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1.

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   

2.
3.

Objective

To evaluate the expression and prognostic significance of ALDH1A1 in gastric neuroendocrine carcinoma.

Materials and methods

Immunohistochemical stains of ALDH1A1 were evaluated in 67 cases of gastric neuroendocrine carcinoma. The findings were correlated with clinicopathologic variables and overall survival.

Results

Immunohistochemistry revealed positive cytoplasmic immunoreactivity in 35 of 67 (52.2%) tumors and strongly positive immunoreactivity in 14 of 67 (20.9%). Strongly positive ALDH1A1 expression, but not positive staining, was significantly associated with lymph node status, lymphovascular invasion, and ki-67 index (P = 0.039, 0.045, and 0.045, respectively). Kaplan‐Meier survival curves and log-rank tests showed significantly poorer prognoses in cases of high ALDH1A1 expression compared to cases of low ALDH1A1 expression or the negative control group (MST, 17 vs. 52 months; P = 0.026). Multivariate analysis showed that high ALDH1A1 expression, lymph node metastasis, and lymphovascular invasion had significant associations with decreased overall survival (P = 0.029, 0.008, and 0.005, respectively).

Conclusions

High ALDH1A1 expression may be a prognostic indicator of survival in patients with gastric neuroendocrine carcinoma.  相似文献   

4.

Background

Expression of VEGFRs may affect cancer prognosis. The aim of this work is to evaluate the prognostic significance of VEGFRs of patients with gastric cancer.

Methods

The databases PubMed, Embase, Web of Science, and Cochrane Library as well as ASCO and ESMO were searched systematically for articles reporting the prognostic significance of tissue VEGFRs in gastric cancer. The statistical analyses were carried out using Stata version 12.0.

Results

A total of 8 articles comprising 950 patients were eligible for meta-analysis. The combined HR of studies evaluating total VEGFRs overexpression was 1.42 (95% CI 1.01-2.00, P?=?0.044), suggesting that it had prognosis significance in overall survival of gastric cancer. Subgroup analysis showed that it was VEGFR-2 (HR 1.81, 95% CI 1.31–2.49, P?<?0.001) but not VEGFR-3 (HR 0.91, 95% CI 0.45–1.82, P?=?0.787) overexpression was associated with an increased risk of median overall survival (mOS) and it can be a potentially predictive biomarker for gastric cancer.

Conclusions

VEGFR-2 overexpression is a promising negative prognosis predictor for patients with gastric cancer. The prognosis significance of VEGFR-3 still need further study.  相似文献   

5.
6.
7.

Background

It was found that G-protein-coupled receptor kinase 3 (GRK3) played key biological roles in some cancers. However, its associations with clinicopathologic features and prognosis in pancreatic ductal adenocarcinoma (PDAC) remain unknown.

Methods and methods

Expression of GRK3 was detected, using tissue microarray-based immunohistochemistry, in paired formalin-fixed paraffin-embedded tumor and non-tumor samples from 165 patients with PDAC after curative resection, and was further correlated with clinicopathologic parameters and cancer-specific survival (CSS).

Results

It was shown that GRK3 expression was much lower in tumor than in non-tumor tissues. Moreover, expression of GRK3 in tumor tissues was significantly associated with gender and T stage. Univariately, high GRK3 expression was predictive for favorable CSS, along with some conventional clinicopathologic variables. In multivariate Cox regression test, GRK3 expression remained to be a significant prognostic marker for PDAC. Finally, combination of GRK3 with some clinicopathologic variables, especially N stage, obtained more precise prediction for CSS.

Conclusions

Our data suggested that expression of GRK3 was down-regulated in PDAC and was an independent prognostic factor.  相似文献   

8.

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   

9.

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   

10.

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   

11.

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   

12.

Background

Breast cancer is one of the most common malignancies worldwide. However, the detailed molecular mechanisms underlying breast cancer metastasis are still incompletely clear. MicroRNAs (miRNAs) play a crucial role in cancer metastasis. In this study, we aimed to analyze the expression and function of miR-449a in breast cancer.

Material and methods

A total of 15 human primary breast cancer tissues and adjacent non-cancerous tissues (10 pairs) were obtained. MiR-449a was examined in tumor tissues and adjacent nontumorous tissues of breast cancer patients and cell lines by real-time PCR. The protein expression levels were analyzed by western blot and immunohistochemistry staining. Luciferase reporter assays was used to validate the target of miR-449a. The effect of miR-449a on breast cancer cell migration and invasion were studied in vitro and in vivo.

Results

The expression levels of miR-449a were significantly decreased in breast cancer tissues and cell lines. Overexpression of miR-449a suppressed breast cancer cell proliferation, clone formation, migration, invasion and metastasis in vitro and in vivo. Pleomorphic adenoma gene like-2 (PLAGL2) was identified as a major target of miR-449a. Both overexpression of miR-449a inhibited the expression of PLAGL2 significantly and the knockdown of PLAGL2 expression inhibited the breast cancer cell proliferation and metastasis.

Conclusion

We demonstrate the miR-449a tumor suppressor role in breast cancer cell migration and invasion via targeting PLAGL2. These findings suggesting that miR-449a/PLAGL2 could serve as a therapeutic strategy for targeting breast cancer.  相似文献   

13.

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   

14.

Introduction

Deplastination is a process that reverses plastination. While the process is in its infancy, this study was designed to see if deplastinated tissues can be used for histopathological studies.

Methods

In this study, a slice of liver tissue was split into two parts. The first half was processed, sectioned and stained with routine H&E staining while the other half was plastinated with S10 plastination technique and was deplastinated after 3 months using sodium methoxide as the deplastinating agent. It was latter stained with routine H&E. The slides were assessed qualitatively on parameters like tissue and cell identification, staining property, preservation of tissue architecture, visualisation of intracellular structures like nuclei, nucleoli, fat goblets etc. and presence of artefacts due to the process.

Results

Identification of tissue was possible on the deplastinated slides. Intracellular structures like nuclei, nucleoli, fat droplets were identified in the deplastinated slides.

Discussion

In this study, we have found that sodium methoxide and methanol form good deplastinating agents for small sections of tissue. Identification of endpoint of deplastination forms a crucial step in the process.  相似文献   

15.

Objectives

Recent studies suggest that the interaction between interleukin (IL)-1β and IL-6 in the microenvironment might be involved in the development and progression of human colorectal cancer (CRC). However, the expression of IL-1β/IL-6 network within the CRC microenvironment is not fully understood.

Materials and methods

The level of IL-1β/IL-6 network expression in 40 biopsies of sporadic CRC and 15 biopsies of controls was assessed using quantitative real-time polymerase chain reaction (PCR) assay, immunohistochemistry (IHC) and double immunofluorescence staining.

Results

Quantitative results obtained by real-time PCR revealed that both IL-1β and IL-6 mRNA expressions were increased in CRC tissues compared with expressions in controls. In which, IL-6 mRNA expression in primary CRC tissues showed a statistically significant relationship with tumor invasion depth. IHC observations confirmed that increased expression of IL-1β and IL-6 immunoreactivities was located in both the CRC epithelium and stroma. Furthermore, IHC results also revealed that increased expression of IL-1β receptor type 1 (IL-1R1) and IL-6 receptor (IL-6R) were observed in both CRC epithelial and stromal cells. IHCs in serial CRC sections and double immunofluorescence staining revealed a highly co-expression of IL-1R1 immunoreactivity with IL-6 immunoreactivity in the same cells, which confirmed a histological fundament of IL-1β/IL-6 network.

Conclusion

The IL-1β/IL-6 network is highly expressed in the CRC microenvironment, indicating that this network is important in the progression of CRC.  相似文献   

16.

Background and aim

Recent studies of several carcinomas have reported that aquaporin possesses novel oncogenic properties. The aim of this study was to clarify the involvement of aquaporin-1 and ?5 in the proliferation, invasion and metastasis of soft tissue sarcomas.

Materials and methods

The expression of aquaporin-1 and -5 was immunohistochemically examined in 73 soft tissue sarcomas as well as in benign, locally aggressive soft tissue tumors, and in soft tissues of adult humans and human fetuses. The mRNA and protein expression of aquaporin-1 and -5 genes were quantified in 19 sarcoma tissues.

Results

Aquaporin-1 was expressed in the tumor cells of 37 (51%) and aquaporin-5 in 29 (40%) of 73 soft tissue sarcomas. Two expression patterns were identified: a differentiation-dependent pattern, similar to their expression in adult human soft tissue and in benign soft tissue tumors, and an aggressiveness-related pattern, that is similar to their expression in the mesenchymal cells of the developing fetal limb. The latter expression pattern proved to be an independent prognostic factor for patients with soft tissue sarcoma, in which aquaporin-1 was related to the invasiveness, and aquaporin-5 to the proliferation of soft tissue sarcoma cells.

Conclusion

These results indicate pivotal roles for aquaporin-1 and -5 in the aggressive growth and metastatic potential of soft tissue sarcomas, suggesting that they are promising targets for the treatment of patients with intractable soft tissue sarcoma.  相似文献   

17.

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   

18.

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   

19.

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   

20.

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   

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