Clinicopathological and Prognostic Significance of Survivin Over-Expression in Patients with Esophageal Squamous Cell Carcinoma: A Meta-Analysis

Background

The prognostic significance of survivin for survival of patients with esophageal squamous cell carcinoma (ESCC) remains controversial. Thus, meta-analysis of the literatures was performed in order to demonstrate its expression impact on ESCC clinicopathological features and prognosis.

Methodology

Relevant literatures were searched using PubMed, EMBASE and Medline Databases. Revman5.0 software was used to pool eligible studies and summary hazard ratio (HR). Correlation between survivin expression and clinicopathological features of ESCC was analyzed.

Principal Findings

Final analysis of 523 patients from 7 eligible studies was performed. Combined HR of survivin location in nuclei suggested that survivin expression has an unfavorable impact on ESCC patients'' survival (n = 277 in 3 studies; HR = 1.89, 95% CI: 1.45–2.96; Z = 4.69; P<0.0001). Nevertheless, combined HR of survivin location in cytoplasm displayed that survivin expression has no significance for prognosis of ESCC patients (n = 113 in 2 studies; HR = 0.96, 95% CI: 0.96–5.69; Z = 0.04; P = 0.97); Combined odds ratio (OR) of survivin location in cytoplasm indicated that survivin expression is associated with ESCC advanced stage (n = 113 in 2 studies; OR = 0.36, 95% CI: 0.14–0.93; Z = 2.10; P = 0.04). Whereas, combined OR of survivin location in nuclei exhibited that survivin over-expression has no correlation with cell differentiation grade, lymph node status, depth of invasion, stage, and metastasis of ESCC.

Conclusions

This study showed that survivin expression detected by immunohistochemistry seems to be associated with a worse prognosis of ESCC patients. Survivin subcellular location may be an important factor impacting on ESCC development. Larger prospective studies should be performed to evaluate the status of survivin in predicting prognosis of patients with ESCC.     

Meta-Analysis: Prognostic Value of Survivin in Patients with Hepatocellular Carcinoma

Background

The expression of survivin is a promising prognostic indicator for some carcinomas. However, evidence for the prognostic value of survivin with respect to survival in hepatocellular carcinoma remains controversial.

Aim

To conduct a systematic review of studies evaluating survivin expression in hepatocellular carcinoma as a prognostic indicator.

Methods

The relevant literature was searched using PubMed, EMBASE, and Chinese biomedicine databases, and two meta-analyses were performed. One studied the association between survivin expression and the overall survival of patients with hepatocellular carcinoma, whereas the other studied the association between survivin expression and disease-free survival. Studies were pooled, and summary hazard ratios (HRs) were calculated. Subgroup analyses were also conducted.

Results

Fourteen eligible studies with a total of 890 patients were included in this study. Two meta-analyses were performed according to the different outcomes by which prognosis was valued. The combined HR of the overall survival studies was 2.33 (95% CI: 1.65–3.31). The combined HR of disease-free survival studies was 2.13 (95% CI: 1.65–2.75). These data appeared to be significant when stratified by detection method, the language of publication, and HR estimate. The heterogeneities were highly significant (I²>50%) when subgroup analyses of overall survival rate were conducted, whereas little heterogeneity was found when subgroup analyses of disease-free survival rate were carried out. The positive expression of survivin in the cytoplasm was significantly correlated with poor prognosis in HCC (HR>1).

Conclusions

This study showed that survivin expression was correlated with poor prognosis in patients with hepatocellular carcinoma, regardless whether they were assessed by overall survival or disease-free survival.     

宫颈鳞状细胞癌中ADAM17 的表达及其临床意义

目的:探讨去整合素-金属蛋白酶17(ADAM17)在宫颈鳞状细胞癌中的表达及其临床病理意义。方法:运用免疫组织化学法分别检测正常宫颈上皮、宫颈鳞状细胞癌及宫颈上皮内瘤样变组织中ADAM17的表达,并分析其与宫颈癌临床分期及淋巴结转移的相关性。结果:ADAM17在正常宫颈上皮组织切片中无明显表达,在宫颈上皮内瘤样变组织中少部分表达,呈浅黄色,在宫颈鳞状细胞癌中癌细胞大量表达,ADAM17表达呈棕褐色,数量较多且浓染。不同临床分期的宫颈鳞状细胞癌组织中ADAM17的阳性表达率比较存在显著统计学差异(P0.05),且随临床分期的上升,ADAM17的表达逐渐升高;有淋巴结转移的宫颈鳞状细胞癌组织中ADAM17的阳性表达率显著高于无淋巴结转移的宫颈鳞状细胞癌组织,差异具有统计学意义(P0.05)。结论:ADAM17蛋白在宫颈鳞状细胞癌组织中呈异常高表达,且与宫颈鳞状细胞癌的临床分期和淋巴结转移密切相关,通过检测ADAM17蛋白的表达可能有助于宫颈鳞状细胞癌的诊断、治疗和预后预测。     

VEGF在口腔鳞状细胞癌中的表达及其临床意义

目的:研究血管内皮生长因子(Vascular endothelial growth factor,VEGF)在口腔鳞状细胞癌中的表达及其临床意义.方法:免疫组化EnVisionTM法检测VEGF在57例手术治疗的原发性OSCC(口腔鳞状细胞癌)中的表迭.结果:①VEGF在OSCC中的阳性表达率为40.35%.②VEGF在不同发病部位组的表达:牙龈癌>舌癌>颊癌>唇癌,组间无统计学差异(P>0.05).③VEOF在不同病理分级组、不同预后组、不同年龄组、不同性别组的表达无显著性差异(P>0.05);淋巴结转移组的表达显著高于无转移组(P<0.05).结论:虽然VEGF的高表达可能在淋巴结转移中起一定的作用,但还不能作为预测口腔鳞状细胞癌临床生物学行为及预后的可靠指标.     

Prognostic Significance of Interleukin-8 and CD163-Positive Cell-Infiltration in Tumor Tissues in Patients with Oral Squamous Cell Carcinoma

Purpose

We investigated whether serum interleukin (IL)-8 reflects the tumor microenvironment and has prognostic value in patients with oral squamous cell carcinoma (OSCC).

Experimental Design

Fifty OSCC patients who received radical resection of their tumor(s) were enrolled. Preoperative sera were measured for IL-8 by ELISA. Expression of IL-8 and the infiltration of immune cells in tumor tissues were analyzed by an immunohistochemical staining of surgical specimens.

Results

We found that disease-free survival (DFS) was significantly longer in the Stage I/II OSCC patients with low serum IL-8 levels compared to those with high levels (p = 0.001). The tumor expression of IL-8, i.e., IL-8(T) and the density of CD163-positive cells in the tumor invasive front, i.e., CD163(IF) were correlated with the serum IL-8 level (p = 0.033 and p = 0.038, respectively), and they were associated with poor clinical outcome (p = 0.007 and p = 0.002, respectively, in DFS) in all patients. A multivariate analysis revealed that N status, IL-8(T) and CD163(IF) significantly affected the DFS of the patients. Further analysis suggested that combination of N status with serum IL-8, IL-8(T) or CD163(IF) may be a new criterion for discriminating between OSCC patients at high and low risk for tumor relapse. Interestingly, the in vitro experiments demonstrated that IL-8 enhanced generation of CD163-positive M2 macrophages from peripheral blood monocytes, and that the cells produced IL-10.

Conclusions

These findings indicate that IL-8 may be involved in poor clinical outcomes via generation of CD163-positive M2 macrophages, and that these factors in addition to N status may have prognostic value in patients with resectable OSCSS.     

影响口腔鳞状细胞癌患者预后的临床病理因素分析

目的:研究影响口腔鳞状细胞癌(Oral squamous cellcar cinoma,OSCC)术后患者预后的临床病理因素。方法:回顾性研究55例手术治疗的原发口腔鳞状细胞癌患者与预后相关的因素:年龄、性别、发病部位、颈部淋巴结转移情况、肿瘤细胞分化程度等。结果:平均发病年龄为57.35±12.02岁,牙龈鳞癌的复发转移率最高(45.5%),舌部第二(44%),颊部第三(37.5%),唇癌预后最好(0.0%)。术前颈部淋巴结转移情况、肿瘤细胞分化程度与预后有关。肿瘤细胞的分化程度与术前淋巴结转移无显著相关性。术前有颈部淋巴结转移合并中低分化与预后差相关。结论:口腔鳞状细胞癌的预后与发病部位无显著相关性。肿瘤中低分化及术前有淋巴结转移者易出现术后复发转移。     

影响口腔鳞状细胞癌患者预后的临床病理因素分析

目的：研究影响口腔鳞状细胞癌（Oral squamous cellcar cinoma,OSCC）术后患者预后的临床病理因素。方法：回顾性研究55例手术治疗的原发口腔鳞状细胞癌患者与预后相关的因素：年龄、性别、发病部位、颈部淋巴结转移情况、肿瘤细胞分化程度等。结果：平均发病年龄为57.35±12.02岁,牙龈鳞癌的复发转移率最高（45.5%）,舌部第二（44%）,颊部第三（37.5%）,唇癌预后最好（0.0%）。术前颈部淋巴结转移情况、肿瘤细胞分化程度与预后有关。肿瘤细胞的分化程度与术前淋巴结转移无显著相关性。术前有颈部淋巴结转移合并中低分化与预后差相关。结论：口腔鳞状细胞癌的预后与发病部位无显著相关性。肿瘤中低分化及术前有淋巴结转移者易出现术后复发转移。     

Prognostic Significance of E-Cadherin Expression in Hepatocellular Carcinoma: A Meta-Analysis

Backgrounds

Hepatocellular Carcinoma (HCC) is one of the most common malignancy of liver and HCC-related morbidity and mortality remains at high level. Researchers had investigated whether and how reduced E-cadherin expression impacted the prognosis of patients with HCC but the results reported by different teams remain inconclusive.

Methods

A systematic literature search was performed in all available databases to retrieve eligible studies and identify all relevant data, which could be used to evaluate the correlation between reduced E-cadherin expression and clinicopathological features and prognosis for HCC patients. A fixed or random effects model was used in this meta-analysis to calculate the pooled odds ratios (OR) and weighted mean differences (WMD) with 95% confidence intervals (CI).

Results

Total 2439 patients in thirty studies matched the selection criteria. Aggregation of the data suggested that reduced E-cadherin expression in HCC patients correlated with poor 1-, 3- and 5-year overall survival. The combined ORs were 0.50 (n = 13 studies, 95% CI: 0.37–0.67, Z = 4.49, P<0.00001), 0.39 (n = 13 studies, 95% CI: 0.28–0.56, Z = 5.12, P<0.00001), 0.40 (n = 11 studies, 95% CI: 0.25–0.64, Z = 3.82, P = 0.0001), respectively. Additionally, the pooled analysis denoted that reduced E-cadherin expression negatively impacts recurrence-free survival (RSF) with no significant heterogeneity. The pooled ORs for 1-, 3- and 5- year RSF affected by down-regulated E-cadherin were 0.73 (n = 6 studies, 95% CI: 0.54–1.00, Z = 1.95, P = 0.05), 0.70 (n = 6 studies, 95% CI: 0.52–0.95, Z = 2.32, P = 0.02), 0.66 (n = 5 studies, 95% CI: 0.48–0.90, Z = 2.64, P = 0.008). And what’s more, reduced E-cadherin expression tended to be significantly associated with metastasis (OR = 0.31, 95% CI: 0.16–0.60, Z = 3.50, P = 0.0005), vascular invasion (OR = 0.76, 95% CI: 0.59–0.98, Z = 2.14, P = 0.03), advanced differentiation grade (OR = 0.31, 95% CI: 0.21–0.45, Z = 6.04, P<0.00001) and advanced TMN stage (T3/T4 versus T1/T2) (OR = 0.61,95% CI:0.38–0.98, Z = 2.05, P = 0.04).

Conclusions

Reduced E-cadherin expression indicates a poor prognosis for patients with HCC, and it may have predictive potential for prognosis of HCC patients.     

Association between Tissue Expression of Toll-Like Receptor and Some Clinicopathological Indices in Oral Squamous Cell Carcinoma

Background:The oral squamous cell carcinoma (OSCC) composes about 90% of all head and neck cancers. The toll-like receptor (TLR)⁺ immune cells have potential of invasion and malignancy transformation. The aim of this study was assessment of possible associations between clinicopathological indices and TLR2 and TLR9 gene expression in OSCC.Methods:Forty-two OSCC samples with related healthy margins including 25 early and 17 advanced stages were gathered. The samples were classified histologically from grade I to II. The expression of TLR2 and TLR2 was evaluated by Real-time PCR. The patient’s disease-free survival (DFS) and overall survival (OS) were analyzed using SPSS V.23 software.Results:The expression of TLR2 and TLR9 genes in tumor tissues (especially in grade I and II) were higher than healthy surgical margin tissue (p< 0.001). TLR9 expression in grade II was statistically significant than grade I in tumor tissue (p< 0.001). TLR9 expression in advanced stage was statistically significant in compare to early stage (p= 0.012). In advanced stage both overall survival (p= 0.029) and disease-free survival (p= 0.012) were statistically lower than early stage. The follow-up time to recurrence in advanced stage was statistically lower than early stage (p= 0.007).Conclusion:Overexpression of TLRs 2, 9 play role in the pathogenesis and tumor development of OSCC and can be applied as biomarker in prognostic approaches.Key Words: Disease-free survival, Oral squamous cell carcinoma, Overall survival, TLR2, TLR9     

VEGF-C 在口腔鳞状细胞癌中的表达及其意义

目的:检测血管内皮生长因子-C(VEGF-C)在口腔鳞状细胞癌(鳞癌)和癌旁组织中的表达情况,探讨VEGF-C在口腔鳞癌的增殖、浸润和淋巴转移中的作用。方法:采用免疫组化方法检测60例口腔鳞癌病人癌组织和癌旁组织中VEGF-C的表达,应用图像分析系统进行分析,用Spearman相关分析研究其与病变部位、肿瘤大小、病理分级、临床分期及颈淋巴结转移之间的关系。结果:口腔鳞癌组织VEGF-C的表达明显高于癌旁组织(u=7.747,P<0.01),其表达强度与临床分期及淋巴结转移密切相关(r=0.564、0.706,P<0.05),与病变部位、大小、病理分级无关。结论:口腔鳞癌细胞分泌VEGF-C诱导癌周淋巴管增生扩张是发生区域淋巴结转移的重要因素之一,VEGF-C有望作为早期临床判断和预测颈淋巴结转移的指标之一。     

FAS/FASL Expression Profile as a Prognostic Marker in Squamous Cell Carcinoma of the Oral Cavity

FAS/FASL altered expression may cause tumor protecting immunomodulation, with a direct impact on patient prognosis. FAS expression was studied in 60 squamous cell carcinomas of the oral cavity. FAS expression did not show a significant association with tumor histopathological characteristics, but was significantly associated with lymph node positivity. FAS expression was significantly associated with disease specific death and negative FAS expression was an independent risk factor, increasing risk 4 times when compared to positive expression. When FAS and FASL expression results were combined, we were able to define high, intermediate and low risk profiles. Disease-free and disease-specific survival were significantly correlated with FAS/FASL expression profiles. The high risk category was an independent marker for earlier disease relapse and disease-specific death, with approximately 4- and 6-fold increased risk, respectively, when compared to the low risk profile. Risk profiles based on FAS/FASL expression showed that high risk was significantly associated with increased disease relapse and death, as well as shorter disease-free or disease-specific survival. This categorization, added to patient clinical data, may facilitate the choice of therapy, minimizing treatment failure and increasing disease control.     

Clinicopathological and Prognostic Significance of CD24 Overexpression in Patients with Gastric Cancer: A Meta-Analysis

Objective

The prognostic significance of CD24 expression for survival in patients with gastric cancer remains controversial. We conducted a meta-analysis to investigate the impact of CD24 expression on clinicopathological features and survival outcomes in gastric cancer.

Methods

A comprehensive literature search of the electronic databases PubMed, Embase, Web of Science and China National Knowledge Infrastructure (CNKI; up to April 8, 2014) was performed for relevant studies using multiple search strategies. Correlations between CD24 expression and clinicopathological features and overall survival (OS) were analyzed.

Results

A total of 1,041 patients with gastric cancer from 9 studies were included. The pooled odds ratios (ORs) indicated CD24 expression was associated with tumor depth (OR = 0.45, 95% confidence interval [CI]  = 0.32–0.63; P<0.00001), status of lymph nodes (OR = 0.40, 95% CI = 0.25–0.64; P = 0.0001) and tumor node metastasis (TNM) stage (OR = 0.56, 95% CI = 0.41–0.77; P = 0.0003). The pooled hazard ratio (HR) for OS showed overexpression of CD24 reduced OS in gastric cancer (HR = 1.99, 95% CI = 1.29–3.07, P = 0.002). Whereas, combined ORs showed that CD24 expression had no correlation with tumor differentiation or Lauren classifications.

Conclusion

CD24 overexpression in patients with gastric cancer indicated worse survival outcomes and was associated with common clinicopathological poor prognostic factors.     

舌鳞癌层粘连蛋白的表达及意义

采用免疫组织化学技术,研究了正常、异常增生组织、舌癌及舌癌淋巴结转移灶中层粘连蛋白的表达、分布及意义。结果发现：正常舌粘膜、轻度异常增生组织的基底膜处层粘连蛋白呈连续线状分布,中度和重度异常增生组织基底膜层粘连蛋白的分布有局部断裂。舌癌中层粘连蛋白的分布呈多种形式,分化好的舌癌层粘连蛋白呈线状,但明显不连续,分化差的舌癌中的层粘连蛋白常呈碎片状,而舌癌的淋巴结转移灶中层粘连蛋白的分布与原发灶相似。统计分析表明,层粘连蛋白的表达与舌癌的分化程度相关,而与舌癌的转移无关。观察结果表明：舌癌分化程度愈低,层粘连蛋白的缺损愈严重,层粘连蛋白的表达、分布特点可以作为判断癌恶性程度的指标,但不能判断舌癌的转移     

微小RNA miR-21和miR-31在口腔鳞癌组织中的表达及意义

目的:检测口腔鳞癌中微小RNA miR-21和miR-31的表达,探讨其与肿瘤发展的关系。方法:应用实时荧光定量PCR的方法检测72例口腔鳞癌,38例正常口腔粘膜miR-21和miR-31的表达,统计学分析其表达与肿瘤临床分期和病理分型的关系。结果:①口腔鳞癌组织与对照组比较,微小RNA miR-21和miR-31的表达都有显著增高(P0.05),其中miR-21的增高更为显著(P0.001)。②统计学分析表明,miR-21的表达在晚期鳞癌组织较早中期鳞癌组织增高更为显著(P0.01),在低分化鳞癌组织较中、高分化鳞癌组织增高更为显著(p0.001);MiR-31的表达水平在不同肿瘤临床分期和病理分型鳞癌组织中无明显差异(P0.05)。结论:miR-21和miR-31在口腔鳞癌发生发展过程中表达有明显增高,其中miR-21表达水平可作为潜在的口腔鳞癌临床分期分级和预后的指标。     

微小RNAmiR-21和miR-31在13腔鳞癌组织中的表达及意义

目的：检测口腔鳞癌中微小RNA miR-21和miR-31的表达,探讨其与肿瘤发展的关系。方法：应用实时荧光定量PCR的方法检测72例口腔鳞癌,38例正常口腔粘膜miR-21和miR-31的表达,统计学分析其表达与肿瘤临床分期和病理分型的关系。结果：①口腔鳞癌组织与对照组比较,微小RNA miR-21和miR-31的表达都有显著增高（P〈0.05）,其中miR-21的增高更为显著（P〈0.001）。②统计学分析表明,miR-21的表达在晚期鳞癌组织较早中期鳞癌组织增高更为显著（P〈0.01）,在低分化鳞癌组织较中、高分化鳞癌组织增高更为显著（p〈0.001）;MiR-31的表达水平在不同肿瘤临床分期和病理分型鳞癌组织中无明显差异（P〉0.05）。结论：miR-21和miR-31在口腔鳞癌发生发展过程中表达有明显增高,其中miR-21表达水平可作为潜在的口腔鳞癌临床分期分级和预后的指标。     

Anxa2, Stat3 在口腔鳞状细胞癌中的表达及意义

目的:探讨膜联蛋白A2(Anxa2)和细胞信号转导和转录激活因子3(Stat3)在口腔鳞癌组织中的表达及其临床意义。方法:选择口腔鳞癌石蜡标本80例为实验组,20例正常口腔黏膜组织为对照组。应用免疫组织化学法检测Anxa2和Stat3蛋白的阳性表达,并进行结果判定,采用x2和Spearman等级相关分析法分析二者表达差异性及其相关性。结果:Anxa2、Stat3在病例组中的阳性表达率,分别为81.3%(65/80)、87.5%(70/80),明显高于对照组中的表达率,25.0%(5/20)、30.0%(6/20),且差异有统计学意义(P0.05),Anxa2和Stat3蛋白表达水平与口腔鳞癌的分期、淋巴结转移及分化程度有密切关系。Spearman等级相关分析Anxa2和Stat3在口腔鳞癌组织中蛋白的表达呈正相关(r=0.302,P0.01)。结论:Anxa2、Stat3在OSCC的发生和转移过程中均具有重要的作用,且二者间也有相互作用的关系。     

原发性口腔鳞癌组织及血清中内皮抑素表达的意义

目的：探讨原发性口腔鳞癌患者组织和血清中内皮抑素表达及与肿瘤分期、分级的关系。方法：采用免疫组化方法检测36例口腔鳞癌和12例正常口腔粘膜组织中内皮抑素表达情况。ELISA法检测36例口腔鳞癌患者术前血清内皮抑素水平,14例健康者血清做对照。结果：内皮抑素主要见于肿瘤组织细胞质。正常口腔粘膜中内皮抑素表达率为7.15%,口腔鳞癌组织中内皮抑素阳性率为76.44%,其中G1、G2、G3级阳性率分别为47.21%、79.17%、90.90%,病理分级间比较差异有统计学意义（P〈0.05）。口腔鳞癌患者血清中内皮抑素水平（49.62±1.72）ng/mL显著高于健康对照者（5.60±0.37）ng/mL（P〈0.05）,TNM分期III、IV期肿瘤患者血清内皮抑素水平显著高于I和II期（P〈0.05）。结论：口腔鳞癌患者组织和血清中内皮抑素表达显著升高,并与肿瘤分期、分级相关,检测内皮抑素表达有助于判断口腔鳞癌恶性程度。     

原发性口腔鳞癌组织及血清中内皮抑素表达的意义

目的:探讨原发性口腔鳞癌患者组织和血清中内皮抑素表达及与肿瘤分期、分级的关系。方法:采用免疫组化方法检测36例口腔鳞癌和12例正常口腔粘膜组织中内皮抑素表达情况。ELISA法检测36例口腔鳞癌患者术前血清内皮抑素水平,14例健康者血清做对照。结果:内皮抑素主要见于肿瘤组织细胞质。正常口腔粘膜中内皮抑素表达率为7.15%,口腔鳞癌组织中内皮抑素阳性率为76.44%,其中G1、G2、G3级阳性率分别为47.21%、79.17%、90.90%,病理分级间比较差异有统计学意义(P<0.05)。口腔鳞癌患者血清中内皮抑素水平(49.62±1.72)ng/mL显著高于健康对照者(5.60±0.37)ng/mL(P<0.05),TNM分期III、IV期肿瘤患者血清内皮抑素水平显著高于I和II期(P<0.05)。结论:口腔鳞癌患者组织和血清中内皮抑素表达显著升高,并与肿瘤分期、分级相关,检测内皮抑素表达有助于判断口腔鳞癌恶性程度。     

CD9在口腔鳞状细胞癌中的表达水平及其临床意义

目的:口腔鳞状细胞癌是一类极易发生局部侵袭和淋巴结转移的恶性肿瘤,CD9蛋白在多种肿瘤的发生发展及侵袭转移过程中起到重要作用,本研究旨在分析CD9蛋白在口腔鳞状细胞癌中的表达水平及其临床意义。方法:收集我院诊断明确的口腔鳞癌肿瘤患者石蜡标本合计80例,通过免疫组化手段对CD9蛋白表达水平进行评价,并根据CD9蛋白的表达水平分组,分析患者的临床病理学特征与CD9蛋白的关系。结果:CD9在正常组织和癌旁组织正常表达,在肿瘤组织中表达率低,其表达水平和口腔鳞癌的分化程度,淋巴结转移及最终分期有相关性(P0.05)。结论:本研究结果揭示,CD9在口腔鳞状细胞癌的发生发展中起到重要作用,CD9蛋白水平的低表达或不表达可能预测着肿瘤具有更明显的恶性生物学行为,并可能成为口腔鳞状细胞癌预后的生物学指标及基因治疗的新靶点。