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Wild-Type TP53 Predicts Poor Prognosis in Patients with Gastric Cancer.

ABSTRACT: TP53 gene is often mutated in gastric cancer (GC), nonetheless its relationship with clinicopathological characteristics and prognosis is still unclear. Here, we sought to ascertain the difference in clinical phenotypes between TP53 wild-type and mutant tumors in confirmed gastric cancer patients. To this end, we analyzed TP53 mutation status of 415 TCGA GC patients in relation to their clinical and pathological features as well as prognosis. Longrank Test showed that the survival rate of gastric cancer patients with TP53 WT was significantly lower than that of TP53 mut. Compared with TP53 mut gastric cancer patients with low mRNA expression, TP53 WT patients with low mRNA expression have lower overall survival rate. The death risk of TP53 WT gastric cancer patients is 1.395 times that of TP53 mut gastric cancer patients. The death risk of TP53 mut gastric cancer patients is not related to age, and advanced age is not a risk factor. However, the death risk of TP53 WT patients with gastric cancer increases with age, and the death risk of patients over 70 years old is 1.899 times that of patients under 60 years old. These results suggest that the prognosis of elderly gastric cancer patients with TP53 WT is worse.

Conclusion

our results indicate that the status of TP53 mutation in GC is significantly correlated with clinical or molecular categories and that the prognosis of GC patients with WT TP53 is worse than that of patients with mutant TP53. Therefore, our data emphasize the importance of distinguishing TP53 WT to predict poor overall survival and relapse-free survival in patients with GC.

SUBMITTER: Deng W

PROVIDER: S-EPMC8694034 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature

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Wild-Type TP53 Predicts Poor Prognosis in Patients with Gastric Cancer.

Deng Wenhong W Hao Qiongyu Q Vadgama Jaydutt J Wu Yong Y

Journal of cancer science and clinical therapeutics 20210301 1

TP53 gene is often mutated in gastric cancer (GC), nonetheless its relationship with clinicopathological characteristics and prognosis is still unclear. Here, we sought to ascertain the difference in clinical phenotypes between TP53 wild-type and mutant tumors in confirmed gastric cancer patients. To this end, we analyzed TP53 mutation status of 415 TCGA GC patients in relation to their clinical and pathological features as well as prognosis. Longrank Test showed that the survival rate of gastri ...[more]

PMID: 34950877

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Project description:The switching/sucrose non-fermenting (SWI/SNF) chromatin remodeling complexes use the energy of ATP hydrolysis to remodel nucleosomes and modulate transcription, which plays an important role in tumors by regulating epigenetics. SWI/SNF Related, Matrix Associated, Actin Dependent Regulator of Chromatin, Subfamily C, Member 1 (SMARCC1) has dual roles in tumors but its role in gastric cancer remains unclear. This study was aimed to find the role of SMARCC1 in gastric cancer. SMARCC1 expression across various tumors from The Cancer Genome Atlas was analyzed using TIMER 2.0 (http://timer.comp-genomics.org/). SMARCC1 mRNA expression profiles in gastric cell lines and gastric tissues were compared with normal tissues and analyzed in the Cancer Cell Line Encyclopedia, Oncomine, and Gene Expression Omnibus databases. SMARCC1 mRNA and protein were then examined in fresh gastric cancer tissues and compared with adjacent normal tissues using quantitative real-time PCR, western blotting, and immunohistochemistry. Associations between SMARCC1 expression and clinicopathological factors, overall survival, and disease-free survival were further evaluated using 130 gastric cancer samples harvested from patients after radical total gastrectomy or subtotal gastrectomy at the Xiangya Hospital of Central South University (Changsha, China). SMARCC1 was frequently upregulated in gastric cancer cells and tissues. SMARCC1 overexpression was significantly associated with tumor size (P=0.002), differentiation (P=0.006), depth of invasion (P=0.001), lymph node involvement (P=0.016), and TNM stage (P=0.007). Furthermore, univariate and multivariate Cox analysis revealed that high SMARCC1 expression, depth invasion, lymph node involvement, and TNM stage were independent risk factors for both overall and disease-free survival in gastric cancer patients (all P<0.05). Kaplan-Meier survival analysis revealed that high SMARCC1 expression predicted poor prognosis in gastric cancer patients (P<0.01). High SMARCC1 expression contributes to poor prognosis in gastric cancer patients. SMARCC1 may be a prognostic biomarker and therapeutic target in gastric cancer.

Project description:BackgroundThrombospondins (THBSs) are a family of multidomain and secreted matricellular Ca(2+)-binding glycoproteins which has at least five members encoded by independent genes. As a THBSs family member, Thrombospondin2 (THBS2) has been reported to regulate angiogenesis. Nevertheless, the functions and clinical significance of THBS2 still remains unclear in gastric cancer.MethodsThe mRNA and protein expression levels of THBS2 were assessed in 14 paired of gastric cancer specimens and corresponding normal mucosas using quantitative real-time PCR and western blot analysis. Immunohistochemistry of THBS2 and CD34 on population-based tissue microarrays consisting of 129 gastric cancer cases were used to evaluate the prognostic significance of THBS2 and microvessel density (MVD) of each sample. Survival analyses were performed by Kaplan-Meier method and Cox's proportional hazards model. Colony formation assay, endothelial cell tube formation assay, cell migration assay and apoptosis analysis in MKN-45 and SGC-7901 cell lines were carried out to evaluate the effects of THBS2 on gastric cancer in vitro.Results85.71% (12 of 14) gastric cancer tissues expressed remarkably lower THBS2 in both mRNA and protein levels than the corresponding normal controls. Consistently, tissue microarray (TMA) results showed THBS2 levels were also inhibited in gastric cancer tissues compared with the normal controls. Moreover, we observed that patients with higher levels of THBS2 were significantly correlated with more favourable prognosis while decreased THBS2 expression were associated with poorer histological grades of gastric cancer. Additionally, our in vitro experiments further demonstrated that overexpression of THBS2 could impede both the proliferation rate and the tube formation of Human umbilical vein endothelial cells (HUVECs) in MKN-45 and SGC-7901 cell lines.ConclusionOur study suggests THBS2 is aberrantly expressed in gastric cancer and plays a critical role in cancer progression, which can be a potential prognosis predictor of gastric cancer.

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Wild-Type TP53 Predicts Poor Prognosis in Patients with Gastric Cancer.

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Wild-Type TP53 Predicts Poor Prognosis in Patients with Gastric Cancer.

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