Clinical significance of zinc-finger E-box binding homeobox 1 mRNA levels in peritoneal washing for gastric cancer

Yabusaki, Norimitsu; Yamada, Suguru; Murai, Toshifumi; Kanda, Mitsuro; Kobayashi, Daisuke; Tanaka, Chie; Fujii, Tsutomu; Nakayama, Goro; Sugimoto, Hiroyuki; Koike, Masahiko; Nomoto, Shuji; Fujiwara, Michitaka; Kodera, Yasuhiro

doi:10.3892/mco.2014.462

Cited by 11 publications

(9 citation statements)

References 36 publications

(50 reference statements)

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“…ZEB family members, ZEB1 and ZEB2, are transcriptional factors suppressing E-cadherin, and they play a decisive role in tumor metastasis. Substantial evidence showed that intense expression of ZEB1 associates with both primary gastric cancer and peritoneal diffusion which predicted earlier recurrence as well as lower disease-free survival rate (34,35). Murai et al (36) classified 116 GC patients into epithelial or mesenchymal group through Vimentin/E-cadherin ratio (V/E), as they pointed, the mesenchymal group with high V/E ratio indicated an EMT status and carried anomalous ZEB1 expression, suggesting aggressive clinicopathological characteristics and poorer survival.…”

Section: Epithelial-mesenchymal Transition and Gastric Cancermentioning

confidence: 99%

Interaction between Wnt/β-catenin pathway and microRNAs regulates epithelial-mesenchymal transition in gastric cancer (Review)

Zhuang

Jiang

et al. 2016

International Journal of Oncology

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Abstract. Gastric cancer (GC) is the third primary cause of cancer-related mortality and one of the most common type of malignant diseases worldwide. Despite remarkable progress in multimodality therapy, advanced GC with high aggressiveness always ends in treatment failure. Epithelialmesenchymal transition (EMT) has been widely recognized to be a key process associating with GC evolution, during which cancer cells go through phenotypic variations and acquire the capability of migration and invasion. Wnt/β-catenin pathway has established itself as an EMT regulative signaling due to its maintenance of epithelial integrity as well as tight adherens junctions while mutations of its components will lead to GC initiation and diffusion. The E-cadherin/β-catenin complex plays an important role in stabilizing β-catenin at cell membrane while disruption of this compound gives rise to nuclear translocation of β-catenin, which accounts for upregulation of EMT biomarkers and unfavorable prognosis. Additionally, several microRNAs positively or negatively modify EMT by reciprocally acting with certain target genes of Wnt/β-catenin pathway in GC. Thus, this review centers on the strong associations between Wnt/β-catenin pathway and microRNAs during alteration of EMT in GC, which may induce advantageous therapeutic strategies for human gastric cancer.

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Section: Epithelial-mesenchymal Transition and Gastric Cancermentioning

confidence: 99%

Interaction between Wnt/β-catenin pathway and microRNAs regulates epithelial-mesenchymal transition in gastric cancer (Review)

Zhuang

Jiang

et al. 2016

International Journal of Oncology

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“…The systematic literature search yielded 31 studies, including 3224 patients with GC for inclusion in the final analysis ( Fig 1 and Table 1 ). Based on survival analyses, all of the patients in 15 of the included studies showed negative conventional pathological cytology of the PF (cytology - )[ 37 , 38 , 39 , 40 , 26 , 41 , 42 , 10 , 43 , 13 , 44 , 45 , 46 , 47 , 48 ]. In 14 of the studies, curative treatments were applied to all patients who were included in the survival analyses [ 37 , 42 , 49 , 10 , 11 , 50 , 51 , 52 , 26 , 44 , 43 , 45 , 41 , 53 ].…”

Section: Resultsmentioning

confidence: 99%

“…The baseline characteristics of the included studies are summarized in Table 1 . After assessing the risk of bias for the individual studies, 13 studies had a high risk of bias[ 56 , 42 , 46 , 50 , 59 , 44 , 60 , 61 , 48 , 45 , 58 , 53 , 47 ] and 18 studies had a low risk of bias[ 37 , 38 , 51 , 54 , 39 , 40 , 52 , 12 , 49 , 26 , 41 , 25 , 11 , 55 , 10 , 43 , 13 , 57 ] ( S3 Table online). Thirteen of the included studies confirmed that the MAPF status was confirmed as an independent prognostic factor in multivariate Cox regression analysis.…”

Section: Resultsmentioning

confidence: 99%

“…To control for variability generated from PF cytology status, studies evaluating cytology - patients were pooled. Fifteen studies were selected to evaluate the prognostic effects of various endpoints (OS[ 37 , 46 , 10 , 44 , 40 , 41 , 38 ], DFS[ 42 , 26 , 43 , 48 , 47 , 38 ] and PRF[ 46 , 10 , 39 , 45 , 38 , 13 ]) for GC. MAPF + patients had poor prognoses for OS (HR 2.59, 95%CI 1.99–3.37, n = 7, I 2 = 9.2%, P Q = 0.359), DFS (HR 4.92, 95%CI 3.28–7.37, n = 6, I 2 = 7.3%, P Q = 0.370) and PRF (HR 2.81, 95%CI 2.12–3.72, n = 6, I 2 = 35.3%, P Q = 0.172), as shown in Table 2 .…”

Section: Resultsmentioning

confidence: 99%

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Prognostic Significance of Molecular Analysis of Peritoneal Fluid for Patients with Gastric Cancer: A Meta-Analysis

et al. 2016

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BackgroundAccurately distinguishing serosal invasion in patients with gastric cancer (GC) prior to surgery can be difficult. Molecular analysis of peritoneal fluid (MAPF) for free cancer cells with higher sensitivity than other methods; however, its prognostic value for GC remains controversial, precluding its application in clinical practice.MethodsPubMed, EMBASE and other databases were systematically searched. Thirty-one studies were eligible for the meta-analysis. Hazard ratios (HRs) and 95% confidence intervals (CIs) were pooled for overall survival (OS), disease-free survival (DFS) and peritoneal recurrence-free survival (PRF).ResultsThe current meta-analysis focused on patients with GC and negative cytological diagnoses. The results showed that positive MAPF status (MAPF+) led to poorer prognoses for OS (HR 2.59, 95% CI 1.99–3.37), DFS (HR 4.92, 95% CI 3.28–7.37) and PRF (HR 2.81, 95% CI 2.12–3.72) compared with negative MAPF status (MAPF-). Moreover, among the patients with GC who received curative treatment, the MAPF+ patients had poorer prognoses for OS (HR 3.27, 95% CI 2.49–4.29), DFS (HR 3.90, 95% CI 2.74–5.57) and PRF (HR 5.45, 95% CI 3.70–8.03). A meta-analysis of multivariate-adjusted HRs demonstrated that MAPF+ status was an independent prognostic factor for patients with GC who underwent curative treatment (OS: HR 2.19, 95% CI 1.47–3.28; PRF: HR 3.44, 95% CI 2.01–5.87). Using the identical target genes (CEA, CEA/CK20) as molecular markers, the patients with GC who were MAPF+ had significantly worse prognoses for OS (CEA: HR 3.03, 95% CI 2.29–4.01; CEA/CK20: HR 4.24, 95% CI 2.42–7.40), DFS (CEA: HR 3.99, 95% CI 2.24–7.12; CEA/CK20: HR 4.31, 95% CI 1.49–2.48) and PRF (CEA: HR 4.45, 95% CI 2.72–7.31; CEA/CK20: HR 6.46, 95% CI 3.62–11.55) than the patients who were MAPF-.Conclusion/SignificanceThe above results demonstrate that MAPF could be a prognostic indicator for patients with GC who have a negative cytological diagnosis and/or are receiving curative treatment. MAPF could provide clinicians with additional prognostic information that could aid in developing individualized treatment plans prior to surgery. The widely used target genes CEA, CEA/CK20 were confirmed to be valuable MAPF markers for predicting the prognosis of GC.

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“…3A). In fact, ZEB1 upregulation has well-characterized oncogenic effects on gastric cancer (13,23). By using the UCSC Xena browser (Fig.…”

Section: Knockdown Of Lama4 Impaired the Migration And Invasion Of Gamentioning

confidence: 99%

LAMA4 expression is activated by zinc finger E‑box‑binding homeobox�1 and independently predicts poor overall survival in gastric cancer

Wang

Hou²,

Zhou

2018

Oncol Rep

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The present study aimed to investigate the association between the expression of ZEB1 and LAMA4 in gastric cancer and the possible underlying mechanisms of this. In addition, the present study also investigated the prognostic value of LAMA4 in gastric cancer. LAMA4, MMP2, MMP9 and ZEB1 expression and their associations were analyzed by data mining in The Cancer Genome Atlas‑stomach adenocarcinoma (TCGA‑STAD). Overall survival (OS) curves of patients with gastric cancer were generated using data from TCGA and Kaplan‑Meier plotting. Gastric cancer HGC‑27 and SGC‑7901 cell lines were used as in vitro cell models to assess the effect of LAMA4 on cell migration and invasion and to study the regulatory effect of ZEB1 on LAMA4 expression. The results of the present study indicated that LAMA4 upregulation was associated with higher grade tumors. LAMA4‑knockdown significantly reduced MMP2 expression in gastric cancer cells and impaired the speed of wound healing and the invasive capability of the cancer cells. ZEB1 was strongly co‑expressed with LAMA4 in TCGA‑STAD (Pearson's r=0.85). Induced ZEB1 expression significantly increased LAMA4 expression at the mRNA and protein level in HGC‑27 and SGC‑7901 cells. A dual‑luciferase assay confirmed that ZEB1 directly binded to the promoter of LAMA4. High LAMA4 expression independently predicted a poor OS (HR, 1.614; 95% CI, 1.155‑2.256; P=0.005) in patients with primary gastric cancer. These results indicated that ZEB1 was able to epigenetically activate LAMA4 expression via binding to its promoter in gastric cancer cells. High LAMA4 expression was an independent indicator of a poor OS in patients with gastric cancer.

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Clinical significance of zinc-finger E-box binding homeobox 1 mRNA levels in peritoneal washing for gastric cancer

Cited by 11 publications

References 36 publications

Interaction between Wnt/β-catenin pathway and microRNAs regulates epithelial-mesenchymal transition in gastric cancer (Review)

Interaction between Wnt/β-catenin pathway and microRNAs regulates epithelial-mesenchymal transition in gastric cancer (Review)

Prognostic Significance of Molecular Analysis of Peritoneal Fluid for Patients with Gastric Cancer: A Meta-Analysis

LAMA4 expression is activated by zinc finger E‑box‑binding homeobox�1 and independently predicts poor overall survival in gastric cancer

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