Overexpression of FNDC1 in Gastric Cancer and its Prognostic Significance.
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ABSTRACT:
SUBMITTER: Ren J
PROVIDER: S-EPMC6299387 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundHigh mobility group protein A2 (HMGA2) overexpression has been reported to be closely related to tumor progression [1-4] and indicate significantly worse overall survival in gastric cancer [5-8]. However, a final consensus regarding this issue has not yet been reached. Thus, we conducted a meta-analysis to evaluate the association between HMGA2 expression and prognosis of gastric cancer patients.MethodsThe Cochrane Library, Embase, PubMed, Web of Science and China Biology Medicine databases were searched to identify eligible literature published prior to September 2016. In the included studies, the level of HMGA2 amplification was evaluated by immunohistochemistry. We performed a meta-analysis, and pooled relative risk (RRs), hazard ratio (HRs), and 95% confidence intervals (CIs) were analyzed using Review Manager 5.3.ResultsSix studies [5-7, 9-11] involving 712 gastric cancer patients were included and stratified by HMGA2 amplification magnitude. The results of the analysis indicated that higher HMGA2 levels were associated with several clinicopathological parameters and predicted poor prognosis in terms of overall survival (OS).ConclusionsThe results of the present study indicate that higher HMGA2 levels were significantly associated with TNM stage, lymph node status, vascular invasion, and poor OS in patients with gastric cancer. In conclusion, HMGA2 may serve as a promising prognostic biomarker in gastric cancer.
| S-EPMC5725036 | biostudies-literature
Project description:ObjectiveThe prognostic significance of CD24 expression for survival in patients with gastric cancer remains controversial. We conducted a meta-analysis to investigate the impact of CD24 expression on clinicopathological features and survival outcomes in gastric cancer.MethodsA comprehensive literature search of the electronic databases PubMed, Embase, Web of Science and China National Knowledge Infrastructure (CNKI; up to April 8, 2014) was performed for relevant studies using multiple search strategies. Correlations between CD24 expression and clinicopathological features and overall survival (OS) were analyzed.ResultsA total of 1,041 patients with gastric cancer from 9 studies were included. The pooled odds ratios (ORs) indicated CD24 expression was associated with tumor depth (OR = 0.45, 95% confidence interval [CI] = 0.32-0.63; P<0.00001), status of lymph nodes (OR = 0.40, 95% CI = 0.25-0.64; P = 0.0001) and tumor node metastasis (TNM) stage (OR = 0.56, 95% CI = 0.41-0.77; P = 0.0003). The pooled hazard ratio (HR) for OS showed overexpression of CD24 reduced OS in gastric cancer (HR = 1.99, 95% CI = 1.29-3.07, P = 0.002). Whereas, combined ORs showed that CD24 expression had no correlation with tumor differentiation or Lauren classifications.ConclusionCD24 overexpression in patients with gastric cancer indicated worse survival outcomes and was associated with common clinicopathological poor prognostic factors.
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Project description:BACKGROUND The aim of this study was to investigate the expression level of martrilin-3 (MATN3) in patients with gastric adenocarcinoma (GAC) and to investigate the prognostic significance of MATN3. MATERIAL AND METHODS Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) data were used to predict the expression and prognostic value of MATN3 mRNA in GAC patients. Seventy-six GAC patients had GAC tissue samples and paired adjacent normal tissue samples collected retrospectively to examine the MATN3 protein expression level by immunohistochemical staining. Furthermore, Kaplan-Meier univariate and Cox multivariate analyses were used to verify the correlation between MATN3 expression and clinicopathological parameters of GAC patients and the prognostic significance of MATN3. RESULTS The GEO and TCGA data predicted that MATN3 mRNA levels were significantly higher in GAC tissue compared to normal tissue (all p<0.05). Further survival analyses showed that GAC patients with high mRNA expression of MATN3 had significantly lower disease-free survival (DFS) and overall survival (OS) time than those with low mRNA expression of MATN3 (all p<0.05). Subsequent immunohistochemical staining results confirmed that the MATN3 protein levels in GAC tissues were highly expressed (p=0.000) compared to normal tissues. In addition, GAC patients with high protein expression of MATN3 had remarkably decreased OS compared to patients with low protein expression of MATN3 (p=0.000). Univariate and multivariate survival analyses revealed that MATN3 high expression could be used as an independent predictor of poor prognosis in GAC patients (all p=0.000). CONCLUSIONS This study confirmed that MATN3 protein was highly expressed in GAC patients, and MATN3 overexpression could be used as an independent predictor of poor prognosis in GAC patients.
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Project description:BACKGROUND The aim of this study was to examine the expression level of IRRE-like protein 1 (KIRREL) in gastric cancer (GC) and to explore its prognostic significance. MATERIAL AND METHODS Bioinformatics methods were used to predict the differential expression levels of KIRREL mRNA in GC and normal gastric tissues by mining cancer-related databases (TCGA and Oncomine). Immunohistochemistry was done to verify the KIRREL protein expression levels in 71 cases of GC tissues combined with matched normal tissues. The relationship between clinicopathologic parameters and KIRREL differential expression levels in GC was investigated by the chi-square test. Kaplan-Meier univariate and Cox multivariate survival analyses were performed to explore the prognostic significance of KIRREL expression in GC patients. RESULTS TCGA and GEO data analyses showed that KIRREL mRNA expression level was remarkably higher in GC than that in normal gastric tissues (both P<0.05). KIRREL mRNA levels were dramatically increased from stage I to stage IV (P=0.037). Immunohistochemical results showed that the high positive rate of KIRREL staining in GC was 61.97% (44/71). Moreover, GC patients with KIRREL mRNA or protein high levels had significantly shorter overall survival times than those with KIRREL mRNA or low protein levels (All P<0.05). Additionally, Cox multivariate survival analysis revealed that KIRREL differential expression levels (low vs. high) were the only independent parameter predicting the prognosis of GC patients (P=0.000). CONCLUSIONS KIRREL was overexpressed in GC and the overexpression of KIRREL could serve as an independent predictor of poor prognosis in GC patients.
| S-EPMC5952805 | biostudies-literature
Project description:Meiotic recombination 11 (MRE11) plays a critical role in the DNA damage response and maintenance of genome stability and is associated with the prognosis for numerous malignancies. Here, we explored the clinicopathological significance and prognostic value of MRE11 expression in colorectal cancer (CRC), a leading cause of cancer-related deaths worldwide. Samples from 408 patients who underwent surgery for colon and rectal cancer between 2006 and 2011, including a sub-cohort of 127 (31%) patients treated with adjuvant therapy, were analyzed. In Kaplan-Meier survival analyses, we found that high MRE11 expression in the tumor center (TC) was significantly associated with poor disease-free survival (DFS; p = 0.045) and overall survival (OS; p = 0.039). Intriguingly, high MRE11 expression in the TC was also significantly correlated with reduced DFS (p = 0.005) and OS (p = 0.010) in the subgroup with right-sided primary CRC. In multivariate analyses, high MRE11 expression (hazard ratio [HR] = 1.697, 95% confidence interval [CI]: 1.034-2.785; p = 0.036) and lymphovascular/perineural invasion (LVI/PNI; HR = 1.922, 95% CI 1.122-3.293; p = 0.017) showed significant association with worse OS in patients with right-sided tumors but not those with left-sided tumors. Moreover, in patients with right-sided tumors, high MRE11 was associated with worse OS for those with lymph node involvement (p = 0.006) and LVI/PNI (p = 0.049). Collectively, our results suggest that MRE11 may serve as an independent prognostic marker in those with right-sided severe CRC, with clinical value in the management of these patients.
| S-EPMC10177562 | biostudies-literature
Project description:The aim of this study was to assess the relative prognostic value of biomarkers to measure the systemic inflammatory response (SIR) and improve prognostic modeling in a cohort of patients undergoing potentially curative surgery for gastric adenocarcinoma. The hypothesis was that a single SIR biomarker would be associated with the most prognostic value.Consecutive 331 patients undergoing surgery for gastric cancer between 2004 and 2016 within a regional UK cancer network were identified. Serum measurements of hemoglobin, C-reactive protein, albumin, modified Glasgow Prognostic Score, and differential white cell counts were obtained before surgery, and correlated with histopathological factors (pTNM stage, differentiation, and vascular invasion) and survival. Primary outcome measures were disease-free (DFS) and overall survival (OS).Consecutive 331 patients were identified and 291 underwent potentially curative gastrectomy for adenocarcinoma. On univariable DFS analysis, female gender (p = 0.027), proximal location (p = 0.018), pT stage (p < 0.001), pN stage (p < 0.001), pTNM stage (p < 0.001), vascular invasion (p < 0.001), poor differentiation (p = 0.001), lymph node ratio (p < 0.001), R1 status (p < 0.001), platelet count (p = 0.038), and mGPS (p = 0.001) were significantly associated with poor survival. The mGPS was associated with advanced pT stage (p = 0.001), pTNM stage (p = 0.013), and poor differentiation (p = 0.030). On multivariable DFS analysis, mGPS [hazard ratio (HR) 2.51, 95% confidence interval (CI) 1.35-4.65, p = 0.011] was the only inflammatory marker to retain independent significance. Multivariable OS analysis revealed similar findings; mGPS (HR 2.75, (95% CI 1.65-4.59), p < 0.001).mGPS is an important and only SIR-related prognostic biomarker independently associated with both DFS and OS in gastric cancer.
| S-EPMC5869874 | biostudies-other
Project description:Gastric cancer is a common human cancer worldwide. Fibronectin is an important extracellular matrix protein that has been implicated in many cancers and is known to be associated with proliferation and migration. Fibronectin type III domain containing 1 (FNDC1) contains a major component of the structural domain of fibronectin. The objectives of the present study were to measure FNDC1 expression in gastric cancer tissues and evaluate its value as a potential prognostic marker for gastric cancer. FNDC1 protein expression was analyzed by immunohistochemistry in 98 samples of gastric cancer tissue and 25 adjacent normal tissues. The associations between FNDC1 level and various clinicopathological characteristics were assessed, and the correlation between FNDC1 expression levels and prognosis of patients with gastric cancer was analyzed using a Kaplan-Meier analysis. It was demonstrated that FNDC1 expression in gastric cancer tissues and adjacent tissues was significantly different. FNDC1 expression levels were significantly higher in gastric cancer tissues compared with normal gastric tissues (P<0.001). Among the clinicopathological characteristics evaluated, clinical stage (P<0.001), T classification (P<0.001), N classification (P<0.001) and pathological differentiation (P=0.044) were significantly associated with high FNDC1 expression. Higher FNDC1 expression level was significantly correlated with poorer survival. The present findings suggest that FNDC1 expression levels may be a promising prognostic biomarker for gastric cancer.
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Project description:Background: Lumican (LUM) is a member of the small leucine-rich proteoglycan family and plays dual roles as an oncogene and a tumor suppressor gene. The effect of LUM on tumors is still controversial. Methods: Gene expression profiles and clinical data of gastric cancer (GC) were downloaded from The Cancer Genome Atlas (TCGA) database. The expression difference of LUM in GC tissues and adjacent nontumor tissues was analyzed by R software and verified by quantitative real-time polymerase chain reaction (qRT-PCR) and comprehensive meta-analysis. The relationship between LUM expression and clinicopathological parameters was assessed by chi-square test and logistic regression. Kaplan-Meier survival analysis and Cox proportional hazards regression model were chosen to assess the effect of LUM expression on survival. Gene set enrichment analysis (GSEA) was used to screen the signaling pathways involved in GC between the low and the high LUM expression datasets. Results: The expression of LUM in GC tissues was significantly higher than that in adjacent nontumor tissues (P < 0.001) from the TCGA database. qRT-PCR (P = 0.022) and comprehensive meta-analysis (standard mean difference = 0.90, 95% CI: 0.34-1.46) demonstrated that LUM was upregulated in GC. The chi-square test showed that the high expression of LUM was correlated with tumor differentiation (P = 0.024) and T stage (P = 0.004). Logistic regression analysis showed that high LUM expression was significantly correlated with tumor differentiation (OR = 1.543 for poor vs. well or moderate, P = 0.043), pathological stage (OR = 3.149 for stage II vs. stage I, P = 0.001; OR = 2.505 for stage III vs. stage I, P = 0.007), and T classification (OR = 13.304 for T2 vs. T1, P = 0.014; OR = 18.434 for T3 vs. T1, P = 0.005; OR = 30.649 for T4 vs. T1, P = 0.001). The Kaplan-Meier curves suggested that patients with high LUM expression had a poor prognosis. Multivariate analysis showed that a high expression of LUM was an important independent predictor of poor overall survival (HR, 1.189; 95% CI, 1.011-1.400; P = 0.037). GSEA indicated that 14 signaling pathways were evidently enriched in samples with the high-LUM expression phenotype. Conclusions: LUM might act as an oncogene in the progression of GC and could be regarded as a potential prognostic indicator and therapeutic target for GC.
| S-EPMC7242722 | biostudies-literature
Project description:Background: PSMD1 has been considered to be involved in many human cancers, but its prognostic significance in gastric cancer (GC) has not been elucidated. The aim of this study was to evaluate the prognostic value of PSMD1 expression in tumor tissues of GC patients. Methods: We retrospectively analyzed the expression of PSMD1 in 241 paraffin-embedded GC specimens of the training cohort by immunohistochemistry. The prognostic value of PSMD1 expression was assessed using Kaplan-Meier survival curves and multivariate COX regression models. PSMD1 expression and other GC-associated risk factors were used to generate two nomograms to evaluate prognosis, and the performance of the two nomograms was assessed with respect to its calibration, discrimination, and clinical usefulness. Further validation was performed using an independent cohort of 170 cases. Results: High PSMD1 expression was significantly associated with decreased disease-free survival (DFS) and overall survival (OS) in GC patients. Furthermore, multivariate Cox proportional hazard analysis demonstrated that PSMD1 was an independent prognostic factor for DFS and OS. The two nomograms that were developed by integrating PSMD1 expression and the TNM staging system showed better prediction of DFS and OS than TNM staging system alone(C-index for training cohort: 0.708 (95% CI:0.670-0.746) and 0.712 (0.671-0.752), respectively; C-index for validation cohort: 0.704 (0.651-0.757) and 0.711 (0.656-0.767), respectively). Decision curve analysis demonstrated that the nomograms showed potential for clinical use. Conclusion: Intratumoral PSMD1 expression is a novel independent predictor of DFS and OS in GC patients. In the future, large-scale prospective studies will be necessary to confirm our findings regarding its potential prognostic and therapeutic value for GC patients.
| S-EPMC6691719 | biostudies-literature
Project description:Gastric cancer (GC) is one of the most typical cancerous neoplasms occurring in the digestive system. For advanced GC, immunotherapy is the final option for them to prolong survival time. Hence, we aimed to identify new molecular targets to enhance the immunotherapy response in GC individuals. Then we applied bioinformatic analysis to explore the expression profiles of G-protein-coupled receptor 27 (GPR27) transcription and GPR27 methylation. The associations between survival of GC patients and GPR27 transcription and methylation were then analyzed. We also studied the link between GPR27 expression and levels of immune cell infiltration. Finally, we gained insights into the prognostic role of GPR27 protein in 97 cases of GC individuals. According to datasets gained from TCGA, GPR27 mRNA is expressed lower in GC tissues. Down-regulation of GPR27 transcription was related with better survival in GC individuals, and GPR27 cg03024619 had the most significant prognostic value (HR=0.553, P<0.0001). In addition, the expression level of GPR27 has a clear interaction with immune cells' infiltration and their markers. Single-cell analysis displayed that GPR27 is mainly expressed in macrophages. Finally, down-regulation of GPR27 protein was observed in GC tissues and correlated with better survival outcomes. GPR27 can serve as an important prognostic biomarker and exert an immunomodulatory role in GC. Our findings highlight the significance of GPR27 in a variety of cancers, including GC, and provide clues for a better understanding of GPR27 from bioinformatics and clinically validated perspective.
| S-EPMC10522374 | biostudies-literature