长链非编码RNA BANCR在食管鳞癌中的表达及对细胞增殖和侵袭能力的影响

目的:探索长链非编码RNA BANCR与食管鳞癌(esophageal squamous cell carcinoma ESCC)临床病理特征以及预后的关系,以及对于ESCC细胞增殖,迁移和侵袭能力的影响。方法:使用实时荧光定量PCR(q RT-PCR)技术检测ESCC组织及多个细胞系中BANCR的表达水平,分析其与临床病理特征及预后的关联,用小干扰RNA(si RNA)干扰BANCR后用CCK8法检测其对ESCC细胞生长的影响,使用transwell法检测对细胞侵袭和转移能力的影响。结果:相对于癌旁组织,有86%(123/142)的癌组织中BANCR表达量升高,BANCR在癌组织中的相对表达水平与肿瘤的组织学分级、TNM分期和淋巴结转移数量相关(P均0.05)。BANCR在本文涉及的八株ESCC细胞中的表达量均高于正常食管上皮细胞(Het1A)。在TE10和KYSE30细胞中敲降BANCR后可明显降低细胞生长速率,并抑制细胞的侵袭和迁移能力(P0.01)。结论:BANCR在ESCC组织和细胞中表达显著上调。并能增强ESCC细胞的增殖和侵袭能力,有希望成为一种新的辅助ESCC早期诊断和预后判断的肿瘤分子标志物。     

Decreased tumstatin-mRNA is associated with poor outcome in patients with NSCLC

Tumstatin is a candidate tumor suppressor that plays an important role in tumor growth and angiogenesis. The purpose of this study was to evaluate the correlation between tumstatin-mRNA expression and the clinicopathologic characteristics, tumor angiogenesis, outcome of patients with non-small cell lung cancer (NSCLC). Specimens from 68 patients with NSCLC were recruited in this study. Tumstatin-mRNA expression and protein level in tumor tissues were quantified respectively by quantitative RT-PCR and ELISA. Microvessel density (MVD) was determined by CD34 immunostaining. The correlation of tumstatin-mRNA expression levels with clinicopathologic variables, tumor angiogenesis, and prognosis was analyzed. Tumstatin-mRNA expression levels were decreased in tumor. Tumstatin-mRNA expression level was significantly correlated with its protein level in tumor (r = 0.562; P = 0.001). Tumstatin-mRNA expression levels in poorly differentiated tumor tissues were significantly lower than in well-differentiated tumor tissues (P < 0.004). Furthermore, tumor tumstatin-mRNA expression were also significantly related to tumor pathologic stage (P = 0.032) and MVD (r = -0.77, P < 0.0001). Overall survival (OS) and disease-free survival (DFS) analysis indicated that NSCLC patients with low tumstatin-mRNA expression had poorer OS and DFS than those with high expression (P = 0.015 and 0.037; respectively). Multivariable Cox regression analysis revealed that the tumstatin-mRNA expression could be an independent prognostic indicators in both DFS and OS. Tumstatin-mRNA expression levels are down-regulated in NSCLC tissues. Tumstatin-mRNA expression level correlates with prognosis, which suggests that tumstatin-mRNA is a new potential independent marker of favorable prognosis in NSCLC.     

MMP14在非小细胞肺癌中的表达及其与预后的关系

肺癌5年生存率低,侵润和转移是导致其死亡的主要原因.探讨MMP14(matrix mettallo proteinase 14)在非小细胞肺癌(non-small cell lung cancer,NSCLC)组织中的表达,及其与浸润转移和预后的关系.通过采用免疫组化检测92例NSCLC组织及25例癌旁正常组织中MMP14蛋白的表达,并分析其与临床病理学特征及预后的关系.免疫组化结果显示,MMP14蛋白在NSCLC组织中表达的阳性率为64.1%(59/92),显著高于癌旁正常组8%(2/25)(P<0.001).MMP14阳性率与NSCLC的分化程度、T分期、淋巴结转移和TNM分期相关(P<0.05),而与性别、年龄、吸烟及组织学类型无关(P>0.05).Kaplan-meier生存曲线显示,MMP14阳性表达组的患者5年生存期显著低于阴性表达组(P=0.004).Cox多因素回归分析显示,MMP14不是NSCLC的独立预后因素(P>0.05).MMP14在肺癌的分化、浸润和转移中扮演着重要的作用,并对生存期有一定的影响.     

甲状腺癌组织中ALCAM 的表达及其与临床病理参数及预后的关系

目的:探讨甲状腺癌组织中活化白细胞黏附分子(activated leukocyte cell adhesion molecule,ALCAM)的表达及其与临床病理参数及预后的关系。方法:选择2011年1月到2013年1月在我院确诊为甲状腺癌的患者60例作为研究对象。收集所有患者甲状腺癌组织及其癌旁正常组织标本,采用免疫组织化学法检测不同组织中ALCAM蛋白表达,分析其与甲状腺癌患者临床病理参数的相关性,并对所有患者随访3年以上,并记录3年生存率。结果:ALCAM蛋白在甲状腺癌组织中的总阳性率为71.67%,明显高于癌旁正常组织的31.67%(P0.05)。ALCAM蛋白在高分化型甲状腺癌组织中的表达率明显高于低分化及无分化型癌组织(P0.05)。ALCAM蛋白高表达的甲状腺癌患者的3年生存率为81.45%,明显高于ALCAM蛋白低表达者的51.32%(P0.05)。结论:组织中ALCAM蛋白表达与甲状腺癌的发生、发展及患者预后密切相关。     

Overexpression of PTP1B in human colorectal cancer and its association with tumor progression and prognosis

Protein tyrosine phosphatase 1B (PTP1B) is a non-transmembrane protein tyrosine phosphatase that has been implicated in cancer pathogenesis. However, the expression level and the role of PTP1B in the development and prognosis of colorectal cancer (CRC) remain unclear. In this study, the expression of PTP1B in CRC tissues and matched noncancerous tissues were detected by using immunohistochemistry, real-time PCR and Western blotting. The correlations between PTP1B expression level and clinicopathologic characteristics and patient survival were analyzed. We found that PTP1B expression was significantly higher in CRC tissues compared with matched non-tumour tissues. Statistical analysis showed that the PTP1B expression was correlated with tumor differentiation, tumor invasion, lymph node metastasis, and TNM stage. Patients with higher expressions of PTP1B had the lower survival (P = 0.012). Taken together, our results suggest that PTP1B expression might play a critical role in the progression of CRC and may serve as a valuable prognostic biomarker for CRC.     

NGAL and NGALR overexpression in human hepatocellular carcinoma toward a molecular prognostic classification

Aim: Neutrophil gelatinase-associated lipocalin (NGAL) and its cell surface receptor, NGALR, have been implicated in tumorigenesis and tumor progression of various human malignant neoplasms. In particularly, it has been demonstrated that NGAL is overexpressed in hepatocellular carcinoma (HCC) tissues and closely associated with the proliferation and invasion of HCC cells. The aim of this study was to investigate the clinical significance of NGAL and NGALR in HCC. Methods: Expression of NGAL and NGALR was evaluated by immunohistochemistry in tumor tissues from 138 patients who underwent curative resection of HCC. The association of NGAL or NGALR expression with the clinicopathologic features was analyzed. Univariate and multivariate analyses were performed to evaluate the prognostic value of NGAL and/or NGALR expression for HCC patients. Results: The expression levels of NGAL and NGALR were both up-regulated in HCC tissues, and to be associated with vascular invasion (both P=0.03), TNM stage (both P=0.004), and tumor recurrence (both P<0.001). A positive correlation between expression of the two markers was also observed (r=0.89; P<0.001). Additionally, survival analysis showed that high expression of NGAL or NGALR was significantly associated with poor prognosis for patients with HCC (both P=0.003). Patients with high expression of both NGAL and NGALR had a shorter overall survival (P<0.001) than those with low expression of both. Furthermore, multivariate analysis showed both NGAL and NGALR were independent predictors of overall survival. Conclusion: Our data demonstrate for the first time that the up-regulations of NGAL and NGALR expression in HCC were both significantly correlated with unfavorable clinicopathologic features and independent poor prognostic factor for overall survival in patients. These findings suggest that NGAL and NGALR expression might be served as novel prognostic factors and potential therapeutic targets in HCC.     

Downregulation of tumor suppressor QKI in gastric cancer and its implication in cancer prognosis

Gastric cancer (GC) is the fourth most common cancer and second leading cause of cancer-related death worldwide. RNA-binding protein Quaking (QKI) is a newly identified tumor suppressor in multiple cancers, while its role in GC is largely unknown. Our study here aimed to clarify the relationship between QKI expression with the clinicopathologic characteristics and the prognosis of GC. In the 222 GC patients' specimens, QKI expression was found to be significantly decreased in most of the GC tissues, which was largely due to promoter hypermethylation. QKI overexpression reduced the proliferation ability of GC cell line in vitro study. In addition, the reduced QKI expression correlated well with poor differentiation status, depth of invasion, gastric lymph node metastasis, distant metastasis, advanced TNM stage, and poor survival. Multivariate analysis showed QKI expression was an independent prognostic factor for patient survival.     

Laminin-5 gamma 2 chain expression correlates with unfavorable prognosis in colon carcinomas.

Expression of the gamma 2 chain at the invasive front of different tumors has indicated an important role for laminin-5 in cell migration during tumor invasion and tissue remodeling. As there is considerable need for reliable invasion and prognostic markers we evaluated the correlation of laminin-5 gamma 2 chain expression with clinicopathologic parameters and patient survival in 93 primary colon carcinomas. Epithelial cells of normal mucosa were consistently negative for staining. In contrast, positive cytoplasmic staining was observed in 89 tumors (96%). Twenty-four (26%) cases were scored as sparse, 34 (37%) as moderate, and 31 (33%) as frequent gamma 2 chain expression. There was a significant association of laminin-5 gamma 2 chain expression and local invasiveness of colon carcinomas according to Dukes stage (A-C) (p=0.001) and tumor budding (p<0.001). A statistical significance could also be noted in decreasing tumor differentiation (p<0.001) and correlation to tumor size (p=0.032). No correlation was observed to tumor site. Univariate analysis identified laminin-5 (p=0.010), tumor differentiation (p=0.006) and Dukes grade (p<0.001) as significant variables in predicting prognosis. However, by multivariate analyses, this study could not demonstrate that laminin-5 gamma 2 chain expression is an independent predictive factor for survival.The results indicate that laminin-5 gamma 2 chain expression is up-regulated during the progression of human colon cancer and that it plays a role in the aggressiveness of these tumors. Demonstration of laminin-5 gamma 2 chain positivity also facilitates detection of individual cells or minor cell clusters invading the surrounding stroma.Figures on http://www.esacp.org/acp/2001/22-4/lenander.htm.     

Surgical site infections following colorectal cancer surgery: a randomized prospective trial comparing common and advanced antimicrobial dressing containing ionic silver

Background

The role of annexin II in the development and progression of gastric cancer was explored.

Methods

Real-time PCR was conducted to detect annexin II and S100A6 mRNA expression. Protein expressions of annexin II and S100A6 were also examined by immunohistochemistry in 436 clinicopathologically characterized gastric cancer cases.

Results

The expression of annexin II and S100A6 mRNA differ significantly among gastric tumor tissue and matched non-cancerous gastric mucosa. Protein levels of annexin II and S100A6 were up-regulated in gastric cancer compared with adjacent non-cancerous tissues. High expression of annexin II correlated with age, location of tumor, size of tumor, differentiation, histological type, depth of invasion, vessel invasion, lymph node metastasis, distant metastasis and Tumor, Node, Metastasis (TNM) stage, and also with expression of S100A6. Further multivariate analysis suggested that expression of annexin II and S100A6 were independent prognostic indicators for gastric cancer. Cumulative five-year survival rates of patients with high expression of both annexin II and S100A6 was significantly lower than those with low expression of both.

Conclusion

Expression of annexin II in gastric cancer was significantly associated with depth of invasion, lymph node metastasis and distant metastasis, TNM stage, high S100A6 expression, and poor prognosis. Annexin II and S100A6 proteins could be useful prognostic marker to predict tumor progression and prognosis in gastric cancer.     

宫颈癌组织RACK-1、Lgr5表达与临床病理特征及预后的关系

目的:探讨宫颈癌(CC)组织激活的蛋白激酶C受体1(RACK-1)、富含亮氨酸重复序列的G蛋白偶联受体5(Lgr5)表达与临床病理特征及预后的关系。方法:选取2012年1月-2016年1月于三峡大学附属仁和医院接受手术治疗的134例CC患者作为研究对象,选取CC组织以及对应的癌旁正常组织,同时选取该院因宫颈良性病变行肿物剥除或附件切除的134例患者的正常宫颈组织作为对照,采用免疫组化链霉素抗生物素蛋白-过氧化物酶连(SP)法对各组织进行免疫组化染色,依据阳性细胞率和染色强度分析CC组织中RACK-1、Lgr5的表达情况,并分析RACK-1、Lgr5表达与CC患者临床病理特征的相关性,分析Lgr5及RACK-1不同阳性表达强度的CC患者的预后。结果:CC组织中RACK-1、Lgr5阳性表达率高于癌旁组织和正常宫颈组织,差异有统计学意义(P0.05);RACK-1、Lgr5阳性表达与TNM分期、肿瘤分化程度、淋巴结转移、脉管内癌栓相关(P0.05),与患者的年龄、肿瘤大小、病理类型、肿瘤浸润深度、宫旁侵犯、手术切缘无关(P0.05);Lgr5、RACK-1阳性高表达组患者的3年生存率、生存时间低于Lgr5、RACK-1阳性低表达组患者,差异有统计学意义(P0.05)。结论:RACK-1、Lgr5在CC组织中表达上调,并与部分临床病理特征及预后有关,检测RACK-1、Lgr5有助于CC患者的诊断及预后评估。     

Plectin promotes migration and invasion of cancer cells and is a novel prognostic marker for head and neck squamous cell carcinoma

Head and neck squamous cell carcinoma (HNSCC) is usually found at a late stage and distant metastasis occurs at high frequency; therefore, novel prognostic markers are needed. This study was aimed to identify novel tumor markers in HNSCC. We identified 65 proteins which were significantly increased or decreased in the tumors by 2D-DIGE using 12 HNSCC and adjacent non-cancer tissues. Western blotting and immunohistochemical analysis confirmed that the expression of plectin was significantly increased in most cancer tissues as compared with non-cancer tissues. Strikingly, the suppression of endogenous plectin using siRNA inhibited the proliferation, migration and invasion of HNSCC cells and down-regulated Erk 1/2 kinase. Furthermore, immunohistochemistry using paraffin-embedded tissues from 62 patients showed not only that the frequency of recurrence was correlated with the plectin expression but that the prognosis of patients with a high plectin was extremely poor. Moreover, the survival rate of patients with a high plectin was significantly lower than that of patients with low E-cadherin levels, which is known to correlate with the poor prognosis of HNSCC. Our findings suggest that plectin promotes the migration and invasion of HNSCC cells through activation of Erk 1/2 kinase and is a potential prognostic biomarker of HNSCC.     

Expression and Biologic Significance of Adiponectin Receptors in Papillary Thyroid Carcinoma

Obesity is associated with a higher incidence of thyroid cancer. Adiponectin is one of the most abundant adipokines with a pleiotropic role in metabolism and in the development and progression of cancer. It has been shown that circulating adiponectin level is inversely associated with the risk of thyroid cancer. This study aimed to investigate the possible association between the expression of adiponectin receptors (AdipoR1 and AdipoR2) and clinicopathological variables in papillary thyroid cancer. We found that protein levels of AdipoR1 and AdipoR2 were increased in some thyroid cancer specimens compared with adjacent normal thyroid tissues. Thyroid cancer cells expressed AdipoR1 and AdipoR2, which were attenuated by histone deacetylase inhibitors valproic acid and trichostatin A. Adiponectin stimulated AMP-activated protein kinase phosphorylation in thyroid cancer cells. We further determined the expression of AdipoR1 and AdipoR2 by immunohistochemical staining in primary tumor samples and metastatic lymph nodes. AdipoR1 was expressed in 27 % of primary tumors and AdipoR2 in 47 %. Negative expression of both adiponectin receptors was significantly associated with extrathyroidal invasion, multicentricity, and higher TNM stage. There was a trend toward decreased disease-free survival in patients with negative tumor expression of AdipoR1 and AdipoR2 (log-rank P = 0.051). Collectively, overexpression of adiponectin receptors was observed in some tumor tissues of papillary thyroid cancer and was associated with a better prognosis.     

The role of CXC chemokine ligand 4/CXC chemokine receptor 3-B in breast cancer progression

Chemokines and their receptors participate in the development of cancers by enhancing tumor cell proliferation, angiogenesis, invasion, metastasis and penetration of tumor immune cells. It remains unclear whether CXC chemokine ligand 4 (CXCL4)/CXC chemokine receptor 3-B (CXCR3-B) can be used as an independent molecular marker for establishing prognosis for breast cancer patients. We evaluated CXCL4 and CXCR3-B expression in 114 breast cancer tissues and 30 matched noncancerous tissues using immunohistochemistry and western blot, and determined the correlation between their expression and clinicopathologic findings. We observed that breast cancer tissues express CXCL4 strongly and CXCR3-B weakly compared to noncancerous tissues. Strong CXCL4 expression was detected in 94.7% and weak CXCR3-B expression was detected in 78.9% of the tissues. Therefore, CXCL4/CXCR3-B might play a crucial role in breast cancer progression. We found no significant correlation between CXCL4 and age, tumor stage, tumor grade or TNM stage. CXCR3-B was associated significantly with tumor grade. Moreover, the Chi-square test of association showed that the expression of CXCL4/CXCR3-B might be an independent prognostic marker for breast cancer. Therefore, we suggest that CXCR3-B is an indicator of poor prognosis and may also be a chemotherapeutic target.     

赖氨酰氧化酶样蛋白2在肾细胞癌中的表达及其临床意义

为探究赖氨酰氧化酶样蛋白2 (lysyl oxidase like 2, LOXL2)与肾细胞癌(renal cell carcinoma, RCC)的关系,本研究采用免疫组织化学方法检测58例RCC组织及13例癌旁组织中LOXL2的表达水平,并利用统计学方法进一步分析LOXL2与临床病理参数和预后之间的关系。研究显示,LOXL2在癌组织和癌旁组织的阳性表达率分别为68.96%和23.08%,差异具有统计学意义(p<0.05)。LOXL2阳性表达与患者的临床分期和肾包膜浸润相关(p<0.05),但是与患者的性别、年龄、吸烟、病理类型、肿瘤大小和肿瘤分级均无相关性(p>0.05)。采用Kaplan-Meier法和Log-Rank检验分析LOXL2与术后生存时间的关系,实验显示LOXL2阳性组和阴性组患者的5年生存率分别为61.58%和89.46%,差异具有统计学意义(p<0.05)。我们的研究表明LOXL2在肾癌中过表达,其可能在肾癌的侵袭和转移过程中发挥作用,可作为预后的分子标记物。     

High Level of COP1 Expression is Associated with Poor Prognosis in Primary Gastric Cancer

COP1 (constitutive photomorphogenic 1, also known as RFWD2) is a p53-targeting E3 ubiquitin ligase containing RING-finger, coiled-coil, and WD40-repeat domains. Recent studies have identified that COP1 is overexpressed in several cancer types and that increased COP1 expression promotes cell proliferation, cell transformation, and tumor progression. In the present study, we investigated the expression and prognostic value of COP1 in primary gastric cancer. To investigate the role of the COP1 gene in primary gastric cancer pathogenesis, real-time quantitative PCR and western blotting were performed to examine COP1 expression in paired cancerous and matched adjacent noncancerous gastric tissues. The results revealed high COP1 mRNA (P=0.030) and protein (P=0.008) expression in most tumor-bearing tissues compared with the matched adjacent non-tumor tissues. The correlated protein expression analysis revealed a negative correlation between COP1 and p53 in gastric cancer samples (P=0.005, r=-0.572). Immunohistochemical staining of gastric cancer tissues from the same patient showed a high COP1 expression and a low p53 expression. To further investigate the clinicopathological and prognostic roles of COP1 expression, we performed immunohistochemical analysis of 401 paraffin-embedded gastric cancer tissue blocks. The data revealed that high COP1 expression was significantly correlated with T stage (P=0.030), M stage (P=0.048) and TNM stage (P=0.022). Consistent with these results, we found that high expression of COP1 was significantly correlated with poor survival in gastric cancer patients (P<0.001). Cox regression analyses showed that COP1 expression was an independent predictor of overall survival (P<0.001). Our data suggest that COP1 could play an important role in gastric cancer and might serve as a valuable prognostic marker and potential target for gene therapy in the treatment of gastric cancer.     

Overexpression of integrin-linked kinase (ILK) is associated with tumor progression and an unfavorable prognosis in patients with colorectal cancer

Integrin-linked kinase (ILK), an intracellular serine-threonine kinase, has been reported to be overexpressed in multiple types of human malignancies, including colorectal cancer (CRC). The prognostic value of ILK in CRC, however, remains unknown. In the present study, expression of ILK in 25 paired primary CRC samples and adjacent noncancerous tissues were quantified using real-time PCR and Western blotting. ILK protein expression was analyzed in 102 archived, paraffin-embedded CRC samples using immunohistochemistry. The correlation between ILK expression and clinicopathological factors was evaluated by the χ² test. Patients’ overall survival was analyzed by Kaplan–Meier method. We found that both ILK mRNA and protein expression levels were significantly up-regulated in primary CRC samples compared with their corresponding normal tissues. Immunohistochemical analysis revealed relative high expression of ILK in 43 of 102 (42.2 %) primary CRC samples. Statistical analysis showed a significant correlation of ILK expression with tumor differentiation, lymph node metastasis, tumor invasion, and tumor-node-metastasis stage. Patients with tumors displaying high-level ILK expression showed significantly shorter overall survival (P = 0.028, log-rank test). More importantly, multivariate analysis indicated that high ILK protein expression was an independent prognostic factor for CRC patients (P = 0.026). Taken together, our data suggest that ILK overexpression is associated with tumor progression and a poor prognosis in CRC patients and may represent a novel potential prognostic marker for patients with CRC.