显著.RNA原位杂交实验证实HEPIS在12个器官的癌组织和正常组织中表达存在明显的表达差异.采用GEPIA对HEPIS在直肠癌及正常组织的表达差异进行了分析,结果表明HEPIS在正常直肠组织高表达,进一步采用RISH分析了 HEPIS在40例直肠癌和癌旁组织的表达差异,分析表明HEPIS在正常直肠组织的表达显著高于癌组织(P＜0.01),与GEPIA分析结果一致,说明HEPIS可能是直肠癌的一个潜在抑癌基因.     

The Prognostic Value of SOX2 Expression in Non-Small Cell Lung Cancer: A Meta-Analysis

Objective

To investigate the association of SOX2 expression in tumor with clinicopathological features and survival of non-small-cell lung carcinoma (NSCLC) patients.

Methods

Publications assessing the clinicopathological characteristics and prognostic significance of SOX2 in NSCLC were identified up to May 2013. A meta-analysis of eligible studies was performed using standard statistical methods to clarify the association between SOX2 expression and these clinical parameters.

Results

A total of eight studies met the inclusion criteria. Analysis of these data showed that SOX2 expression was positively associated with squamous histology, (pooled OR = 5.26, 95% CI: 1.08–25.6, P = 0.040). Simultaneously, we also found that SOX2 expression was positively associated with overall survival (pooled HR = 0.65, 95% CI: 0.47–0.89, P = 0.007, random-effect).

Conclusions

SOX2 expression in tumor is a candidate positive prognostic biomarker for NSCLC patients.     

The Prognostic Value of Phosphorylated AKT Expression in Non-Small Cell Lung Cancer: A Meta-Analysis

Objectives

Phosphorylated AKT (p-AKT), constitutive activation of AKT, is a potentially interesting prognostic marker and therapeutic target in non-small cell lung cancer (NSCLC). However, the available results of p-AKT expression in NSCLC are heterogeneous. Therefore, a meta-analysis of published researches investigating the prognostic relevance of p-AKT expression in patients with NSCLC was performed.

Materials and Methods

A literature search via PubMed, EMBASE and CNKI (China National Knowledge Infrastructure) databases was conducted. Data from eligible studies were extracted and included into meta-analysis using a random effects model.

Results

A total of 1049 patients from nine studies were included in the meta-analysis. Nine studies investigated the relationship between p-AKT expression and overall survival using univariate analysis, and five of these undertook multivariate analysis. The pooled hazard ratio (HR) for overall survival was 1.49 (95% confidence interval (CI): 1.01-2.20) by univariate analysis and 1.02 (95% CI: 0.54-1.95) by multivariate analysis.

Conclusion

Our study shows that positive expression of p-AKT is associated with poor prognosis in patients with NSCLC. However, adequately designed prospective studies need to perform.     

Prognostic Implications of SLIT and ROBO1 Expression in Gallbladder Cancer

SLIT, a secretory glycoprotein, and its receptor roundabout (ROBO) are expressed in several types of cancer and have been implicated in tumor angiogenesis. The purpose of this study was to determine the prognostic implications of SLIT and ROBO1 expression and their association with clinicopathologic characteristics in gallbladder cancer. A retrospective analysis of 109 consecutive patients who underwent primary gallbladder cancer resection was conducted. Univariate and multivariate models were used to analyze the effect of clinicopathologic factors on survival. Expression of SLIT and ROBO1 was evaluated by immunohistochemistry, and their association with clinicopathologic characteristics was analyzed using mean testing. Multivariate linear regression analysis was also applied to investigate the independent predictors of ROBO1 expression. Seventy-five patients were included in the post-resection survival analysis, with 1-year and 3-year overall survival rates of 60 and 40 %, respectively. Univariate analysis revealed that pN classification, pT classification, pM classification, liver involvement, perineural invasion, TNM staging, Nevin staging, and microscopic resection margins affect prognosis. Multivariate analysis confirmed that pN classification, liver involvement, and perineural invasion are independent prognostic factors. In the mean tests of 109 cases, the mean difference of SLIT immunoreactivity was significant according to the presence of gallstones (P = 0.003) and liver involvement (P = 0.005), while the mean difference of ROBO1 immunoreactivity was significant according to liver involvement (P < 0.001), TNM staging (P < 0.001), and Nevin staging (P < 0.001). Multivariate analysis of ROBO1 immunoreactivity showed that SLIT immunoreactivity and TNM stage (adjusted R ² = 0.203) or SLIT immunoreactivity and Nevin stage (adjusted R ² = 0.195) were independent predictors of ROBO1 expression. pN classification, liver involvement, perineural invasion, and pathologic stage are significant prognostic factors for gallbladder cancer survival. SLIT expression is associated with cholelithiasis and liver involvement, and ROBO1 expression is associated with liver involvement and pathologic stage. In addition, SLIT expression and pathologic stage predict ROBO1 expression independently.     

直肠癌组织中PTEN和Notch1的表达及其与临床病理参数的关系

目的:探究直肠癌组织中PTEN和Notch1的表达及其与临床病理参数的关系。方法:收集2014年1月~2015年4月,我院肿瘤外科确诊48例直肠癌病理组织标本与20例直肠癌患者癌旁正常组织标本为研究对象,应用免疫组化链霉菌抗生物素蛋白-过氧化物酶连结法(S-P法)分析PTEN和Notch1蛋白在直肠癌病理组织和正常组织中的表达情况。结果:PTEN和Notch1主要表达于直肠癌组织细胞质中,呈现棕黄色;Notch1在直肠癌病理组织中表达率显著高于正常组织(P0.05);PTEN在正常组织表达率显著高于在直肠癌组织(P0.05);Notch1在淋巴转移、中底分化及分期为C期患者病理组织中表达率较高(P0.05);PTEN在无淋巴转移、中底分化程度及A+B期患者病理组织表达率较高(P0.05);相关性分析显示,Notch1和PTEN在直肠癌病理组织中表达呈现负相关关系(r=-0.534,P=0.000)。结论:Notch1和PTEN表达失调在直肠癌的发生、发展和淋巴结转移中有重要作用;PTEN表达可能对直肠癌的发生、发展具有抑制作用,Notch1表达可能对直肠癌的发生、发展具有促进作用。     

Prognostic Value and Clinicopathology Significance of MicroRNA-200c Expression in Cancer: A Meta-Analysis

MiR-200c has been shown to be related to cancer formation and progression. However, the prognostic and clinicopathologic significance of miR-200c expression in cancer remain inconclusive. We carried out this systematic review and meta-analysis to investigate the prognostic value of miR-200c expression in cancer. Pooled hazard ratios (HRs) of miR-200c for overall survival (OS) and progression-free survival (PFS) were calculated to measure the effective value of miR-200c expression on prognosis. The association between miR-200c expression and clinical significance was measured by odds ratios (ORs). Twenty-three studies were included in our meta-analysis. We found that miR-200c was not significantly correlated with OS (HR = 1.41, 95%Cl: 0.95-2.10; P = 0.09) and PFS (HR = 1.12, 95%Cl: 0.68-1.84; P = 0.67) in cancer. In our subgroup analysis, higher expression of miR-200c was significantly associated with poor OS in blood (HR = 2.10, 95%CI: 1.52-2.90, P<0.00001). Moreover, in clinicopathology analysis, miR-200c expression in blood was significantly associated with TNM stage, lymph node metastasis and distant metastasis. MiR-200c may have the potential to become a new blood biomarker to monitor cancer prognosis and progression.     

MRI在直肠癌术前N分期中的应用价值研究

目的：分析直肠癌直肠系膜内淋巴结的MRJ表现,评价MRI在直肠癌术前N分期中的应用价值。方法：对2011年8月至2012年2月经手术治疗并经病理证实的116例直肠癌病例行术前MRI检查,观察和记录每个淋巴结的大小、边缘以及信号,以病理学诊断转移淋巴结阳性为标准进行分组,由2位影像科医生采用双盲法阅片并达成一致。结果：MRI诊断直肠周围淋巴结转移的各项诊断标准具有统计学意义,其中淋巴结短轴直径与转移相关性的统计结果为（P〈0．05,r=0．210）,淋巴结边缘与转移相关性的统计结果为（P〈0．05,r=0．180）,淋巴结信号与转移相关性的统计结果为（P〈0．05,r=0．209）。Logistic回归分析显示淋巴结大小诊断淋巴结转移的可信度最高,Wals值为13．180。结论：综合分析直肠周围淋巴结大小,边缘、信号对诊断淋巴结转移有较大作用,其中以淋巴结大小的作用最为显著。     

The Prognostic Value of Forkhead Box P3 Expression in Operable Breast Cancer: A Large-Scale Meta-Analysis

Background

Recent studies have shown that the forkhead box P3 (FOXP3) protein has a prognostic role in breast cancer. However, these results are controversial. Therefore, the aim of this meta-analysis was to clarify the prognostic role of FOXP3 expression in operable breast cancer cases.

Methods

Eligible studies describing the use of FOXP3 as a prognostic factor for operable breast cancer cases were identified. Clinicopathological features, disease-free survival (DFS), and overall survival (OS) data were collected from these studies and were analyzed using Stata software.

Results

A total of 16 articles containing data from 13,217 breast cancer patients met the inclusion criteria established for this study. The subsequent meta-analysis that was performed showed that high levels of FOXP3 are not significantly associated with DFS and OS with significant heterogeneity. An additional subgroup analysis demonstrated that intratumoral FOXP3+ regulatory T cells (Tregs) were positively correlated with adverse clinicopathological parameters, yet they did not show an association with DFS or OS. For tumor cells, the pooled results revealed that FOXP3 is significantly associated with DFS (HR: 2.55, 95% CI: 1.23–5.30) but is not associated with clinicopathological parameters or OS. We also observed a significant correlation between FOXP3 expression and survival in the estrogen receptor-positive (ER)+ subgroup (HR: 1.83, 95% CI: 1.36–2.47 for DFS, HR: 1.87, 95% CI 1.28–2.73 for OS), in the Asian region (HR: 1.98, 95% CI: 1.56–2.50 for DFS, HR: 1.93, 95% CI: 1.12–3.35 for OS) and using the median as the FOXP3-positive cut-off value (HR: 1.94, 95% CI: 1.57–2.39 for DFS, HR: 2.06; 95% CI: 1.36–3.11 for OS).

Conclusion

This meta-analysis indicates that a prognostic role for FOXP3 expression in operable breast cancer cases depends on the FOXP3-positive region, ER status, geographic region and the FOXP3-positive cut-off value.     

Caveolin-1 Expression Level in Cancer Associated Fibroblasts Predicts Outcome in Gastric Cancer

Aims

Altered expression of epithelial or stromal caveolin-1 (Cav-1) is observed in various types of human cancers. However, the clinical significance of Cav-1 expression in gastric cancer (GC) remains largely unknown. The present study aims to explore the clinicopathological significance and prognostic value of both tumor cells and cancer associated fibroblasts (CAFs) Cav-1 in GC.

Methods and Results

Quantum dots immunofluorescence histochemistry was performed to examine the expression of Cav-1 in 20 cases of gastritis without intestinal metaplasia (IM), 20 cases of gastritis with IM and 286 cases of GC. Positive rates of epithelial Cav-1 in gastritis without IM, gastritis with IM and GC showed a decreasing trend (P = 0.012). Low expression of Cav-1 in CAFs but not in tumor cells was an independent predictor of poor prognosis in GC patients (P = 0.034 and 0.005 respectively in disease free survival and overall survival). Cav-1 level in tumor cells and CAFs showed no significant correlation with classic clinicopathological features.

Conclusions

Loss of epithelial Cav-1 may promote malignant progression and low CAFs Cav-1 level herald worse outcome of GC patient, suggesting CAFs Cav-1 may be a candidate therapeutic target and a useful prognostic marker of GC.