The overexpression of MDM4: an effective and novel predictor of gastric adenocarcinoma lymph node metastasis

Bao, Junjie; Nanding, Abiyasi; Song, Haibin; Xu, Rui; Qu, Guofan; Xue, Yingwei

doi:10.18632/oncotarget.11971

Cited by 12 publications

(23 citation statements)

References 29 publications

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“…Gurzu et al found that VEGF, a gene increases the likelihood of tumor invasion and LMN in GC, is overexpressed in younger patients with GC 17. Bao et al argued that MDM4, which is related to LNM and a poor prognosis in GC, is overexpressed in younger patients compared with older patients 18. Based on the abovementioned studies and the results of our study, we hypothesized that age is closely associated with LNM in GC.…”

Section: Discussionsupporting

confidence: 62%

Higher Risk of Lymph Node Metastasis in Young Patients with Early Gastric Cancer

Wang

et al. 2019

J. Cancer

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Objective: Whether age affects lymph node metastasis (LNM) in patients with gastric cancer (GC) is currently inconclusive. This study investigates the effect of age on LNM in patients with GC. Methods: From January 1988 to December 2013, 22,808 GC patients underwent gastrectomy at the Surveillance, Epidemiology, and End Results database were included. The relationship between age and LNM was analyzed. Results: The median number of examined lymph nodes (ELNs) was 12 (interquartile range [IQR], 7-20) among the 22,808 patients with GC, and the median numbers of ELNs were 10 (IQR, 5-18), 12 (IQR, 6-19), 13 (IQR, 7-21) and 13 (IQR, 7-21) in patients with T1 to T4 disease, respectively. A total of 13,780 (60.4%) patients presented with LNM. The LNM rates were 69.6%, 66.1%, 64.7%, 61.8%, 57.8% and 55.6% for patients in the 20-39, 40-49, 50-59, 60-69, 70-79 and ≥ 80 age groups, respectively (P < 0.001). The LNM rates and the number of positive lymph nodes were correlated with age among patients whose diseases were of the same T stage (all P < 0.01). Multivariate analysis showed that age was an independent predictor for LNM in patients with early gastric cancer (EGC) (P < 0.05), and linear regression analysis showed that the LNM rate was higher in young patients with EGC (P < 0.05). Conclusions: Age is an independent predictor for LNM in EGC. Moreover, LNM is more common in young patients with EGC than in other age groups, which indicates that limited lymph node dissection may not be appropriate for young patients with EGC.

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Section: Discussionsupporting

confidence: 62%

Higher Risk of Lymph Node Metastasis in Young Patients with Early Gastric Cancer

Wang

et al. 2019

J. Cancer

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“…The overexpression of MDMX has been found in 36.6% gastric cancer and contributes to lymph node metastasis (68,69). Although MDMX overexpression can influence the prognosis of gastric cancer, it cannot be used as an independent prognostic factor for this disease (69). The amplification and overexpression of MDMX have also been observed in bladder cancer and has been implicated in high-grade and invasive disease (70).…”

Section: Amplification and Overexpression Of Mdmx In Human Cancer Andmentioning

confidence: 99%

Section: Amplification and Overexpression Of Mdmx In Human Cancer Andmentioning

confidence: 99%

Targeting MDMX for Cancer Therapy: Rationale, Strategies, and Challenges

et al. 2020

Front. Oncol.

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The oncogene MDMX, also known as MDM4 is a critical negative regulator of the tumor suppressor p53 and has been implicated in the initiation and progression of human cancers. Increasing evidence indicates that MDMX is often amplified and highly expressed in human cancers, promotes cancer cell growth, and inhibits apoptosis by dampening p53-mediated transcription of its target genes. Inhibiting MDMX-p53 interaction has been found to be effective for restoring the tumor suppressor activity of p53. Therefore, MDMX is becoming one of the most promising molecular targets for developing anticancer therapeutics. In the present review, we mainly focus on the current MDMX-targeting strategies and known MDMX inhibitors, as well as their mechanisms of action and in vitro and in vivo anticancer activities. We also propose other potential targeting strategies for developing more specific and effective MDMX inhibitors for cancer therapy.

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“…Additionally, MDM4 plays an essential role in MDM2‐MDM4‐p53 regulatory circuit to enhance the function of the E3 ubiquitin ligase of MDM2 and promoting degradation of p53 . Therefore, either downexpression or overexpression of MDM4 gene may affect cancer risk and prognosis . The translational potential of MDM4 for predicting survival has become a novel therapeutic target for p53 reactivation in cancer treatment …”

Section: Introductionmentioning

confidence: 99%

“…33 Therefore, either downexpression or overexpression of MDM4 gene may affect cancer risk and prognosis. 34,35 The translational potential of MDM4 for predicting survival has become a novel therapeutic target for p53 reactivation in cancer treatment. 26 Recent studies suggested that the variation in the 3′-untranslated region (3′-UTR) of MDM4 can lead to a decreased risk of various malignancies.…”

Section: Introductionmentioning

confidence: 99%

A genetic variant within MDM4 3′UTR miRNA binding site is associated with HPV16‐positive tumors and survival of oropharyngeal cancer

Zhang

Wei

Liu

et al. 2019

Molecular Carcinogenesis

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As MDM4 and HPV16 E6 oncoproteins play important roles in inhibition of p53 activity, a functional polymorphism (rs4245739) in the 3’ UTRs of MDM4 targeted by miRNA-191 may alter its expression level or functional efficiency, thus affecting tumor status and survival in HPV-positive squamous cell carcinoma of oropharynx (SCCOP). A total of 564 incident SCCOP patients with definitive radiotherapy were included for determination of tumor HPV16 status and genotypes of the polymorphism. Univariate and multivariable Cox models were performed to assess the associations between the polymorphism and outcomes. We found that MDM4 rs4245739 had statistically significant associations with tumor HPV-positivity and survival of SCCOP patients. Patients with AC/CC variant genotypes of MDM4 rs4245739 were approximately 3-fold more likely to be HPV16-positive tumors among SCCOP patients compared with common homozygous AA genotype (aOR, 3.2, 95%CI, 1.9–5.5). Moreover, patients with MDM4 rs4245739 AC/CC variant genotypes had significantly better overall, disease-specific, and disease-free survival compared with those with the corresponding common homozygous AA genotype (all log-rank: P < 0.05); and these genotypes were significantly associated with an approximately 3 to 4 times reduced risk of overall death, death owing to disease, and recurrence after multivariable adjustment. Finally, the significant effects of MDM4 rs4245739 polymorphism on survival were found among HPV16-positive SCCOP patients only after the stratified analyses by tumor HPV status. We concluded that MDM4 rs4245739 polymorphism is significantly associated with tumor HPV status and survival of SCCOP, especially in HPV16-positive SCCOP patients treated with definitive radiotherapy; nevertheless, prospective larger studies are warranted.

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The overexpression of MDM4: an effective and novel predictor of gastric adenocarcinoma lymph node metastasis

Cited by 12 publications

References 29 publications

Higher Risk of Lymph Node Metastasis in Young Patients with Early Gastric Cancer

Higher Risk of Lymph Node Metastasis in Young Patients with Early Gastric Cancer

Targeting MDMX for Cancer Therapy: Rationale, Strategies, and Challenges

A genetic variant within MDM4 3′UTR miRNA binding site is associated with HPV16‐positive tumors and survival of oropharyngeal cancer

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