Csf1r mediates enhancement of intestinal tumorigenesis caused by inactivation of Mir34a.

The CSF1 receptor (CSF1R) encoding mRNA represents a direct target of miR-34a. However, the in vivo relevance of the suppression of CSF1R by miR-34a for intestinal tumor suppression mediated by the p53/miR-34a pathway has remained unknown. Here, Apc Min/+ mice with intestinal-epithelial cell (IEC)-specific deletions of Mir34a showed increased formation of adenomas and decreased survival, whereas deletion of Csf1r decreased adenoma formation and increased survival. In adenomas deletion of Mir34a enhanced proliferation, STAT3 signaling, infiltration with fibroblasts, immune cells and microbes, and tumor stem cell abundance and decreased apoptosis. Deletion of Csf1r had the opposite effects. In addition, homeostasis of intestinal secretory and stem cells, and tumoroid formation were affected in opposite directions by deletion of Mir34a and CSF1R. Concomitant deletion of Csf1r and Mir34a neutralized the effects of the single deletions. mRNAs containing Mir34a seed-matching sites, which encode proteins related to EMT (epithelial-mesenchymal transition), stemness and Wnt signaling, were enriched after Mir34a inactivation in adenomas and derived tumoroids. Netrin-1/Ntn1 and Transgelin/Tagln were characterized as direct targets of Mir34a and Csf1r signaling. Mir34a-inactivation related expression signatures were associated with CMS4/CRISB+D, stage 4 CRCs and poor patient survival. In tumoroids the loss of Mir34a conferred resistance to 5-FU which was mediated by Csf1r. This study provides genetic evidence for a requirement of Mir34a-mediated Csf1r suppression for intestinal stem/secretory cell homeostasis and tumor suppression, and suggests that therapeutic targeting of CSF1R may be effective for the treatment of CRCs with defects in the p53/miR-34a pathway.

CC Chemokine Receptors in Lung Adenocarcinoma: The Inflammation-Related Prognostic Biomarkers and Immunotherapeutic Targets.

BACKGROUND: Lung adenocarcinoma (LUAD) is the most common type of lung cancer with a high incidence and increased mortality. CC chemokine receptors were participating in the modulation of the tumor microenvironment and involved in carcinogenesis and tumor development. However, the potential mechanistic values of CC chemokine receptors as clinical biomarkers and therapeutic targets in LUAD have not been fully clarified. METHODOLOGY: ONCOMINE, UALCAN, GEPIA, Kaplan-Meier Plotter, SurvExpress, MethSurv, SurvivalMeth, cBioPortal, String, GeneMANIA, DAVID, Metascape, TRRUST, LinkedOmics, and Timer were applied in this work. RESULTS: The transcriptional levels of CCR1/10 in LUAD tissues were significantly reduced while the transcriptional levels of CCR3/6/7/8 were significantly elevated, and the expression of CCR1 was the highest in LUAD among these CC chemokine receptors. A significant correlation was found between the expression of CCR2/4/6/7 and the pathological stage of LUAD patients. There were significant associations between CCR2/3/4/5/6/10 expression levels and OS in LUAD, and LUAD patients with high transcriptional levels of CCR3/4 had inferior first-progression survival. In addition, the prognostic values of CC chemokine receptors signature in LUAD were explored in three independent cohorts, the high-risk group displayed unfavorable OS compared with the low-risk group, and the LUAD cases in the high-risk group also suffered inferior RFS than that in the low-risk group. And for the prognostic value of the DNA methylation of CC chemokine receptors, we found 1 CpG of CCR2, 2 CpGs of CCR3, 1 CpG of CCR4, 3 CpGs of CCR6, 3 CpGs of CCR7, 1 CpG of CCR8, and 3 CpGs of CCR9 were significantly associated with prognosis in LUAD patients. However, the DNA methylation signature analysis showed there was no statistically significant association between the high- and low-risk group. For potential mechanism, the neighbor gene networks, interaction analyses, functional enrichment analyses of CC chemokine receptors in LUAD were performed, the transcription factor targets, kinase targets, and miRNA targets of CC chemokine receptors were also identified in LUAD. We also found significant correlations among CC chemokine receptors expression and the infiltration of immune cells, the tumor infiltration levels among LUAD with different somatic copy number alterations of these chemokine receptors were also assessed. Moreover, the Cox proportional hazard model showed that CCR1/2/10, B_cell, CD4_Tcell were significantly related to the clinical outcome of LUAD patients. CONCLUSION: CC chemokine receptors might serve as immunotherapeutic targets and prognostic biomarkers in LUAD.

Identification of Prognostic Biomarkers and Molecular Targets Among JAK Family in Breast Cancer.

BACKGROUND: Janus kinases (JAKs) are a family of non-receptor tyrosine kinases involved in multiple malignancies. However, clinical values of JAKs as prognostic markers and potential mechanism as molecular targets in breast invasive carcinoma (BC) are not completely clarified. METHODOLOGY: TIMER, UALCAN and GEPIA were used to assess the expression and methylation levels of JAKs in BC. Kaplan-Meier Plotter, bc-GenExMiner, SurvExpress, TRGAted, MethSurv, and SurvivalMeth were used to assess the multilevel prognostic significance of JAKs in breast cancer patients. And cBioPortal, TIMER, STRING, GeneMANIA, NetworkAnalysis, LinkedOmics, DAVID 6.8, and Metascape were applied for multilayer networks and functional enrichment analyses. Correlations between immune cell infiltrates/their gene markers and JAKs were evaluated by TIMER. RESULTS: We first explored the expression and methylation level of JAKs in breast cancer and found significantly reduced JAK1 and JAK2 expression at mRNA and protein levels, significantly higher JAK3 protein expression, and significantly increased TYK2 expression at mRNA level but decreased at protein level. In addition, hypermethylation of JAK3 and TYK2 and hypomethylation of JAK1 were found in tumor samples. In terms of prognostic values of JAKs in BC patients, low transcriptional levels of JAK1, JAK2, JAK3, and TYK2 indicated worse OS/DMFS/PPS/RFS/DFS, inferior DFS, worse RFS, and shorter OS/DMFS/RFS, respectively. The mRNA signature analysis showed that high-risk group had unfavorable OS/RFS/MFS. Low JAK2 protein level indicated unfavorable DSS/PFS in BC patients. Five CpGs of JAK1, four CpGs of JAK2, 20 CpGs of JAK3, and 13 CpGs of TYK2 were significantly associated with prognosis in BC patients. The DNA methylation signature analysis also suggested worse prognosis in the high-risk group. For potential biological roles of JAKs, interaction analyses, functional enrichment analyses for biological process, cellular component, molecular function, and KEGG pathway analyses of JAKs and their neighbor genes in BC were conducted. Kinase targets, gene-miRNA interactions, and transcription factor-gene interactions of JAKs were also identified. Furthermore, JAKs were found to be significantly related to immune infiltrates as well as the expression levels of multiple immune markers in BC. CONCLUSION: JAKs showed multilevel prognostic value and important biological roles in BC. They might serve as promising prognostic markers and possible targets in breast cancer.

Prognostic Value of Gastrokine-2 (GKN2) and Its Correlation with Tumor-Infiltrating Immune Cells in Lung Cancer and Gastric Cancers.

BACKGROUND: GKN2, as a secretory protein, is involved in the inflammation and immune modulation, and its aberrant expression is closely related to tumorigenesis. However, integrated studies on the value of GKN2 as a promising clinical biomarker and immunotherapy target in multiple tumors are still rare. METHODOLOGY: Multiple online databases, including ONCOMINE, SEGreg, UALCAN, GEPIA, K-M Plotter, cBioPortal, MethSurv, CellMarker, and Timer, were applied to assess the clinical significance of GKN2 and its correlation with tumor-infiltrating immune cells in differentially expressed cancers. RESULTS: Several databases confirmed that GKN2 was significantly down-regulated in lung and gastric cancers compared that in normal samples. GKN2 was altered in 3%, 5%, and 4% of the LUAD, LUSC, and STAD samples, respectively. Hyper-methylation of GKN2 was found in LUAD and LUSC samples. For the clinical values of GKN2, we found that the low transcription level of GKN2 was associated with worse OS in lung cancer, and inferior FP and PPS in gastric cancer, and the relationships between GKN2 expression and clinical variables regarding OS/FP/PPS in lung and gastric cancers were assessed. Moreover, the prognostic value of the DNA methylation patterns of GKN2 in LUAD, LUSC, and STAD was identified. Furthermore, GKN2 expression was found to be significantly correlated with the infiltrating multiple tumor immune cells, and statistically significant differences in the correlation between GKN2 expression and multiple markers of neutrophils and macrophage polarization were observed in LUAD, LUSC, and STAD. CONCLUSION: The study revealed the prognosis and risk factors for deterioration in patients with low expression of GKN2. GKN2 may be used as a valuable prognostic biomarker and therapeutic target in lung and gastric cancers.

Evidence of the Prognostic Value of Pretreatment Systemic Inflammation Response Index in Cancer Patients: A Pooled Analysis of 19 Cohort Studies.

OBJECTIVE: Systemic inflammation response index (SIRI) is a new inflammation-based evaluation system that has been reported for predicting survival in multiple tumors, but the prognostic significance of SIRI in cancers has not been evinced. METHODS: Eligible studies updated on December 31, 2019, were selected according to inclusion criteria, the literature searching was performed in PubMed, Web of Science, Google Scholar, and Cochrane. Hazard ratios (HRs), and 95% confidence intervals (CIs) were extracted and pooled by using Stata/SE 14.1. RESULTS: 11 publications involving 19 cohort studies with a total of 5,605 subjects were included. Meta-analysis results evinced that high SIRI was associated with worse OS (HR = 2.30, 95% CI: 1.87-2.83, p ≤ 0.001), poor CSS/DSS (HR = 2.83, 95% CI: 1.98-4.04, p ≤ 0.001), and inferior MFS/DFS/PFS/RFS/TTP (HR = 1.88, 95% CI: 1.65-2.15, p ≤ 0.001). The association of SIRI with OS was not significantly affected when stratified by diverse confounding factors. It was suggested that tumor patients with high pretreatment SIRI levels would suffer from adverse outcomes. CONCLUSION: High SIRI is associated with unfavorable clinical outcomes in human malignancies; pretreatment SIRI level might be a useful and promising predictive indicator of prognosis in cancers.

Prognostic significance of peripheral blood-derived neutrophil/lymphocyte ratio in patients with digestive cancer.

Accumulating studies reported the clinical value of derived neutrophil/lymphocyte ratio (dNLR) regarding the prediction of survival outcomes in digestive cancers, however, the prognostic significances of dNLR in these cancers were inconsistent. This study was carried out to clarify the relationship between circulating dNLR and prognosis in gastrointestinal (GI) cancers. Eligible publications were collected and extracted by searching Pubmed, Embase, Web of Science, and Google Scholar up to November 21, 2018. The prognostic impact of dNLR in subjects with GI cancers was assessed with the overall hazard ratios (HRs). A total of 26 studies with up to 13,945 participants were recruited. Our findings showed that peripheral blood dNLR before treatment could be a useful prognostic predictor in digestive cancers, an elevated dNLR indicated a shorter overall survival (OS) in GI tumors (HR, 1.44; 95% confidence interval [CI], 1.36-1.51). Furthermore, its significant prognostic value for OS was also confirmed in subgroup analyses stratified by disease type, publication year, type of research, detection method, geographic location, cut-off value, treatment, analysis type, follow-up time and disease stage. In addition, high dNLR was significantly associated with worse cancer-specific survival (HR, 1.25; 95% CI, 1.04-1.47) and inferior event-free survival (HR, 1.22; 95% CI, 1.11-1.33) in patients with digestive cancers. Our study showed elevated peripheral blood dNLR may indicate unfavorable outcomes in digestive cancer.

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.

Calpain Small Subunit 1 Protein in the Prognosis of Cancer Survivors and Its Clinicopathological Correlation.

Background/Aims. Calpain small subunit 1 (Capn4) is implicated in tumorigenesis and plays a key role in multiple tumors. This study aimed to fully illustrate the prognostic value of Capn4 protein in cancer patients. METHODS: A systematic search was conducted against several online databases. Hazard ratios (HRs) or odds ratio (ORs) were used to investigate the relationship between Capn4 protein expression and prognosis as well as clinical parameters in cancer survivors. RESULTS: Eleven studies involving 1775 patients were identified. Overall, the results showed that Capn4 protein was associated with poor prognosis of overall survival (OS) (HR=1.74; 95% CI:1.47-2.01; p<0.001) and event-free survival (EFS) (HR=1.73; 95% CI:1.39-2.07; p<0.001) and event-free survival (EFS) (HR=1.73; 95% CI:1.39-2.07; p<0.001) and event-free survival (EFS) (HR=1.73; 95% CI:1.39-2.07; p<0.001) and event-free survival (EFS) (HR=1.73; 95% CI:1.39-2.07; p<0.001) and event-free survival (EFS) (HR=1.73; 95% CI:1.39-2.07; p<0.001) and event-free survival (EFS) (HR=1.73; 95% CI:1.39-2.07; p<0.001) and event-free survival (EFS) (HR=1.73; 95% CI:1.39-2.07; p<0.001) and event-free survival (EFS) (HR=1.73; 95% CI:1.39-2.07; p<0.001) and event-free survival (EFS) (HR=1.73; 95% CI:1.39-2.07. CONCLUSIONS: Expression of Capn4 protein is associated with cancer survival and clinicopathologic characteristics in patients.

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.

Long non-coding RNA ZFAS1 correlates with clinical progression and prognosis in cancer patients.

Dysregulation of long non-coding RNA zinc finger antisense 1 (ZFAS1) has been reported in many types of cancers. We performed a synthetic analysis to clarify its prognostic significance as a cancer molecular-marker. Several databases (including PubMed, Web of Science, Embase together with Wanfang and China National Knowledge Internet database) were retrieved to identify ZFAS1-related articles. A total of eight articles were included in this meta-analysis. Hazard ratios (HR) and 95% confidence intervals (CI) were applied to assess the association between ZFAS1 expression level and overall survival (OS). Odds ratios (OR) were calculated with RevMan 5.3 software to determine the relationship between ZFAS1 expression and clinicopathologic features. The pooled results of the meta-analysis indicated that high ZFAS1 expression level was positively correlated with poor OS (HR = 1.87, 95% CI: 1.38-2.36, p< 0.001) in human solid cancers. The statistical significance was also observed in subgroup analysis stratified by the cancer type, analysis method, sample size and follow-up time. Furthermore, the elevated ZFAS1 expression was significantly related to positive lymph node metastasis (OR = 4.18, 95% CI: 2.70-6.48, p< 0.001). The present results suggest that ZFAS1 might be served as a novel promising biomarker for prognosis in Chinese patients with solid cancers.

Transducin (ß)-like 1 X-linked receptor 1 correlates with clinical prognosis and clinicopathological characteristics in human solid carcinomas.

Transducin (ß)-like 1 X-linked receptor 1(TBL1XR1) has been reported to be overexpressed in various human cancers, as well as contributing to carcinogenesis and progression. This synthetic analysis was performed to assess whether TBL1XR1 protein could act as a potential prognostic molecular marker for human cancers. Several online databases (PubMed, Web of Science, Embase together with Wanfang and China National Knowledge Internet database) were retrieved to identify TBL1XR1-related publications. A total of ten studies with 1837 cancer patients were included in this meta-analysis. Hazard ratios (HR) with 95% confidence intervals (CI) were applied to assess the association between TBL1XR1 expression and cancer prognosis. Odds ratios (OR) were calculated to determine the relationship between TBL1XR1 expression and clinicopathological characteristics. The overall results revealed that the overexpression of TBL1XR1 was correlated with poorer overall survival (OS) (HR: 1.77, 95% CI: 1.49-2.06, p < 0.001) and worse disease-free survival (DFS) (HR: 1.51, 95% CI: 1.19-1.84, p < 0.001) in human solid cancers. Statistical significance for OS was also found in subgroup analysis stratified by the cancer type, analysis method and follow-up time. Furthermore, elevated TBL1XR1 was associated with unfavorable clinicopathological characteristics including tumor size, depth of invasion, lymph node metastasis and TNM stage. Our meta-analysis suggested that TBL1XR1 might be served as a novel and promising biomarker to predict prognosis and clinicopathologic characteristic for cancer patients.

Overexpression of LncRNA PVT1 Predicts Advanced Clinicopathological Features and Serves as an Unfavorable Risk Factor for Survival of Patients with Gastrointestinal Cancers.

BACKGROUND/AIMS: Many studies have reported that PVT1 played important roles in diverse cancer types. But the systematic analysis of PVT1 in gastrointestinal cancers has not been inspected. Thus, we aimed to investigate clinical value of the long noncoding RNA PVT1 (lncRNA) expression in digestive system cancers. METHODS: Eligible studies were collected from a number of databases (PubMed, Web of Science, Embase, Chinese National Knowledge Infrastructure and Wanfang database). Pooled hazard ratio (HR) or odds ratio (OR) with 95 % confidence interval (95 % Cl) were applied to assess the clinical significance of PVT1. RESULTS: Data from 15 articles were included with a total of 2585 patients. Elevated PVT1 expression were significantly related to poor overall survival (OS) [HR = 1.86, 95% CI (1.44, 2.28); p<0. 0001] in digestive system cancers. The same association was also observed between PVT1 expression with outcomes, including disease free survival (DFS), disease specific survival (DSS) and relapse free survival (RFS). The lncRNA PVT1 could also be predicative for some clinicopathological features. CONCLUSIONS: This meta-analysis revealed that PVT1 may serve as a prognostic predictor and pathological biomarker in digestive system cancers.

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.

Long non-coding RNAs in the development, diagnosis and prognosis of nasopharyngeal carcinoma.

Long noncoding RNAs (lncRNAs), which transcripts longer than 200 nucleotides, are lack of protein coding potential. Emerging studies have shown that lncRNAs play critical roles in carcinogenesis and progression, including human nasopharyngeal carcinoma (NPC). In this article, we first provide an overview on the molecular mechanisms of lncRNAs in NPC, and then discuss the influence of lncRNAs on the diagnosis and treatment of patients with nasopharyngeal carcinoma.

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.