Association between SOX17, Wif-1 and RASSF1A promoter methylation status and response to chemotherapy in patients with metastatic gastric cancer

Karamitrousis, Evangelos; Balgkouranidou, Ioanna; Xenidis, Nikolaos; Amarantidis, Kyriakos; Biziota, Eirini; Koukaki, Triantafyllia; Trypsianis, Grigorios; Karayiannakis, Anastasios J.; Bolanaki, Helen; Chatzaki, Εkaterini; Kolios, George; Lianidou, Evi; Lambropoulou, María; Kakolyris, Stylianos

doi:10.1515/cclm-2020-0662

Cited by 4 publications

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“…In recent years, multiple studies have suggested a key role of abnormal methylation of certain genes in the occurrence and development of GC. DNA methylation analysis could provide information for early screening, efficacy, and prognostic assessment of patients with GC ( 16 , 17 ) and other types of cancer ( 18 ). Patients with widespread gene hypermethylation show a lower overall survival rate, suggesting a correlation between gene methylation and chemotherapy sensitivity ( 18 , 19 ).…”

Section: Introductionmentioning

confidence: 99%

Predictive value of DNA methylation in the efficacy of chemotherapy for gastric cancer

Li,

Mo,

Yang

et al. 2023

Front. Oncol.

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BackgroundGastric cancer (GC) is one of the most common causes of cancer-related death. Drug resistance in chemotherapy often occurs in patients with GC, leading to tumor recurrence and poor survival. DNA methylation is closely related to the development of cancer.MethodsTo investigate the role of DNA methylation in chemotherapy resistance in GC patients, we conducted a comprehensive analysis using DNA methylation data and survival information obtained from The Cancer Genome Atlas. Univariate Cox analysis was performed to screen for differential DNA methylation of chemotherapy response in patients who did and did not receive chemotherapy. Multivariate Cox analysis was then performed to identify the independent prognostic genes. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were used to explore the biological function of the signature genes.ResultsPatients receiving adjuvant chemotherapy for GC survived longer. 308 differentially methylated genes were demonstrated to be associated with prognosis. Six genes were optimally chosed for establisehing the risk model, including C6orf222, CCNL1, CREBZF, GCKR, TFCP2, and VIPR2. It was constructed based on the DNA methylation levels of these six genes: risk score = 0.47123374*C6orf222 + 9.53554803*CCNL1 + 10.40234138* CREBZF + 0.07611856* GCKR + 18.87661557*TFCP2 − 0.46396254* VIPR2. According to the risk score, patients receiving chemotherapy were divided into high- and low-risk groups, and the prognosis of the two groups was compared. The high-risk group had a shorter survival; however, this association was not present in patients without chemotherapy. The accuracy and predictive efficacy of the risk score in predicting the 1-, 3-, and 5-year survival of patients was evaluated with the receiver operating characteristic curve. In patients receiving chemotherapy, the area under the curve of the risk score for 1-, 3-, and 5-year survival was 0.841, 0.72, and 0.734, respectively. In patients who did not receive chemotherapy, the area under the curve was 0.406, 0.585, and 0.585, respectively. A nomogram model was constructed based on the risk score and clinical indicators. The model showed good consistency in the predicted probabilities and actual probabilities. Gene Ontology functional enrichment of these candidate methylated genes showed the following molecular functions: RNA binding, protein binding, mRNA binding, and nucleic acid binding; that they were mediated mainly through the following cell components: nuclear speck, nucleoplasm, nucleus, catalytic step 2 spliceosome, and the transcription factor AP-1 complex; and that they were involved in the following biological processes: mRNA processing, mRNA splicing, and RNA polymerase II promoter transcription. The Kyoto Encyclopedia of Genes and Genomes pathway enrichment results revealed that the signaling pathways mainly enriched were transcriptional misregulation in cancer, spliceosome, and the IL-17 signaling pathway.ConclusionOur work identifies a six DNA methylated expression signature as a promising biomarker of chemo-resistance in GC, which provides new insights into the development of new strategies to overcome chemo-resistance in GC.

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Section: Introductionmentioning

confidence: 99%

Predictive value of DNA methylation in the efficacy of chemotherapy for gastric cancer

Li,

Mo,

Yang

et al. 2023

Front. Oncol.

View full text Add to dashboard Cite

show abstract

“…Methylation of the promoter region of PD-L1 gene causes an overexpression of PD-L1 in prostate cancer and glioblastoma patients, leading to a more aggressive disease prognosis [6,7] . In addition, the methylation of the promoter region of several genes (e.g., SOX-17, Wif-1, RASSF1A) can lead to a decrease in progression-free survival (PFS) and overall survival (OS), as well as a decrease in the response to chemotherapy in patients with metastatic gastric adenocarcinoma [8,9] .…”

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confidence: 99%