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1.

Background

The present study examined the clinical significance of metastasis-associated protein 1 (MTA1) in the progression and patient survival of gastric cancer.

Methods

Paraffin-embedded resected tissues of gastric cancer mucosa (n?=?436) and adjacent normal mucosa (n?=?92) were assessed immunohistochemically for MTA1 protein, and scored according to the percentage of cells positively stained for MTA1 combined with stain intensity. Associations between MTA1 staining scores and clinicopathological factors, including survival time, were evaluated.

Results

The staining scores for MTA1 were significantly higher in gastric cancer tissues than in matched normal tissues. MTA1 scores positively correlated with tumor size, depth of invasion, presence of lymph node metastasis, lymphatic involvement, venous invasion, distal metastasis, and advanced clinical staging. Patients with high MTA1 scores in gastric cancer tissues had a significantly lower five-year survival rate compared with patients with low MTA1 scores. The multivariate analysis indicated that MTA1 protein levels in resected gastric cancer tissues, as reflected by immunohistochemical staining, are an independent prognostic index of gastric carcinoma (P?<?0.01).

Conclusion

MTA1 immunopositivity was significantly associated with progression of gastric cancer, and may be helpful in gastric cancer prognosis.  相似文献   

2.

Background

To assess the prognostic importance of carbonic anhydrase IX (CA IX), a hypoxic biomarker, after neoadjuvant treatment in Stage III non-small cell lung cancer (NSCLC) patients.

Methods

Tissue CA IX expression was examined after surgical resection in 77 patients who had undergone neoadjuvant treatment. The effects of CA IX overexpression and other clinical factors on disease-free survival and overall survival were investigated.

Results

In multivariate analysis, number of neoadjuvant chemotherapy (CT) courses and gender emerged as significant independent predictors for disease-free survival, where administration of 2–3 courses of neoadjuvant chemotherapy (CT) (HR, 3.2 [95% CI 1.3–7.6], p?=?0.009) and female gender were associated with poor survival (HR, 3.2 [95% CI 1.3–7.7], p?=?0.009). The only significant independent predictor for overall survival was recurrence (HR, 5.6 [95% CI 2.4–12.8], p?<?0.001). On the other hand, CA IX overexpression was not associated with disease free survival (p?=?0.560) or overall survival (p?=?0.799).

Discussion

Our results do not suggest a prognostic role for CA IX overexpression in stage III NSCLC patients who received neoadjuvant treatment.  相似文献   

3.

Background

Esophageal squamous cell carcinoma (ESCC) is a common cancer in East Asia and some other parts of the world with a dismal prognosis. CD51 (integrin αv),a transmembrane glycoprotein responsible for cell-to-matrix binding has been found to enhance tumor progression. However, its expression and clinicopathological significance in ESCC tumors are not fully understood. The purpose of this study was to investigate the expression level of CD51 and to explore its clinicopathological significance in ESCC.

Methods

The expression of CD51 in 122 ESCC samples was examined by immunohistochemistry and its clinicopathological significance was evaluated.

Results

The expression of CD51 was observed in tumor cell membrane and/or cytoplasm, with a positive rate of 48.36% (59/122). High expression of CD51 was significantly associated with lymph node metastasis (P?=? 0.031), tumor size (P?=? 0.028) and invasive depth (P?=? 0.027). Kaplan-Meier analysis revealed that positive expression of CD51 was correlated with poor overall survival of ESCC patients (P?=? 0.015). Multivariate analysis suggested that CD51 was an independent prognositic factor for ESCC (hazard ration = 1.604; 95% CI, 1.086–2.368; P?=? 0.017).

Conclusion

These data suggested CD51 was a predictor for the prognosis of ESCC patients.  相似文献   

4.

Background

Tripartite motif‐containing protein 44 (TRIM44) has been recently identified as a novel oncogene that is overexpressed in several types of human cancers; however, its role in endometrial cancer (EC) remains unknown. The purpose of the current study was to investigate the TRIM44 protein expression and clinicopathological significance of TRIM44 in EC.

Methods

Paraffin-embedded surgical specimens were collected from 143 patients with EC for the immunohistochemical analysis of TRIM44 expression. Western blotting was performed to evaluate differences in TRIM44 protein expression in EC and normal endometrial tissues.

Results

TRIM44 expression was low in normal tissues and high in EC tissues (P?<?0.001). TRIM44 overexpression was significantly associated with the Federation of Gynecology and Obstetrics (FIGO) stage, histological grade, depth of myometrial invasion and lymph node metastasis (P?<?0.05). Moreover, TRIM44 expression was an independent prognostic factor for both overall survival and disease-free survival in patients with EC (both P?<?0.05).

Conclusions

The present study provides evidence that TRIM44 predicts the risk of development and prognosis of EC, highlighting its potential application as a therapeutic target for this malignancy.  相似文献   

5.

Objective

The aim of this study was to determine the clinicopathological significance and potential prognostic role of SIRT1 expression in colorectal cancer (CRC) using immunohistochemistry and meta-analysis.

Methods

Immunohistochemistry was performed on 265 archival paraffin-embedded human CRC specimens to investigate the correlation between SIRT1 expression and clinicopathological characteristics, including patient survival. To elucidate the potential prognostic value of SIRT1 expression, a meta-analysis was performed using data on 2132 patients from eight eligible studies.

Results

SIRT1 was highly expressed in 24.5% of the 265 CRC specimens analyzed. High SIRT1 expression correlated with vascular invasion (P?=? 0.041). High SIRT1 expression also significantly correlated with expression of SNAI (P?=? 0.001), but not E-cadherin (P?=? 0.958). However, there was no significant correlation between SIRT1 expression and other clinicopathological parameters. High SIRT1 expression in the CRC specimens significantly correlated with a worse overall survival rate, independent of SNAI expression. However, based on the meta-analysis, high SIRT1 expression was not significantly correlated with overall survival rates [hazard ratio (HR) 1.111, 95% confidential interval (CI) 0.799–1.544].

Conclusion

In our retrospective study, high SIRT1 expression significantly correlated with vascular invasion and a worse prognosis. However, because the results from the meta-analysis differed the retrospective arm of our study, additional cumulative studies are needed to determine the prognostic value of SIRT1 in CRC.  相似文献   

6.

Objective

The prognostic value of vimentin expression in Gastric Cancer (GC) has been assessed for years while the results are still in dispute. Thus, we performed a meta-analysis to determine the effect of vimentin immunohistochemical (IHC) expression on the prognosis of GC.

Methods

Literature searches were performed in PubMed and Embase. The meta-analysis examined the association of vimentin IHC expression with prognosis and clinicopathological characteristics of GC patients.

Results

In total, ten studies involving 1598 cases were enrolled in this meta-analysis. Vimentin positive expression was significantly correlated with poor overall survival (OS) in GC patients (HR?=?2.05, 95% CI: 1.29–3.24) but there was a significant degree of heterogeneity (I2?=?77%, P?=?0.0006). Subgroup analysis indicated that vimentin expression had an unfavorable impact on OS in Chinese patients (HR?=?2.43, 95% CI: 1.30–4.55). Moreover, vimentin positive expression rates was significantly associated with age, tumor location, TNM stage and lymph node metastasis. However, vimentin positive expression rates did not correlate with gender, grade of differentiation, vascular invasion, the depth of invasion, hepatic metastasis or peritoneal metastasis.

Conclusions

Positive vimentin expression could serve as a poor prognostic marker in GC.  相似文献   

7.

Objectives

Long noncoding RNAs (lncRNA) are a type of noncoding RNA that comprise of longer than 200 nucleotides sequences. They can regulate chromosome structure, gene expression and play an essential role in the pathophysiology of human diseases, especially in tumorigenesis and progression. Nowadays, they are being targeted as potential biomarkers for various cancer types. And many research studies have proven that lncRNAs might bring a new era to cancer diagnosis and support treatment management. The purpose of this review was to inspect the molecular mechanism and clinical significance of long non-coding RNA- differentiation antagonizing nonprotein coding RNA(DANCR) in various types of human cancers.

Materials and methods

In this review, we summarize and figure out recent research studies concerning the expression and biological mechanisms of lncRNA-DANCR in tumour development. The related studies were obtained through a systematic search of PubMed, Embase and Cochrane Library.

Results

Long non-coding RNAs-DANCR is a valuable cancer-related lncRNA that its dysregulated expression was found in a variety of malignancies, including hepatocellular carcinoma, breast cancer, glioma, colorectal cancer, gastric cancer, and lung cancer. The aberrant expressions of DANCR have been shown to contribute to proliferation, migration and invasion of cancer cells.

Conclusions

Long non-coding RNAs-DANCR likely serves as a useful disease biomarker or therapeutic cancer target.  相似文献   

8.

Purpose

Attachment of Helicobacter pylori to the mucous epithelial cells and the mucous layer is said to be a crucial step for infection development. Sugar antigens of gastric mucins (MUC5AC, MUC1) can act as receptors for bacterial adhesins. The aim of the study was to investigate if Lotus tetragonolobus and Maackia amurensis lectins influence the level of MUC1, MUC5AC, Lewis b, H type 1, sialyl Lewis x, phospho-IκBα and interleukin 8 in Helicobacter pylori infected gastric cancer cells.

Materials and methods

The study was performed with one clinical H. pylori strain and CRL-1739 gastric cancer cells. To assess the levels of mentioned factors immunosorbent ELISA assays were used.

Results

Coculture of cells with bacteria had no clear effect on almost all examined structures. After coculture with H. pylori and lectins, a decrease of the level of both mucins, Lewis b and H type 1 antigens was observed. Lectins addition had no effect on sialyl Lewis x. Maackia amurensis caused slight increase of phospho-IκBα while interleukin 8 level was decreased.

Conclusions

Lotus tetragonolobus and Maackia amurensis lectins can mediate in binding of Helicobacter pylori to gastric epithelium.  相似文献   

9.

Background

Colorectal cancer (CRC) is one of the most common cancers worldwide. Tumor suppressor candidate 3 (TUSC3) has been reported be associated with embryogenesis and metabolism. The aim of this study is to investigate the expression of TUSC3 in CRC tissues, and to evaluate the clinical pathological characters and prognostic significance.

Method

First, we performed a bioinformatics analysis by using Oncomine and COEXPEDIA databases. Gene Set Enrichment Analysis (GSEA) was performed using TCGA data set. Then, the protein expression level of TUSC3 was detected by immunohistochemistry in 230 pairs of primary colorectal cancer and corresponding non-tumor tissues.

Result

We investigated Oncomine databases and found that TUSC3 mRNA expression was significantly higher in CRC tissues compared with normal tissues. The immunohistochemistry results demonstrated that TUSC3 was overexpressed in the CRC tissues. Furthermore, TUSC3 overexpression was associated with T stage, lymph node metastasis, and distant metastasis. TUSC3 overexpression was associated with worse overall survival for CRC, and retained significance as an independent prognostic factor for CRC. Bioinformatics analysis indicated that TUSC3 expression was associated with epithelial-mesenchymal transition signaling pathway and TUSC3 co-expression genes were obtained from COEXPEDIA.

Conclusion

TUSC3 may act as an oncogene in the progression of colorectal cancer. Moreover, TUSC3 has potential to be used as prognostic markers or therapeutic targets in CRC.  相似文献   

10.
11.

Objective

Thyroid cancer (TC) is the most common malignant endocrine-related cancer with an increasing trend worldwide. Therefore, it’s in urgent need to find new markers for prognosis and diagnosis. Many long noncoding RNAs (lncRNAs) have been reported to be aberrantly expressed in TC, and may serve as biomarkers. Therefore, we performed this meta-analysis to systematically summarize the relationship between lncRNA expressions and TC.

Methods

Sources from PubMed, Embase and Web of Science were searched. A total of 16 eligible studies including 15 on clinicopahology, 5 on prognosis and 6 on diagnosis were enrolled in our meta-analysis. Revman5.3 and Stata11.0 Software were used to conduct the meta-analysis.

Results

For diagnostic value, lncRNAs could discriminate between TC and the normal, and yield a high overall sensitivity and specificity (0.80, 95% CI: 0.75–0.84; 0.80, 95% CI: 0.70–0.87). Meanwhile, their sensitivity and specificity were 0.74 (95% CI: 0.59–0.85) and 0.81 (95% CI: 0.73–0.88) respectively, when used to differentiate patients with lymph node metastasis (LNM) from without LNM. The summary receiver operator characteristic curve (sROC) showed that lncRNAs could be considered as valuable diagnostic markers for distinguishing TC patients from the normal (AUC?=?0.84) and TC patients with LNM from TC patients without LNM (AUC?=?0.85).

Conclusions

In summary, our meta-analysis suggested that lncRNAs could function as potential diagnostic markers for TC and predict the LNM. In addition, the systematic review elaborated that lncRNAs might be as prognostic indicators in TC.  相似文献   

12.

Background

Few studies have reported the clinical and prognostic significance of C/EBP homologous protein (CHOP) in advanced gastric cancer (GC). Therefore, the present study investigated the expression of CHOP in advanced GC patients to determine its potential prognostic role.

Methods

The levels of CHOP in 95 patients with advanced GC and adjacent non-cancerous tissues were evaluated by qRT-PCR, western blot and immunohistochemistry. Furthermore, the association of CHOP expression with clinicopathological parameters and prognosis of advanced GC patients was analyzed.

Results

The levels of CHOP were down-regulated in advanced GC compared with non-cancerous tissues (P<0.01). In addition, high CHOP expression more frequently occurred in advanced GC tissues with depth of invasion of T1-2 (P?<?0.01), lower clinical stage (TNM Ⅰ-Ⅱ stage) (P<0.05) and without lymph node metastasis (P<0.05). No significant difference was observed between the expression of CHOP and age, gender, tumor size, lesion site and differentiation (P>0.05). The Kaplan-Meier survival analyses showed that the overall survival rate of advanced GC patients with positive CHOP expression was significantly higher than that of patients with negative CHOP expression (P<0.01). Univariate and multivariate Cox proportional hazards models revealed that low CHOP expression (OR?=?0.314, 95%CI: 0.176~0.794, P?=?0.003) was an independent factor for poor overall survival in advanced GC patients.

Conclusion

Low expression of CHOP predicts the poor prognosis of advanced GC patients, and CHOP may be a prognostic biomarker for patients with advanced GC.  相似文献   

13.

Objective

The aim of this study was to determine the clinicopathological significance and prognostic role of Pin1 expression and subcellular localization in colorectal cancer (CRC).

Methods

The Pin1 expression, as well as cytoplasmic and nuclear localization, was investigated using immunohistochemistry in 265 human CRC tissues. The impact of subcellular localization of Pin1 on clinicopathological significance and prognosis in CRC was evaluated.

Results

Pin1 was expressed in 164 of 265 CRCs (61.9%). Pin1 expression was not significantly correlated with any clinicopathological parameters. However, Pin1 expression was significantly correlated with worse overall and recurrence-free survivals (P?=? 0.002 and P?=? 0.001, respectively). CRCs with only nuclear Pin1 expression showed no difference in survival compared to CRCs with no Pin1 expression. Over half (51.7%, 137/265) of the CRCs had any cytoplasmic Pin1 expression, and 26.8% (71/265) had both cytoplasmic and nuclear expression. Cytoplasmic Pin1 expression was more frequent than only nuclear or no Pin1 expression in cases with vascular invasion and distant metastasis. Cytoplasmic Pin1 expression was significantly correlated with worse overall and recurrence-free survivals (P?<? 0.001 and P?<? 0.001, respectively).

Conclusion

Taken together, our results indicated different prognostic roles of subcellular Pin1expression in CRC. Cytoplasmic expression of Pin1, with or without nuclear expression, is an important factor in predicting aggressive tumor behavior and worse prognosis.  相似文献   

14.

Background

Long noncoding RNAs (lncRNAs) have been considered as significant regulators in many cancer progression, such as proliferation, invasion and other path of evolution. Nevertheless, we have not had a grasp of the role of lncRNA TP73-AS1 in gastric cancer (GC).

Methods

qRT-PCR analysis was first conducted to examine the TP73-AS1 level in both GC tissues and cell lines. Then gain or loss-of-function assays were carried out to detect the effect of TP73-AS1 on GC development. In mechanism, bioinformatics analysis and luciferase reporter assays were used to search and confirm the target gene of TP73-AS1. Finally, rescue assays were performed to confirm the influence of TP73-AS1-miR-194-5p-SDAD1 axis on GC development.

Results

TP73-AS1 was upregulated in GC tissues and cell lines. Furthermore, TP73-AS1 exerted oncogenic role in GC through promoting cell growth and metastasis. In addition, TP73-AS1 was certified as a ceRNA by regulating miR-194-5p/SDAD1 axis.

Conclusions

TP73-AS1 accelerates tumor progression in gastric cancer through regulating miR-194-5p/SDAD1 axis.  相似文献   

15.

Background

Previous studies indicated that miR-218 was deregulated in gastric cancer patients and correlated with tumor invasion and prognosis. The aim of this study was to clarify the effect of miR-218 on the malignant behavior of gastric cancer and its role in regulating Bmi-1/Akt signaling pathway.

Materials and methods

We used miR-218 mimic to transfect gastric cancer cell lines AGS and SGC-7901, and the overexpression efficiency was validated using qRT-PCR assay. MTT assay and Transwell chamber system were performed to detect the effect of miR-218 on cell proliferation, invasion and migration on gastric cancer. Western blot and qRT-PCR assay was used to test the role of miR-218 in regulating Bmi-1/Akt signaling pathway.

Results

As shown in our research, ectopic expression of miR-218 in gastric cancer cells inhibits the proliferation, invasion and migration of gastric cancer cells. In addition, miR-218 re-expression inhibits the expression of Bmi-1 and its downstream target p-Akt473, as well as MMPs and EMT process.

Conclusions

miR-218 inhibits the proliferation, invasion and migration of gastric cancer cells through modulating EMT process and the expression of MMPs via Bmi-1/Akt signaling pathway.  相似文献   

16.

Background

Aberrations in Wnt signaling pathway are related to the pathogenesis of head and neck carcinomas and their activation frequently results from epigenetic alterations. This study aimed to assess the frequency of the methylation of DAB2, which acts as a negative regulator of Wnt signaling, and correlate it with clinicopathological features in a group of oral cancer patients.

Material and methods

Forty nine patients with primary oral squamous cell carcinoma were enrolled in the study. DNA samples were isolated from surgical sections using phenol-chloroform extraction. Methylation-specific PCR was used to detect gene promoter methylation.

Results

The analysis of the occurrence of DAB2 promoter methylation in primary oral carcinomas indicated that the gene is methylated in 70% of cases. However, no correlation was found between its methylation and TNM staging or overall survival.

Conclusions

Our findings corroborate that DAB2 is a frequent target of epigenetic silencing in oral carcinomas and may be potentially used for tumor detection.  相似文献   

17.
18.

Background

We studied the expression of some major proteins involved in cell-cycle regulation and DNA repair, the roles of which are not well known in pancreatic ductal adenocarcinoma (PDAC), but which have a significant impact on carcinogenesis of many other cancers.

Methods

We immunohistochemically assessed expression levels of the cell-cycle regulators Rb1, p16 and cyclin-dependent kinase 4 (CDK4), and the DNA repair enzymes O6-methylguanine-DNA-alkyltransferase (MGMT) and flap endonuclease-1 (FEN1) separately in malignant tissue and benign tissue from resection margins in 102 cases of PDAC. Nearly all (95.1%) patients had undergone pancreaticoduodenectomy.

Results

The studied proteins showed wide but somewhat variable expression in both benign and malignant pancreatic tissues. Strong CDK4 expression in islets of Langerhans predicted poor relapse-free survival (RFS) (HR 2.874; 95% CI 1.261–6.550; p?=?.012) and within T3–4 tumors CDK4 expression in adenocarcinoma cells also predicted poor disease-free survival (DFS) (RR 2.148; 95% CI 1.081–4.272; p?=?.029). Strong MGMT expression was associated in N1 patients with weak local relapse-free survival (RFS), DFS and overall survival; all significantly in Cox regression analysis. FEN1 was also an independent predictor of decreased DFS (in the whole study population) and worse RFS (in the patients with T3–4 tumors).

Conclusions

Major cell-cycle regulator also have predictive significance, but further studies are required to evaluate this.  相似文献   

19.

Background and aim

Nucleolar and spindle-associated protein 1 (NUSAP1) is an indispensable mitotic regulator. Aberrant NUSAP1 expression is associated with perturbed mitosis and tumorigenesis. In this study, we investigated the clinical significance of NUSAP1 expression in colon cancer.

Methods and materials

Immunohistochemical staining was performed to determine NUSAP1 protein levels in paraffin colon tumor specimens. Real-time fluorescent quantitative polymerase chain reaction (RT-qPCR) was conducted to detect NUSAP1 mRNA levels in colon tumor samples. The association between NUSAP1 protein expression and clinicopathological characteristics of patients with colon cancer was assessed. A Kaplan-Meier analysis was performed to determine the prognostic significance of NUSAP1 in colon cancer. A Cox proportional hazards model was used to calculate univariate and multivariate hazard ratios for the NUSAP1 and other clinicopathological variables.

Result

NUSAP1 protein and mRNA levels were significantly higher in colon tumor tissues than in paired non-cancerous adjacent tissues (P?<?0.001, respectively). NUSAP1 protein expression was significantly correlated with histopathological grading (P?<?0.001), depth of invasion (P?=?0.001), lymph node metastasis (P?<?0.001) and TNM stage (P?<?0.001). The overall survival rate of patients with high NUSAP1 expression was significantly lower than for patients with low NUSAP1 expression (log-rank test, P?<?0.001). A multivariate Cox model demonstrated that NUSAP1 is an independent risk factor for overall survival (P?=?0.025).

Conclusion

NUSAP1 is overexpressed in colon cancer and high expression of NUSAP1 acts as an independent predictive factor for poor prognosis in colon cancer.  相似文献   

20.

Introduction

One of the most common sites of distant metastasization of prostate cancer is bone, but to date reliable biomarkers able to predict the risk and timing of bone metastasization are still lacking.

Patients and methods

Surgically resected paraffin embedded samples from 12 primary prostate cancers that developed metachronous bone metastasis at different time points were studied (six cases within 2 years, six cases after 5 years from surgery). A targeted next-generation DNA and RNA sequencing able to assess simultaneously mutations, copy number alterations and fusion events of multiple genes was used. Immunohistochemistry was used to assess mTOR pathway activation.

Results

Rearrangements of ETS family genes, molecular alterations in PTEN and TP53 genes were detected in 10, 6 and 5 cancers, respectively. Nine samples showed TMPRSS2-ERG fusions, which were associated with increased ERG expression at immunohistochemistry. mTOR pathway activation was documented in 6 patients, with a clear trend of prevalence in late-metastatic patients (p?=?0.08).

Conclusions

A simultaneous next-generation targeted DNA and RNA sequencing is applicable on routine formalin-fixed paraffin-embedded tissues to assess the multigene molecular asset of individual prostate cancers. This approach, coupled with immunohistochemistry for ERG and mTOR pathway proteins, may help to better characterize prostate cancer molecular features with a potential impact on clinical decisions.  相似文献   

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