Gastric cancer is a heterogeneous disease encompassing diverse morphological (intestinal versus diffuse) and molecular subtypes (MSI, EBV, TP53 mutation).
We found that the cyclin-dependent kinase inhibitor 2A (<i>p16</i>), E-cadherin (<i>CDH1</i>), runt-related transcription factor 3 (<i>RUNX3</i>), human mutL homolog 1 (<i>MLH1</i>), RAS association domain family protein 1A (<i>RASSF1A</i>), cyclin-dependent kinase inhibitor 2B (<i>p15</i>), adenomatous polyposis coli (<i>APC</i>), Glutathione S-transferase P1 (<i>GSTP1</i>), TP53 dependent G2 arrest mediator candidate (<i>Reprimo</i>), and O6-methylguanine-DNAmethyl-transferase (<i>MGMT</i>) promoter methylation was notably higher in blood samples of patients with GC compared with non-tumor controls.
A case-control study was performed using 46 patients: 15 EBVaGC and 31 EBV-negative GC (EBVnGC) cases. p53 expression was detected by immunohistochemistry (IHC), the evaluation of p53 mRNA levels was performed by RT-qPCR and TP53 mutations were investigated only in EBVaGC cases using the DNA sanger sequencing method. p53 expression was found in 97.8% (45/46) of all gastric cancer cases (including EBVaGC and EBVnGC groups).
It was further revealed that gastric cancer with negative CDX2 expression is associated with negative p53 staining, and this association was particularly significant in undifferentiated gastric cancer.
We investigated the clinical significance of ARID1A protein expression in gastric cancer (GC), and examined its association with Epstein-Barr virus-associated (EBV) GC, mismatch repair (MMR) deficiency, and p53 alteration.
Our study aimed to investigate the regulation of ubiquitin protein ligase E3 component n-recognin 2 (UBR2) enriched in exosomes secreted by p53 deficient mouse bone marrow MSC (p53<sup>-/-</sup> mBMMSC) in gastric cancer progression in vivo and in vitro.
Nevertheless, some autoantibodies, such as anti-MAGEA4, anti-CTAG1 or anti-TP53 and their combinations could possibly contribute to the development of cancer early detection tests (not necessarily restricted to gastric cancer) when being combined with other markers.
The present study analyzed the relationship between TP53 codon 72 polymorphisms and the clinical outcome of advanced gastric cancer patients receiving capecitabine plus paclitaxel chemotherapy.
The cancer cell fraction assessed by the panel of the three genes showed good correlation with that assessed by the TP53 mutant allele frequency in 13 GCs (r = 0.77).
Our data suggest that GC with TP53 mutations seems to develop as differentiated histologic type and show aggressive biological behavior such as venous invasion.
Combined analysis showed that subjects carrying the miR-34b/c rs4938723 CT/CC and TP53 CG/CC genotypes had a 0.62-fold decreased risk to develop gastric cancer compared with subjects carrying the miR-34b/c rs4938723 TT and TP53 CG/CC genotypes (OR=0.62; 95% CI, 0.40-0.96).
Our results showed tissue p53 overexpression in patients with gastric cancer to be associated with poor prognosis in terms of overall survival (HR, 1.610; 95% CI, 1.394 -5.235; p: <0.001).
Overall, 78% of GC cases harbored one clinically relevant GA or more, with the most frequent alterations being found in TP53 (50%), ARID1A (24%), KRAS (16%), CDH1 (15%), CDKN2A (14%), CCND1 (9.5%), ERBB2 (8.5%), PIK3CA (8.6%), MLL2 (6.9%), FGFR2 (6.0%), and MET (6.0%).
TP53 mutation, allelic deletion of the APC gene and nuclear staining of β-catenin are frequently detected in the intestinal phenotype of GC, whereas CDH1 gene mutation, microsatellite instability and DNA hypermethylation of MLH1 are common events in the gastric phenotype of GC.
In this work, we analyzed the association of SNPs in P53 (rs1042522), MDM2 (rs2279744), MDM4 (rs1380576) and Hausp (rs1529916) genes with gastric cancer in a hospital-based Chinese Han population (642 cases and 720 cancer-free controls).
Mdm2 binds to the amino-terminus of p53 to induce its degradation and a single nucleotide polymorphism in the MDM2 promoter region (T309G) has been reported to increase the risk of several carcinomas, such as gastric cancer.
In conclusion, this study revealed that p53 codon 72 polymorphism and dietary and tobacco habit interactions influence stomach cancer development in Mizoram, India.
Further, we identified increased protein expression of Mdm2/x, both powerful regulators of p53, in 100% of the IM+GC cohort with these samples also exhibiting high levels of wild-type p53 protein.