Dataset Information

Elevated FOXO6 expression correlates with progression and prognosis in gastric cancer.

ABSTRACT: The FOXO6 correlated with tumor progression in a wide range of carcinomas, yet little is known in gastric cancer. The expression of FOXO6 and matrix metallopeptidase 9 (MMP-9) was assessed by immunohistochemistry in 192 gastric carcinoma specimens. The correlation between FOXO6 expression with MMP-9, clinicopathological/prognostic value in gastric cancer was examined. FOXO6 overexpression was significantly associated with depth of invasion, lymph node metastasis and stage of disease. In univariate and multivariate analyses, FOXO6 was an independent prognostic factor for both overall survival (OS) and recurrence-free survival (RFS). Moreover, FOXO6 over-expression was correlated with poor prognosis in patients subgroups stratified by tumor size, depth of invasion and lymph node metastasis. FOXO6 expression was increased in both prominent serosal invasion group and lymph node metastasis group. In addition, FOXO6 expression was positively correlated with MMP-9 among 192 gastric cancer tissues. Patients with FOXO6 over-expression had poor OS and shorter RFS in low and high invasiveness groups. Furthermore, stratified analysis showed that the TNM stage I patients with high FOXO6 expression had poor prognosis than those with low FOXO6 expression. In conclusion, FOXO6 overexpression promotes tumor aggressiveness and prognosis, and could be a promising target for prognostic prediction in gastric cancer patients.

Condensed abstract

The aim of this study was to analyze the role of FOXO6 in patients with gastric carcinoma. FOXO6 may play an important role on tumor invasion, metastasis and prognosis. It may also serve as a novel target for prognostic prediction.

SUBMITTER: Wang JH

PROVIDER: S-EPMC5458239 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

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Elevated FOXO6 expression correlates with progression and prognosis in gastric cancer.

Wang Jia-Hong JH Tang Hong-Sheng HS Li Xiao-Shan XS Zhang Xiang-Liang XL Yang Xian-Zi XZ Zeng Li-Si LS Ruan Qiang Q Huang Yong-Hong YH Liu Gao-Jie GJ Wang Jin J Cui Shu-Zhong SZ

Oncotarget 20170501 19

The FOXO6 correlated with tumor progression in a wide range of carcinomas, yet little is known in gastric cancer. The expression of FOXO6 and matrix metallopeptidase 9 (MMP-9) was assessed by immunohistochemistry in 192 gastric carcinoma specimens. The correlation between FOXO6 expression with MMP-9, clinicopathological/prognostic value in gastric cancer was examined. FOXO6 overexpression was significantly associated with depth of invasion, lymph node metastasis and stage of disease. In univaria ...[more]

PMID: 28404958

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Project description:BackgroundGastric cancer (GC) is one of the most common and fatal cancers worldwide. Effective biomarkers to aid the early diagnosis of GC, as well as predict the course of disease, are urgently needed. Hence, we explored the role and function of cadherin-6 (CDH6) in the diagnosis and prognosis of gastric cancer.MethodsThe expression levels of CDH6 in cancerous and normal gastric tissue were analyzed using multiple public databases. Gene set enrichment analysis (GSEA) was performed using The Cancer Genome Atlas (TCGA) dataset. The diagnostic efficiency of CDH6 expression in GC patients was determined through receiver operating characteristic (ROC) curve analysis. The associations between clinical variables and CDH6 expression were evaluated statistically, and the prognostic factors for overall survival were analyzed by univariate and multivariate Cox regression. 44 GC tissue samples, 20 donor-matched adjacent normal tissue samples, and associated detailed clinical information, were collected from the Tianjin Medical University General Hospital. CDH6 expression levels were determined for further validation.ResultsCDH6 was upregulated in GC samples compared to normal gastric tissue. Furthermore, GSEA identified the tricarboxylic acid (TCA) cycle, extracellular matrix (ECM) receptor interaction, glyoxylate and dicarboxylate metabolism, oxidative phosphorylation, and the pentose phosphate pathway as differentially enriched in GC tissue samples. According to the area under the ROC curve (AUC) values (AUC = 0.829 in the TCGA and 0.966 in the GSE54129 dataset), CDH6 expression was associated with high diagnostic efficacy. Patients with high CDH6 levels in their GC tissues had a higher T number (according to the TNM classification) and a worse prognosis than those with low CDH6 expression. Univariate and multivariate Cox regression analysis showed that CDH6 was an independent risk factor for overall survival (univariate: HR = 1.305, P = 0.002, multivariate: HR = 1.481, P < 0.001).ConclusionCDH6 was upregulated in GC, and high CDH6 expression was indicative of a higher T number and a worse prognosis. Therefore, CDH6 represents a potentially independent molecular biomarker for the diagnostic and prognostic prediction of GC.

Project description:P53-induced gene 11 (PIG11) is an early transcription-related target of p53 that is involved in cell apoptosis and tumor development. However, its biological function in gastric cancer (GC) tissues and relationship with the prognosis of patients with GC have remained elusive. In the present retrospective study, 60 fresh and 790 paraffin-embedded samples of GC were obtained from the Affiliated Hospital of Nantong University (Nantong, China) with complete clinical data from all patients. Reverse transcription-quantitative PCR and tissue microarray-immunohistochemical analysis were used to determine the expression of PIG11 in the respective GC tissues. A receiver operating characteristic (ROC) curve was plotted to determine the diagnostic utility of PIG11 expression in GC. Furthermore, three online databases, including Gene Expression Profiling Interactive Analysis (GEPIA), Oncomine and Kaplan-Meier plotter, were used for bioinformatics analysis of PIG11. PIG11 expression in GC tissues was high, which was positively correlated with invasive depth (P<0.001), lymph node metastasis (P<0.001), distant metastasis (P=0.019), TNM staging (P<0.001) and carcinoembryonic antigen in serum (P<0.001), and negatively associated with the overall survival of patients with GC. The ROC curve analysis suggested that based on PIG11 expression, it was possible to distinguish GC tissues from adjacent normal tissues (P<0.0001) with a sensitivity and specificity of 81.67 and 76.67%, respectively. In addition, Cox logistic regression analysis demonstrated that high PIG11 expression is a novel biomarker for unfavorable prognosis of patients with GC. Furthermore, the results obtained from the GEPIA database indicated that PIG11 expression is correlated with TNF, carcinoembryonic antigen related cell adhesion molecule 5, phosphatidylinositol-4, 5-bisphosphate 3-kinase catalytic subunit alpha, VEGFA and kinase insert domain receptor. Therefore, PIG11 expression may be associated with the malignancy of GC and may serve as a potential diagnostic and prognostic biomarker for GC.

Project description:Background: Insulin-like growth factor binding protein-7 (IGFBP7) contributes to multiple biological processes in various tumors. However, the role of IGFBP7 in gastric cancer (GC) is still undetermined. The study aims to explore the role of IGFBP7 in GC via an integrated bioinformatics analysis. Methods: IGFBP7 expression levels in GC and its normal gastric tissues were analyzed using multiple databases, including the Tumor Immune Estimation Resource (TIMER), Oncomine, The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, as well as by our clinical gastric specimens. The methylation analysis was conducted with MEXPRESS, UALCAN and Xena online tools. The survival analysis was conducted using the Kaplan-Meier Plotter and Gene Expression Profiling Interactive Analysis (GEPIA) databases. Coexpressed genes of IGFBP7 were selected with the cBioPortal tool and enrichment analysis was conducted with the clusterProfiler package in R software. Gene set enrichment analysis (GSEA) was performed to explore the IGFBP7-related biological processes involved in GC. Correlations between IGFBP7 and immune cell infiltrates were analyzed using the TIMER database. Results: IGFBP7 expression was significantly upregulated in GC and correlated with stage, grade, tumor status and Helicobacter pylori infection. High IGFBP7 expression and low IGFBP7 methylation levels were significantly associated with short survival of patients with GC. Univariate and multivariate analyses revealed that IGFBP7 was an independent risk factor for GC. The coexpressed genes LHFPL6, SEPTIN4, HSPB2, LAYN and GGT5 predicted unfavorable outcomes of GC. Enrichment analysis showed that the coexpressed genes were involved in extracellular matrix (ECM)-related processes. GSEA indicated that IGFBP7 was positively related to ECM and inflammation-related pathways. TIMER analysis indicated that the mRNA level of IGFBP7 was strongly correlated with genes related to various infiltrating immune cells in GC, especially with gene markers of tumor associated macrophages (TAMs). Conclusions: Increased IGFBP7 expression correlates with poor prognosis and immune cell infiltration in GC, which might be a potential biomarker for the diagnosis of GC.

Dataset Information

Elevated FOXO6 expression correlates with progression and prognosis in gastric cancer.

Condensed abstract

Publications

Elevated FOXO6 expression correlates with progression and prognosis in gastric cancer.

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