Review: Gastric malignancies: Basic aspects

Camargo, M. Constanza; Figueiredo, Céu; Machado, José Carlos

doi:10.1111/hel.12642

Cited by 18 publications

(16 citation statements)

References 42 publications

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“…Although surgery-based therapeutic approaches can improve the long-term survival of patients with early-stage GC, the 5-year survival rate of patients with advancedstage GC is low because of the lack of effective treatments. 2 Therefore, studies aimed at understanding the molecular mechanism regulating GC and identifying novel and suitable therapeutic targets for the treatment of this disease are urgently needed.…”

Section: Introductionmentioning

confidence: 99%

<p>PKMYT1 Promotes Gastric Cancer Cell Proliferation and Apoptosis Resistance</p>

Zhang

Chen

Liu

et al. 2020

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Background: Abnormal expression of protein kinase membrane associated tyrosine/threonine 1 (PKMYT1) is closely associated with multiple types of cancers. In the present study, we examined the roles of PKMYT1 in gastric cancer (GC) progression. Methods: We examined the expression status of PKMYT1 in GC tissues and cell lines. Meanwhile, short hairpin RNA (shRNA) was used to inhibit the endogenous expression of PKMYT1 in GC cells. Then we analyzed the effect of PKMYT1 on the malignant biological behavior of GC cells by in vitro and in vivo experiments. Results: The findings showed high PKMYT1 expressions in GC tissues as well as a positive correlation between PKMYT1 expression and prognosis of patients with GC. Additional findings also revealed that PKMYT1 silencing significantly enhanced apoptosis and inhibited GC cell proliferation. In vivo, the silence of PKMYT1 inhibits tumor growth. Further analysis showed that the increase in PKMYT1 expressions led to malignant biological behavior through activation of the MAPK signaling pathway. Conclusion: Our data suggested that PKMYT1 promotes cell proliferation and apoptosis resistance in GC cells by activating the MAPK signaling pathway, making it a potential therapeutic target for GC.

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Section: Introductionmentioning

confidence: 99%

<p>PKMYT1 Promotes Gastric Cancer Cell Proliferation and Apoptosis Resistance</p>

Zhang

Chen

Liu

et al. 2020

OTT

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“…Gastric cancer (GC) is one of the most malignant and prevalent tumors, with poor prognosis worldwide (1,2). Although clinical therapeutic methods and medical technology have improved (surgical resection and target drug therapy, for example), the 5 year survival rates of GC still remain dismal (3).…”

Section: Introductionmentioning

confidence: 99%

PLXNC1 Enhances Carcinogenesis Through Transcriptional Activation of IL6ST in Gastric Cancer

et al. 2020

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Background: Transcriptional factors (TFs) are responsible for orchestrating gene transcription during cancer progression. However, their roles in gastric cancer (GC) remain unclear.Methods: We analyzed the differential expressions of TFs and, using GC cells and tissues, investigated plexin C1 (PLXNC1) RNA levels, as well as PLXNC1's clinical relevance and functional mechanisms. The molecular function of PLXNC1 was evaluated in vitro and in vivo. Kaplan-Meier curves and the log-rank test were used to analyze overall survival (OS) and disease-free survival (DFS).Results: PLXNC1 was frequently up-regulated in GC and associated with poor prognosis. The expression level of PLXNC1 could serve as an independent biomarker to predict a patient's overall survival. Notably, knockdown of PLXNC1 significantly abolished GC cell proliferation, and migration, and overexpression of PLXNC1 accelerated carcinogenesis in GC. The gene set enrichment analysis (GSEA) indicated that high-expression of PLXNC1 was positively correlated with the activation of epithelial-mesenchymal transition (EMT), TNF-α, and IL-6/STAT3 signaling pathways. PLXNC1 promoted proliferation and migration of GC cells through transcriptional activation of the interleukin 6 signal transducer (IL6ST), which could rescue the malignant behavior of PLXNC1-deficient GC cells. Conclusions:Our study demonstrated that the PLXNC1 plays an oncogenic role in GC patients. The PLXNC1-IL6ST axis represents a novel potential therapeutic target for GC.

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“…Gastric cancer is the third deadliest cancer in the world and the absolute number of cases is increasing every year due to aging and growing of high-risk populations [1]. Geographically, about 43% of total global cases are concentrated in China [2] and its mortality remains the third among all human cancers in China [3].…”

Section: Introductionmentioning

confidence: 99%

Genetic polymorphisms in folate-metabolizing genes associated with gastric cancer prognosis in northwest China subjects

et al. 2020

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Influence of folate metabolism has long been studied in cancer and copies evidences have suggested that the key genes involved were correlated with GC risk and prognosis. However, their genetically association and contribution for GC prognosis are still elusive. To evaluate the effect of folate metabolism related genes polymorphisms on the prognosis of gastric cancer (GC), the genotype of seven single nucleotide polymorphisms (SNPs) of three genes were selected and genotyped in a cohort of 664 GC patients, including genes of Methylenetetrahydrofolate reductase (MTHFR), Methionine synthase reductase (MTRR), and Methionine synthase (MTR). Kaplan-Meier Curve, long-rank tests and multivariate Cox proportional hazard model were used for prognosis analysis. The results demonstrated that TT or CT/TT genotypes of SNP rs1532268 in MTRR gene coding region are significantly associated with a poorer overall survival (OS) when compared with CC genotype (HR=2.340, 95% CI: 1.240-4.414, p=0.009; or HR=1.502, 95% CI: 1.083-2.085, p=0.015, respectively). Furthermore, comparing to that of the CC genotype, the detrimental effect of rs1532268 TT genotype was also evident in the special subgroups of GC patients, especially in patients with BMI<24 and H. pylori infection. Moreover, significant association between increased relapse and TT genotype of rs1532268 was also observed in patients who are females, BMI<24 and without chemotherapy. In addition, the joint analysis demonstrated that integration of rs1532268 genotypes and BMI, H. pylori infection status, clinical stage and tumor site may significantly improve the predictive abilities for predicting OS of GC patients. In conclusion, it suggested that the MTRR rs1532268 polymorphism is significantly associated with clinical outcomes of GC patients, especially in those with lower BMI (BMI<24) or positive H. pylori infection status, which warrants further validation. And the polymorphism of MTRR rs1532268 may be a potential prognostic factor for GC patients.

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Review: Gastric malignancies: Basic aspects

Cited by 18 publications

References 42 publications

<p>PKMYT1 Promotes Gastric Cancer Cell Proliferation and Apoptosis Resistance</p>

<p>PKMYT1 Promotes Gastric Cancer Cell Proliferation and Apoptosis Resistance</p>

PLXNC1 Enhances Carcinogenesis Through Transcriptional Activation of IL6ST in Gastric Cancer

Genetic polymorphisms in folate-metabolizing genes associated with gastric cancer prognosis in northwest China subjects

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