Dataset Information

High delta-like ligand 4 expression correlates with a poor clinical outcome in gastric cancer.

ABSTRACT: Background: Emerging evidence suggests that delta-like ligand 4 (DLL4) and other members of the Notch pathway may offer new targets for development of anti-angiogenesis drugs for the treatment of several tumor types. However, the role of DLL4 in gastric cancer (GC) remains unclear. In this study, we investigated the impact of DLL4 overexpression on recurrence and survival in gastric cancer (GC) patients. Methods: DLL4 expression levels were evaluated by immunohistochemistry in tissue samples from 336 GC patients. Samples were classified into high and low DLL4 expression according to a cut-off of 50% positively stained cells. The correlation between DLL4 expression and clinicopathological parameters, disease-free survival (DFS), and overall survival (OS) were statistically analyzed. Results: High DLL4 expression was observed in 67 (19.9%) of the 336 GC patients. After a median follow-up duration of 54.97 months [95% confidence interval (CI), 52.40-57.55 months), patients at stage II-IV with high DLL4 expression showed significantly poorer DFS compared with those at the same stage but with low DLL4 expression [not reached (NR) for both cohorts, hazard ratio (HR) 0.73 (95% CI, 0.38-1.40); p = 0.007]. Likewise, GC patients with high DLL4 expression had a significantly shorter OS following curative surgery compared to those with low DLL4 expression [NR for both groups, HR 0.56 (95% CI, 0.32-0.96; p = 0.002]. High DLL4 expression had a greater influence on DFS in stage IIIb/IV patients than in patients at early stages [34.87 vs. 10.1 months; HR, 0.44 (95% CI, 0.19-0.96); p = 0.004]. Moreover, stage IIIb/IV patients with high DLL4 expression had a significantly shorter OS after surgery than those with low DLL4 expression [58.87 vs. 16.93 months, HR 0.39 (95% CI, 0.16-0.99), p = 0.001). Conclusion: High DLL4 expression was observed in 19.9% of GC patients and was significantly associated with poor survival following curative surgery. Given its prevalence in the GC cohort with a poor prognosis, DLL4 is a potential therapeutic target.

SUBMITTER: Kim Y

PROVIDER: S-EPMC6603391 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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High delta-like ligand 4 expression correlates with a poor clinical outcome in gastric cancer.

Kim Youjin Y Byeon Sun-Ju SJ Hur Joonyoung J Lee Kangkook K Kim Dongin D Ahn Jin-Hyung JH Lee Sang Hoon SH You Weon-Kyoo WK Kim Seung Tae ST Park Se Hoon SH Kang Won Ki WK Kim Kyoung-Mee KM Lee Jeeyun J

Journal of Cancer 20190602 14

<b>Background</b>: Emerging evidence suggests that delta-like ligand 4 (DLL4) and other members of the Notch pathway may offer new targets for development of anti-angiogenesis drugs for the treatment of several tumor types. However, the role of DLL4 in gastric cancer (GC) remains unclear. In this study, we investigated the impact of DLL4 overexpression on recurrence and survival in gastric cancer (GC) patients. <b>Methods</b>: DLL4 expression levels were evaluated by immunohistochemistry in tiss ...[more]

PMID: 31289587

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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.

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High delta-like ligand 4 expression correlates with a poor clinical outcome in gastric cancer.

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High delta-like ligand 4 expression correlates with a poor clinical outcome in gastric cancer.

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