Concomitant PIK3CA amplification and RASSF1A or PAX6 hypermethylation predict worse survival in gastric cancer

Yang, Qi; Shao, Yuan; Shi, Jing; Qu, Yiping; Wu, Kexia; Dang, Siwen; Shi, Bingyin; Hou, Peng

doi:10.1016/j.clinbiochem.2013.10.014

Cited by 20 publications

(13 citation statements)

References 34 publications

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“…To the best of our knowledge, this is the first study suggesting this association in breast cancer, and no other study is available for direct comparison. A previous study in gastric cancer showed that methylation of the PAX6 promoter was associated with reduced survival (18). Another study in gastric cancer showed that PAX6 was associated with markers of a poor prognosis, such as lymph node metastasis (19).…”

Section: Discussionmentioning

confidence: 99%

PAX6 overexpression is associated with the poor prognosis of invasive ductal breast cancer

et al. 2015

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Abstract. Paired box 6 (PAX6) plays a significant role in the development of human neuroectodermal epithelial tissues. Previous studies have suggested that the PAX6 promoter is hypermethylated in breast cancer and that it is involved in breast cancer cell proliferation. The present study aimed to investigate the expression of PAX6 in invasive breast cancer tissues, and to evaluate its prognostic significance. Immunohistochemistry (IHC) was used to detect PAX6 expression on a breast cancer tissue microarray containing tissues from 111 patients. Associations of PAX6 expression with staging and prognosis were analyzed. PAX6 was mainly expressed in the nucleus. The PAX6 staining intensity was not associated with age, histological grade, lymph node status, tumor size, or progesterone receptor and human epidermal growth factor receptor 2 expression (all P>0.05). A high level of PAX6 staining was more frequent in estrogen receptor (ER)-negative cases compared with ER-positive cases (43.9 vs. 25.7%; P= 0.049). After a median follow-up time of 110 months, the patients with low PAX6 expression exhibited an improved survival rate compared with the patients with high PAX6 expression (P<0.001). Cox analysis showed a worse survival rate in the patients with high PAX6 staining (hazard ratio, 3.458; 95% confidence interval, 1.575-7.593; P= 0.002). In conclusion, high tumor PAX6 staining intensity by IHC was associated with a poor prognosis in breast cancer patients.

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Section: Discussionmentioning

confidence: 99%

PAX6 overexpression is associated with the poor prognosis of invasive ductal breast cancer

et al. 2015

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“…47 Furthermore, PIK3CA amplification notably influenced the overall prognosis in GC regardless of early or late stage tumors, suggesting that this genetic event has an important role in the multistep process of gastric carcinogenesis. 48,49 Taken together, PIK3CA may function as a GC driver with independent prognostic significance.…”

Section: Gc Involves Cnvs and Other Genetic Aberrationsmentioning

confidence: 97%

Gastric cancer and gene copy number variation: emerging cancer drivers for targeted therapy

Liang

2015

Oncogene

128

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Gastric cancer (GC) is among the most common malignancy in the world with poor prognosis and limited treatment options. It has been established that gastric carcinogenesis is caused by a complex interaction between host and environmental factors. Copy number variation (CNV) refers to a form of genomic structural variation that results in abnormal gene copy numbers, including gene amplification, gain, loss and deletion. DNA CNV is an important influential factor for the expression of both protein-coding and non-coding genes, affecting the activity of various signaling pathways. CNV arises as a result of preferential selection that favors cancer development, and thus, targeting the amplified 'driver genes' in GC may provide novel opportunities for personalized therapy. The detection of CNVs in chromosomal or mitochondrial DNA from tissue or blood samples may assist the diagnosis, prognosis and targeted therapy of GC. In this review, we discuss the recent CNV discoveries that shed light on the molecular pathogenesis of GC, with a specific emphasis on CNVs that display diagnostic, prognostic or therapeutic significances in GC.

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“…ID4 promoter methylation was also correlated with the risk of prostate cancer [44,45]. Meanwhile, NOL4, PAX6, TRIM58, and ZNF382 promoter methylation was also associated with the occurrence of many cancers [46][47][48][49][50][51][52][53][54][55]. Figure 4: Kaplan-Meier survival curves for overall survival outcomes according to the risk cuto point for prognostic hypermethylated/ hypomethylated genes.…”

Section: Discussionmentioning

confidence: 98%

Combined Analysis of the Aberrant Epigenetic Alteration of Pancreatic Ductal Adenocarcinoma

Huang

et al. 2019

BioMed Research International

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Background. Pancreatic ductal adenocarcinoma (PDAC) remains one of the most fatal malignancies due to its high morbidity and mortality. DNA methylation exerts a vital part in the development of PDAC. However, a mechanistic role of mutual interactions between DNA methylation and mRNA as epigenetic regulators on transcriptomic alterations and its correlation with clinical outcomes such as survival have remained largely uncovered in cancer. Therefore, elucidation of aberrant epigenetic alteration in the development of PDAC is an urgent problem to be solved. In this work, we conduct an integrative epigenetic analysis of PDAC to identify aberrant DNA methylation-driven cancer genes during the occurrence of cancer. Methods. DNA methylation matrix and mRNA profile were obtained from the TCGA database. The integration of methylation and gene expression datasets was analyzed using an R package MethylMix. The genes with hypomethylation/hypermethylation were further validated in the Kaplan–Meier analysis. The correlation analysis of gene expression and aberrant DNA methylation was also conducted. We performed a pathway analysis on aberrant DNG methylation genes identified by MethylMix criteria using ConsensusPathDB. Results. 188 patients with both methylation data and mRNA data were considered eligible. A mixture model was constructed, and differential methylation genes in normal and tumor groups using the Wilcoxon rank test was performed. With the inclusion criteria, 95 differential methylation genes were detected. Among these genes, 74 hypermethylation and 21 hypomethylation genes were found. The pathway analysis revealed an increase in hypermethylation of genes involved in ATP-sensitive potassium channels, Robo4, and VEGF signaling pathways crosstalk, and generic transcription pathway. Conclusion. Integrated analysis of the aberrant epigenetic alteration in pancreatic ductal adenocarcinoma indicated that differentially methylated genes could play a vital role in the occurrence of PDAC by bioinformatics analysis. The present work can help clinicians to elaborate on the function of differentially methylated expressed genes and pathways in PDAC. CDO1, GJD2, ID4, NOL4, PAX6, TRIM58, and ZNF382 might act as aberrantly DNA-methylated biomarkers for early screening and therapy of PDAC in the future.

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Concomitant PIK3CA amplification and RASSF1A or PAX6 hypermethylation predict worse survival in gastric cancer

Cited by 20 publications

References 34 publications

PAX6 overexpression is associated with the poor prognosis of invasive ductal breast cancer

PAX6 overexpression is associated with the poor prognosis of invasive ductal breast cancer

Gastric cancer and gene copy number variation: emerging cancer drivers for targeted therapy

Combined Analysis of the Aberrant Epigenetic Alteration of Pancreatic Ductal Adenocarcinoma

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