Deregulated HOXB7 expression predicts poor prognosis of patients with malignancies of digestive system.

INTRODUCTION: Numerous studies have investigated the relationship between deregulated HOXB7 expression with the clinical outcome in patients with digestive stem cancers, HOXB7 has showed negative impacts but with varying levels. We aimed to comprehensively evaluate the prediction and prognostic value of HOXB7 in digestive stem cancers. EVIDENCE ACQUISITION: Electronic databases updated to December 1st, 2016 were retrieved to collect relevant eligible studies to quantitatively explore the potential roles of HOXB7 as a prognostic indicator in digestive system cancers. EVIDENCE SYNTHESIS: A total of 9 studies (N.=1298) was included in this synthetical meta-analysis. The pooled hazard ratios suggested that high expression of HOXB7 protein was associated with poor prognosis of OS in patients with digestive system cancers (HR=1.97, 95% CI: 1.65-2.28, P=0.000), and HOXB7 protein could act as an independent prognostic factor for predicting OS of patients with digestive system cancers (HR=2.02, 95% CI: 1.69-2.36, P=0.000). Statistical significance was also observed in subgroup meta-analysis based on the cancer type, histology type, country, sample size and publication date. Furthermore, we examined the correlations between HOXB7 protein and clinicopathological features. It showed that altered expression of HOXB7 protein was correlated with tumor invasion (P=0.000), lymph node status (P=0.000), distant metastasis (P=0.001) and TNM stage (P=0.000). However, the expression of HOXB7 protein was not associated with age (P=0.64), gender (P=0.40) or levels of differentiation (P=0.19). CONCLUSIONS: High expression of HOXB7 protein was associated with poor prognosis of patients with digestive system cancers, as well as clinicopathologic characteristics, including the tumor invasion, lymph node status, distant metastasis and TNM stage. The expression of HOXB7 protein was not associated with age, gender or levels of differentiation. HOXB7 protein expression level in tumor tissue might serve as a novel prognostic marker for digestive system cancers.

Low Expression of LncRNA Cancer Susceptibility Candidate 2 and its Clinical Significance in Cancer Tissues.

BACKGROUND/AIMS: Long noncoding RNA (lncRNA) cancer susceptibility candidate 2 (CASC2) is downregulated in various cancers and involved in both tumorigenesis and progression. The aim of this study was to assess the prognostic value of lncRNA CASC2 in cancer patients. METHODS: We searched the Web of Science, PubMed, EMBASE, China National Knowledge Infrastructure (CNKI), and the Wanfang database to identify studies evaluating the prognostic value of lncRNA CASC2 in cancer patients. Pooled hazard ratios (HRs) or odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using fixed-effects/random-effects models. RESULTS: A total of eight studies were included. The combined results showed that lncRNA CASC2 was significantly associated with decreased overall survival (OS) (HR = 0.37, 95% CI, 0.27-0.46, P < 0.001). Subgroup analyses further indicated that low expression of lncRNA CASC2 predicted decreased OS in cancer patients. Additionally, low CASC2 expression levels in cancer tissues appeared to be correlated with advanced clinical staging (OR = 3.32, 95% CI, 2.29-4.80, P < 0.001). CONCLUSIONS: Low CASC2 expression appears to be predictive of poor OS and advanced tumor stage in multiple cancers. CASC2 expression may serve as unfavorable prognostic factor for clinical outcomes in cancer patients.

The association of plasma fibrinogen with clinicopathological features and prognosis in esophageal cancer patients.

BACKGROUND: Numerous studies have shown that plasma fibrinogen was linked to esophageal cancer (EC) risk. However, the clinical significance of plasma fibrinogen in EC patients remain unclear and need to be further clarified. RESULTS: A total of 2865 patients with EC from 11 published studies were included in this meta-analysis. The prognostic and clinical relevance of plasma fibrinogen were evaluated in EC patients. Statistical significance of the pooled hazard ratio (HR) was found for overall survival (OS), disease free survival (DFS) and recurrence-free survival (RFS) in EC. Subgroup analyses for OS were also performed to confirm the prognostic value of plasma fibrinogen. Additionally, the overall results indicated that elevated plasma fibrinogen was significantly associated with tumor invasion, lymph node metastasis (LNM) and clinical stage. MATERIALS AND METHODS: A comprehensive literature retrieval was performed in PubMed, Embase, Cochrane database, Web of science and Chinese National Knowledge Infrastructure (CNKI) and Wanfang databases to identify relevant studies published prior to April 15, 2017. CONCLUSIONS: Elevated plasma fibrinogen could be served as a promising biomarker for predicting a poor prognosis and unfavorable clinicopathologic features for EC.

Prognostic value of Flotillin-1 expression in patients with solid tumors.

BACKGROUND: In numerous studies, Flotillin-1 was reported to be involved in tumor progression, indicating prognosis in various types of cancer. However, the results were inconsistent. RESULTS: A total of 2473 patients from 13 articles were included. The results indicated that: (1) Patients detected with high expression level of Flotillin-1 protein had a significantly shorter OS (HR =1.64; 95%CI: 1.39-1.88), statistical significance was also observed in subgroup meta-analyses stratified by the cancer type, nationality, detecting method, cutoff value, analysis type, sample size and publication date. (2) Patients with high Flotillin-1 protein expression level had a poorer DFS (HR = 2.49; 95%CI: 1.64-3.35), a worse RFS(HR = 3.26; 95%CI: 1.10-5.43) and a potential shorter PFS(HR = 1.84; 95%CI: 0.81-2.87). (3) The pooled odds ratios (ORs) showed that increased Flotillin-1 level was also related to lymph node metastasis (OR =6.30; 95% CI: 3.15-12.59), distant metastasis (OR =6.02; 95% CI: 1.50-24.06) and more advanced TNM stage (OR =4.69; 95% CI: 2.74-8.03). MATERIALS AND METHODS: A comprehensive retrieval was performed in multiple databases, including PubMed, Embase, Web of Science and CNKI. The relevant articles were screened for investigating the association between increased Flotillin-1 expression level and prognosis. Additionally, clinicopathological features data was also extracted from these studies. CONCLUSIONS: High expression level of Flotillin-1 protein was correlated with poorer clinical outcome. It might serve as a prognostic biomarker and a potential predictive factor of clinicopathology in various tumors. Further well-designed clinical studies should be performed to verify the clinical utility of Flotillin-1 in human solid tumors.

The prognostic significance of UCA1 for predicting clinical outcome in patients with digestive system malignancies.

BACKGROUND: Urothelial Carcinoma Associated 1 (UCA1) was an originally identified lncRNA in bladder cancer. Previous studies have reported that UCA1 played a significant role in various types of cancer. This study aimed to clarify the prognostic value of UCA1 in digestive system cancers. RESULTS: The meta-analysis of 15 studies were included, comprising 1441 patients with digestive system cancers. The pooled results of 14 studies indicated that high expression of UCA1 was significantly associated with poorer OS in patients with digestive system cancers (HR: 1.89, 95 % CI: 1.52-2.26). In addition, UCA1 could be as an independent prognostic factor for predicting OS of patients (HR: 1.85, 95 % CI: 1.45-2.25). The pooled results of 3 studies indicated a significant association between UCA1 and DFS in patients with digestive system cancers (HR = 2.50; 95 % CI = 1.30-3.69). Statistical significance was also observed in subgroup meta-analysis. Furthermore, the clinicopathological values of UCA1 were discussed in esophageal cancer, colorectal cancer and pancreatic cancer. MATERIALS AND METHODS: A comprehensive retrieval was performed to search studies evaluating the prognostic value of UCA1 in digestive system cancers. Many databases were involved, including PubMed, Web of Science, Embase and Chinese National Knowledge Infrastructure and Wanfang database. Quantitative meta-analysis was performed with standard statistical methods and the prognostic significance of UCA1 in digestive system cancers was qualified. CONCLUSIONS: Elevated level of UCA1 indicated the poor clinical outcome for patients with digestive system cancers. It may serve as a new biomarker related to prognosis in digestive system cancers.

Prognostic and clinicopathological significance of long noncoding RNA H19 overexpression in human solid tumors: evidence from a meta-analysis.

BACKGROUND: Many studies have reported that the expression level of lncRNA H19 was increased in various tumors. LncRNA H19 may play a significant role in cancer occurrence and development. An increased level of H19 was also associated with poor clinical outcomes of cancer patients. RESULTS: 12 eligible studies were screened, with a total of 1437 cancer patients. From the results of meta-analysis, as for prognosis, the patients with high expression of lncRNA H19 were shorter in OS (HR=1.08, 95% CI: 1.05-1.12). Statistical significance was also showed in subgroup meta-analysis stratified by the cancer type, analysis type and sample size. In addition, the patients detected with high H19 expression may be poorer in DFS (HR=1.27; 95% CI = 0.97-1.56). As for clinicopathology, it showed that increased H19 was related to poor histological grades (OR=2.31, 95% CI: 1.12-4.75), positive lymph node metastasis (OR=2.29, 95 % CI: 1.21-4.34) and advanced clinical stage (OR=4.83, 95% CI: 3.16-7.39). MATERIALS AND METHODS: Eligible studies were collected by retrieving keywords in PubMed, Web of Science, Embase, CNKI and Wanfang database, from 1966 to April 23, 2016. This quantitative meta-analysis was performed with Stata SE12.0 and RevMan5.3 software. It aimed to explore the association between H19 expression level and prognosis and clinicopathology. CONCLUSIONS: LncRNA-H19 may be a novel molecular marker for predicting solid tumors. It can also be a predictive factor of clinicopathological features in various cancers. Further studies are needed to verify the clinical utility of H19 in human cancers.

Association of the HOTAIR rs4759314 polymorphism with cancer risk: a meta-analysis.

PURPOSE: To explore the association between HOTAIR rs4759314 and cancer risk. METHODS: A comprehensive online search was conducted using PubMed, EMBASE, and CNKI databases to identify relevant studies. The case-control studies related to HOTAIR rs4759314 polymorphism and cancer risk were selected according to the inclusion and exclusion criteria. The retrieval time was until November 2015. After extracting the basic data information and performing an evaluation of the quality of the literature, the meta-analysis was performed using STATA 12.0 software, by calculating the odds ratio (OD) and 95% confidence interval (95% CI), and further subgroup analysis, literature publication bias testing, and sensitivity analysis. RESULTS: The studies included a total of 5025 patients with cancer and 5657 controls. The results found no significant association between the HOTAIR rs4759314 polymorphism and cancer risk in a Chinese population (G vs A, OR=1.06, 95% CI :0.87-1.30 ; GG/GA vs AA, OR=1.07, 95% CI: 0.87-1.32; GG vs GA/AA, OR=0.75, 95% CI:0.39-1.43; GA vs AA, OR=1.08, 95% CI: 0.88-1.33; GG vs AA, OR=0.76, 95% CI:0.39-1.45) (all p<0.05). However, A allelic gene was associated with lower risk of gastric cancer, while G allelic gene may act as a genetic susceptibility factor for gastric cancer in Chinese population. CONCLUSION: No significant association was noted between the HOTAIR rs4759314 polymorphism and cancer risk in a Chinese population.

Prognostic value of long non-coding RNA UCA1 in human solid tumors.

BACKGROUND: Numerous studies have shown that the expression of UCA1 was aberrantly upregulated in various cancer types. High expression of UCA1 was reported to be associated with unfavorable prognosis in cancer patients. RESULTS: A total of 1240 patients from 15 articles were included. The results indicated that a significantly shorter OS was observed in patients with high expression level of UCA1 (HR = 1.71, 95% CI: 1.43-1.99), in the subgroup analysis, the association was also observed in patients with cancers of digestive system (HR = 2.12, 95% CI: 1.59-2.66). Statistical significance was also observed in subgroup meta-analysis stratified by the cancer type, cut-off value, analysis type and sample size. Furthermore, poorer DFS was observed in patients with high expression level of UCA1 (HR = 2.54; 95% CI: 1.09-4.00). Additionally, the pooled odds ratios (ORs) showed that increased UCA1 was also related to positive lymph node metastasis (OR = 2.98, 95% CI: 2.06-4.30), distant metastasis (OR = 3.14, 95% CI: 1.77-5.58) and poor clinical stage (OR = 2.76, 95% CI: 2.08-3.68). MATERIALS AND METHODS: A comprehensive retrieval was conducted in multiple databases, including PubMed, Embase, Web of Science and CNKI. We collected relevant articles to explore the association between the expression levels of UCA1 and prognosis. CONCLUSIONS: High expression level of UCA1 was associated with poor clinical outcome. UCA1 could serve as a novel biomarker for prognosis and might be a potential predictive factor for clinicopathological characteristics in various cancers. Further studies should be performed to verify the clinical utility of UCA1 in human solid tumors.

Long noncoding RNA AFAP1-AS1, a potential novel biomarker to predict the clinical outcome of cancer patients: a meta-analysis.

A number of studies have demonstrated that the expression level of actin filament-associated protein 1 antisense RNA 1 (AFAP1-AS1) was upregulated in various cancers. High expression of AFAP1-AS1 is associated with an increased risk of metastasis and a poor prognosis in cancer patients. The electronic search was conducted in PubMed, EMBASE, Cochrane Library, China National Knowledge Infrastructure, and Wanfang database. We collected relevant articles to explore the association between the expression levels of AFAP1-AS1 and lymph node metastasis, distant metastasis, overall survival, relapse-free survival, and progression-free survival. A total of 1,017 patients from eight studies were finally included. The results showed that cancer patients with high AFAP1-AS1 expression suffered an increased risk of developing lymph node metastasis (odds ratio =3.19, 95% confidence interval [CI]: 2.11-4.83, P<0.00001) and distant metastasis (odds ratio =3.05, 95% CI: 1.84-5.04, P<0.0001). Moreover, we found that patients with high AFAP1-AS1 expression also had a poorer overall survival (hazard ratio [HR]: 1.98, 95% CI: 1.57-2.38, P=0.000), a worse progression-free survival (HR: 1.73, 95% CI: 1.11-2.35, P=0.000), and a shorter recurrence-free survival (HR: 1.96, 95% CI: 1.02-2.90, P=0.000) than those with low AFAP1-AS1 expression. High expression of AFAP1-AS1 was associated with poor clinical outcome. AFAP1-AS1 might serve as a potential novel biomarker for indicating the clinical outcomes in human cancers.

HOXB7 as a promising molecular marker for metastasis in cancers: a meta-analysis.

Numerous studies on carcinoma have revealed that the expression level of HOXB7 in cancerous tissues was significantly higher than that in noncancerous tissues. Elevated expression of HOXB7 is associated with the susceptibility to lymph node metastasis and distant metastasis in various tumors. In this study, a meta-analysis was performed to involve majority of relevant articles and explore the association of HOXB7 expression level with metastasis in cancer patients. Literature retrieval was conducted by searching in a number of electronic databases (up to December 1, 2015). The meta-analysis was conducted with RevMan 5.3 software and Stata SE12.0. A total of 1,532 patients with carcinoma from 14 studies were included in analysis. The results of meta-analysis demonstrated that lymph node metastasis was observed more frequently in the patients group with high expression level of HOXB7 than in the patients group with low expression level of HOXB7 (odds ratio =2.17, 95% CI: 1.74-2.71, P<0.00001, fixed-effects model). In addition, a similar result was observed in the association between HOXB7 expression and distant metastasis; the odds ratio was 1.77 (95% CI: 1.09-2.88, P=0.02, fixed-effects model). This meta-analysis demonstrated that the overexpression of HOXB7 was significantly associated with metastasis in cancer patients, which may be served as a common molecular marker for indicating cancer metastasis.

Long noncoding RNA ANRIL: a potential novel prognostic marker in cancer: a meta-analysis.

INTRODUCTION: Numerous researches have showed that the dysregulation of lncRNA ANRIL play a significant role in cancer progression, and high expression of ANRIL may have important clinical value. This meta-analysis aims to investigate potential clinical application role of ANRIL as a biomarker for cancer prognosis. EVIDENCE ACQUISTION: The electronic search was conducted in Pubmed, EMBASE, Web of Science, CNKI and Wanfang database (up to January 27, 2016). We collected relevant articles to explore the association between the expression levels of ANRIL and overall survival (OS). EVIDENCE SYNTHESIS: A total of 519 cancer patients from six studies were finally included. The results showed that cancer patients with high ANRIL expression may have a poorer OS (HR=1.95, 95%CI:1.37-2.53, P=0.000, fixed-effect model) than those with low ANRIL expression. CONCLUSIONS: High expression of ANRIL is associated with poor clinical outcome. ANRIL might be act as a novel potential prognostic biomarker in various cancers.

Long non-coding RNA-LET can indicate metastasis and a poor prognosis: a meta-analysis.

INTRODUCTION: Recent studies have reported that long non-coding RNA low expression in tumor (lncRNA-LET) was down-regulated in several cancers. The current meta-analysis aims to determine whether lncRNA-LET can be used as a potential biomarker for metastasis and prognosis. EVIDENCE ACQUISITION: We collected all relevant papers by searching multiple electronic databases (PubMed, EMBASE, Google Scholar, CNKI, Wanfang Database) and explored the association between the expression levels of lncRNA-LET and lymph node metastasis (LNM), distant metastasis (DM) and overall survival (OS). EVIDENCE SYNTHESIS: A total of 383 patients from four studies were finally included. The meta-analysis results showed that LNM occurred more frequently in patients from the lncRNA-LET low expression group than in patients from the lncRNA-LET overexpression group (OR=4.56, 95% CI 2.92-7.12, P<0.00001), and a similar result was observed between lncRNA-LET expression and DM (OR=4.77, 95% CI 2.29-9.94, P<0.0001). Additionally, we found that patients with low expression of lncRNA-LET had a poorer OS than those with lncRNA-LET overexpression (HR=2.39, 95% CI 1.57-3.21, P=0.000). CONCLUSIONS: lncRNA-LET may serve as a common molecular marker for metastasis and prognosis in human cancers.

Positive association between IL-16 rs1131445 polymorphism and cancer risk: a meta-analysis.

INTRODUCTION: The association between IL-16 rs1131445 polymorphism and cancer risk is not consistent or even contradictory, this meta-analysis aims to investigate the role of IL-16 gene rs1131445 polymorphisms in the risk of cancer. EVIDENCE ACQUISITION: A comprehensive online search was conducted in PubMed, EMBASE and CNKI databases to identify eligible studies. The case-control studies related IL-16 rs1131445 C/T polymorphism with the cancer susceptibility were selected according to the inclusion and exclusion criteria. After extracting the basic data information and quality of literature evaluation, the meta-analysis was performed by using STATA 12.0 software, with calculating odds ratio and 95% confidence interval, and further subgroup analysis, literature publication bias test and sensitivity analysis. EVIDENCE SYNTHESIS: There are totally 1677 cases and 1989 non-tumor controls finally involved. Meta-analysis showed that there are statistical correlations between the IL-16 rs1131445 C/T polymorphism and the cancer risk in Asian populations (TS vs. C, OR=0.80, 95%CI: 0.73-0.88; TT vs. TC, OR=0.75, 95%CI: 0.65-0.87; TT vs. CC, OR=0.69, 95% CI: 0.56-0.84; CC+TC vs. TT, OR=1.36, 95%CI: 1.19-1.55; CC vs. TC+TT, OR=1.27, 95%CI: 1.05-1.53) (all P<0.05). CONCLUSIONS: IL-16 rs1131445 C/T polymorphism is related to the susceptibility to cancer in Asians, suggesting that the C allelic gene of rs1131445 is significantly associated with an increasing cancer risk.

Long Non-Coding RNA HOXA Transcript at the Distal Tip as a Putative Biomarker of Metastasis and Prognosis: a Meta-Analysis.

BACKGROUND: Many studies demonstrated that the expression level of HOTTIP in cancerous tissues was significantly higher than that in adjacent normal tissues. Increased expression of HOTTIP was associated with metastasis and a poor prognosis. METHODS: The current meta-analysis collected all relevant articles and explored the association of HOTTIP expression levels with lymph node metastasis (LNM), distant metastasis (DM), and overall survival (OS) in multiple cancers. Literature collections were conducted by searching a number of electronic databases (up to December 31, 2015). The Meta-analysis was conducted using RevMan5.3 software and Stata SE12.0. RESULTS: A total of 602 patients with cancer from seven studies were included. The Meta-analysis results showed that lymph node metastasis occurred more frequently in patients with high HOTTIP expression than in patients with low HOTTIP expression (OR = 2.22, 95% CI: 1.47 - 3.37, p = 0.0002, fixed-effects model), and a similar result was observed between HOTTIP expression and distant metastasis (OR = 3.30 (95% CI: 1.78 - 6.12, p = 0.0001, fixed-effects model). Moreover, we found that cancer patients with high HOTTIP expression had a poorer overall survival than those with low HOTTIP expression (HR = 2.23, 95% CI: 1.64 - 2.83, p = 0.000, fixed-effects model). CONCLUSIONS: HOTTIP may serve as an independent biomarker for predicting the clinical outcome of cancer patients.