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Poor prognosis of hexokinase 2 overexpression in solid tumors of digestive system: a meta-analysis.

ABSTRACT: Several previous studies have reported the prognostic value of hexokinase 2 (HK2) in digestive system tumors. However, these studies were limited by the small sample sizes and the results were inconsistent among them. Therefore, we conducted a meta-analysis based on 15 studies with 1932 patients to assess the relationship between HK2 overexpression and overall survival (OS) of digestive system malignancies. The relationship of HK2 and clinicopathological features was also evaluated. Hazard ratio (HR) or odds ratio (OR) with its 95% confidence intervals (CI) were calculated to estimate the effect size. Positive HK2 expression showed poor OS in all tumor types (HR = 1.75 [1.41-2.18], P < 0.001). When stratified by tumor type, the impact of HK2 overexpression on poor prognosis was observed in gastric cancer (HR = 1.77 [1.25-2.50], P < 0.001), hepatocellular carcinoma (HR = 1.87 [1.58-2.21], P < 0.001), and colorectal cancer (HR = 2.89 [1.62-5.15], P < 0.001), but not in pancreatic ductal adencarcinoma (HR = 1.11 [0.58-2.11], P = 0.763). Furthermore, high HK2 expression was significantly associated with some phenotypes of tumor aggressiveness, such as large tumor size (OR = 2.03 [1.10-3.74], P = 0.024), positive lymph node metastasis (OR = 2.05 [1.39-3.02], P < 0.001), advanced clinical stage (OR = 2.17 [1.21-3.89], P = 0.009) and high alpha fetoprotein level (OR = 1.47 [1.09-2.02] P = 0.013). In summary, HK2 might act as a prognostic indicator and a potential therapeutic target of these digestive system cancers.

SUBMITTER: Wu J

PROVIDER: S-EPMC5458288 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

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Poor prognosis of hexokinase 2 overexpression in solid tumors of digestive system: a meta-analysis.

Wu Jiayuan J Hu Liren L Wu Fenping F Zou Lei L He Taiping T

Oncotarget 20170501 19

Several previous studies have reported the prognostic value of hexokinase 2 (HK2) in digestive system tumors. However, these studies were limited by the small sample sizes and the results were inconsistent among them. Therefore, we conducted a meta-analysis based on 15 studies with 1932 patients to assess the relationship between HK2 overexpression and overall survival (OS) of digestive system malignancies. The relationship of HK2 and clinicopathological features was also evaluated. Hazard ratio ...[more]

PMID: 28415659

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Project description:ObjectiveFibroblast activation protein (FAP) plays a vital role in tumor invasion and metastasis. Previous studies have reported its prognostic value in different tumors. However, the results of these reports remain controversial. In this study, a meta-analysis was performed to clarify this issue.MethodsA search of the PubMed, Embase and CNKI databases was conducted to analyze relevant articles. The outcomes included the relations between FAP expression and histological differentiation, tumor invasion, lymph node metastasis, distant metastasis and overall survival (OS). Sensitivity analysis by FAP expression in different cells and tumor types were further subjected to sensitivity analyses as subgroups. Pooled odds ratios (ORs) and hazard ratios (HRs) were evaluated using the random-effects model.ResultsThe global analysis included 15 studies concerning various solid tumors. For global analysis, FAP overexpression in tumor tissue displayed significant associations with poor OS and tumor progression (OS: HR = 2.18, P = 0.004; tumor invasion: OR = 4.48, P = 0.007; and lymph node metastasis: OR = 3.80, P = 0.004). The subgroup analyses yielded two notable results. First, the relation between FAP overexpression and poor OS and tumor lymph node metastasis was closer in the patients with FAP expression in tumor cells. Second, the pooled analyses of colorectal cancers or pancreatic cancers all indicated that FAP overexpression was associated with a detrimental OS (HR: 1.72, P = 0.009; HR: 3.18, P = 0.005, respectively). The magnitude of this effect was not statistically significant compared with that in patients with non-colorectal cancers or non-pancreatic cancers. These analyses did not display a statistically significant correlation between FAP expression and histological differentiation and distant metastasis in all of the groups.ConclusionsFAP expression is associated with worse prognosis in solid tumors, and this association is particularly pronounced if FAP overexpression is found in the tumor cells rather than the stroma.

Project description:BackgroundPlenty of studies have showed matrix metalloproteinase 14 (MMP14) expression might be associated with the prognosis of gastric cancer (GC). However, no definite conclusion has been obtained for the contradictory results.MethodsWe searched PubMed, Web of science, Embase, and Cochrane library for eligible studies. The association between MMP14 expression and prognostic outcomes of GC was evaluated. Hazard ratio (HR) and 95% confidence interval (CI) were integrated to show the effect of MMP14 expression on the overall survival (OS) or recurrence-free survival (RFS). Data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) was used to validate the association of MMP14 expression with OS or RFS in GC. A brief bioinformatics analysis was also performed to determine the prognostic role of MMP14 expression in GC.ResultsHigh MMP14 expression was associated with shorter OS compared to low MMP14 expression in GC (HR = 1.95, P < .01). Patients with high MMP14 expression tended to have worse differentiation (P = .03), deeper tumor invasion (P < .01), earlier lymph node metastasis (P < .01), earlier distant metastasis (P < .01) and more advanced clinical stage (P < .01) compared to those with low MMP14 expression. The data from TCGA and GEO showed MMP14 was overexpressed in tumor tissues compared to normal tissues (P < .05), and high MMP14 expression was significantly related to shorter OS (HR = 1.70, 95% CI = 1.32-2.20, P < .01) and RFS (HR = 1.45, 95% CI = 1.15-1.83, P < .01) compared to low MMP14 expression in GC. Expression of MMP14 was linked to functional networks involving the biological process, metabolic process, response to stimulus, cell communication and so on. Functional network analysis suggested that MMP14 regulated the protein digestion and absorption, extracellular matrix receptor interaction, focal adhesion, ribosome, spliceosome, and so on.ConclusionHigh MMP14 expression was associated with worse prognosis of GC compared to low MMP14 expression. MMP14 expression could serve as a prognostic factor and potential therapeutic target of GC.

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Poor prognosis of hexokinase 2 overexpression in solid tumors of digestive system: a meta-analysis.

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Poor prognosis of hexokinase 2 overexpression in solid tumors of digestive system: a meta-analysis.

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