DNA methylation genome-wide analysis in remnant and primary gastric cancers

Sugimoto, Kiichi; Ito, Tomoaki; Hulbert, Alicia; Chen, Chen; Orita, Hajime; Mizumoto, Hiroshi; Fukagawa, Takeo; Katai, Hitoshi; Wada, Ryo; Sato, Koichi; Sakamoto, Kazuhiro; Yu, Wayne; Considine, Michael; Cope, Leslie; Brock, Malcolm V.

doi:10.1007/s10120-019-00949-5

Cited by 6 publications

(6 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition to esophageal carcinoma, abnormal expression of EPB41L3 has been reported in other common digestive system cancer types, including gastric cancer, intestinal carcinoma, colorectal cancer, hepatocellular carcinoma and pancreatic carcinoma (71-75). Consistent with previous findings that Helicobacter pylori (HP)-induced inflammatory response promotes EPB41L3 DNA methylation, the methylation of EPB41L3 is significantly lower in remnant gastric cancers with the decline of HP infection following distal gastrectomy (73,74). In colorectal cancer, protein 4.1B/DAL-1 has been shown to be downregulated through membrane proteomic analysis (72).…”

Section: Meningiomas a Loss Of Protein 41b/dal-1 Occurs In ≥50%supporting

confidence: 84%

Pivotal roles of protein 4.1B/DAL‑1, a FERM‑domain containing protein, in tumor progression (Review)

et al. 2019

View full text Add to dashboard Cite

Protein 4.1B/DAL-1, encoded by erythrocyte membrane protein band 4.1-like 3 (EPB41L3), belongs to the protein 4.1 superfamily, a group of proteins that share a conserved four.one-ezrin-radixin-moesin (FERM) domain. Protein 4.1B/DAL-1 serves a crucial role in cytoskeletal organization and a number of processes through multiple interactions with membrane proteins via its FERM, spectrin-actin-binding and C-terminal domains. A number of studies have indicated that a loss of EPB41L3 expression is commonly observed in lung cancer, breast cancer, esophageal squamous cell carcinoma and meningiomas. DNA methylation and a loss of heterozygosity have been reported to contribute to the downregulation of EPB41L3. To date, the biological functions of protein 4.1B/DAL-1 in carcinogenesis remain unknown. The present review summarizes the current understanding of the role of protein 4.1B/DAL-1 in cancer and highlights its potential as a cancer diagnostic and prognostic biomarker in cancer therapeutics. Contents 1. Introduction 2. Structural characteristics of the protein 4.1 superfamily 3. Functional roles of individual domains of protein 4.1B/ DAL-1 4. Relevance of protein 4.1B/DAL-1 in cancer 5. Future directions 6. Conclusions

show abstract

Section: Meningiomas a Loss Of Protein 41b/dal-1 Occurs In ≥50%supporting

confidence: 84%

Pivotal roles of protein 4.1B/DAL‑1, a FERM‑domain containing protein, in tumor progression (Review)

et al. 2019

View full text Add to dashboard Cite

show abstract

“…In patients with GC, previous studies have revealed that DNA methylation could serve as molecular biomarkers in helicobacter pylori infection, cancer occurrence, and prognosis (10). Meanwhile, with the rapid development of highthroughput sequencing, genome-wide profiling provides us more individualized and systematic evaluation of DNA methylation in cancer (11,12). However, the molecular mechanisms underlying gene-expression regulated by DNA methylation is unclear, and the diagnostic and prognostic value of these DNA methylation-driven gene remains to be future explored.…”

Section: Introductionmentioning

confidence: 99%

A Prognostic Nomogram Model Based on mRNA Expression of DNA Methylation-Driven Genes for Gastric Cancer

Chen

Liu

et al. 2020

Front. Oncol.

View full text Add to dashboard Cite

PurposeThe exploration and interpretation of DNA methylation-driven genes might contribute to molecular classification, prognostic prediction and therapeutic choice. In this study, we built a prognostic risk model via integrating analysis of the transcriptome and methylation profile for patients with gastric cancer (GC).MethodsThe mRNA expression profiles, DNA methylation profiles and corresponding clinicopathological information of 415 GC patients were downloaded from The Cancer Genome Atlas (TCGA). Differential expression and correlation analysis were performed to identify DNA methylation-driven genes. The candidate genes were selected by univariate Cox regression analyses followed by the least absolute shrinkage and selection operator (LASSO) regression. A prognostic risk nomogram model was then built together with clinicopathological parameters.Results5 DNA methylation-driven genes (CXCL3, F5, GNAI1, GAMT and GHR) were identified by integrated analyses and selected to construct the prognostic risk model with clinicopathological parameters. High expression and low DNA hypermethylation of F5, GNAI1, GAMT and GHR, as well as low expression and high DNA hypomethylation of CXCL3 were significantly associated with poor prognosis rates, respectively. The high-risk group showed a significantly shorter prognosis than the low-risk group in the TCGA dataset (HR = 0.212, 95% CI = 0.139–0.322, P = 2e-15). The final nomogram model showed high predictive efficiency and consistency in the training and validation group.ConclusionWe construct and validate a prognostic nomogram model for GC based on five DNA methylation-driven genes with high performance and stability. This nomogram model might be a powerful tool for prognosis evaluation in the clinic and also provided novel insights into the epigenetics in GC.

show abstract

“…Due to low levels of DNA methylation, replicates for some samples had no detectable methylation, as anticipated. Methylation was quantified using the Relative Methylation Value (RMV), based on calculation of 2 -ΔΔCt for each detectable replicate compared to the mean Ct for β-actin (ACTB) (22,23). The bisulfite-modified DNA was assessed for CHFR-promoter methylation with 200 nM forward primer, 5'-GTT ATT TTC GTG ATT CGT AGG CGA C-3', 200 nM reverse primer, 5'-CGA AAC CGA AAA TAA CCC GCG-3', and 80 nM probe, 5'-\56-FAM\ CGC TCG ACC \ZEN\ ATC TTT AAT CCT AAC CAA ACG ACT TC \3IABkFQ\-3'.…”

Section: Methodsmentioning

confidence: 99%

“…For non-detectable replicates, a Ct of 100 was used to give a near zero value for 2 -ΔΔCt . The mean 2 -ΔΔCt value (RMV) was calculated as: mean 2 -ΔΔCt (RMV)=(2 -ΔΔCt_replicate_1 +2 -ΔΔCt_replicate_2 +2 -ΔΔCt_replicate_3 )/3 (22,23).…”

Section: Methodsmentioning

confidence: 99%

CHFR-Promoter-Methylation Status Is Predictive of Response to Irinotecan-based Systemic Chemotherapy in Advanced Colorectal Cancer

Hagiwara¹,

Sugimoto²,

Momose³

et al. 2022

Anticancer Res

Self Cite

View full text Add to dashboard Cite

Background/Aim: We investigated whether promoter methylation of the checkpoint-with-forkhead-andring-finger-domains (CHFR) gene is a predictor of the efficacy of irinotecan-based systemic chemotherapy for advanced colorectal cancer (CRC) patients. Materials and Methods: CHFR-promoter methylation was measured by quantitative methylation-specific PCR (qMSP). The histoculture drug response assay (HDRA) was used in vitro to analyze the correlation between CHFR-promoter methylation and the efficacy of the irinotecan-active-metabolite SN38 in colorectalcancer tissues from 44 CRC patients. CHFR promotermethylation was also analyzed for its correlation with clinical response to irinotecan-based systemic chemotherapy of 49 CRC patients. Results: CHFR-promoter methylation significantly-positively correlated with inhibition of colon cancer by SN38 in the HDRA (p=0.002). CHFR-promoter methylation also significantly-positively correlated with clinical response to irinotecan-based systemic chemotherapy (p=0.04 for disease control). CHFR-promoter methylation also significantly-positively correlated (p=0.01) with increased progression-free survival for patients treated with irinotecan-containing FLOFIRI in combination with bevacizumab, the most-frequent regimen in the cohort. Conclusion: Sensitivity of advanced CRC patients to irinotecan-based systemic chemotherapy can be predicted by the extent of CHFR-promoter methylation.Colorectal cancer (CRC) is the third most-common malignancy and the second-most-frequent cause of cancerrelated mortality worldwide (1). Recent advances in systemic chemotherapy have improved post-operative outcomes in advanced or metastatic CRC (2, 3). The current first-line therapies for unresectable CRC are oxaliplatinum-based and irinotecan-based regimens. The response rates (RR) are approximately 40-60% for these regimens (4, 5), with time to progression (TTP) of 7-8 months and median overall survival (OS) of 14-21 months (6). The two drugs are equivalent in efficacy in this clinical setting (7). Oxaliplatinum causes severe chronic neurotoxicity, which limits the duration of treatment (8). Therefore, irinotecanbased therapy is often preferred for advanced or metastatic CRC. However, there is currently no established biomarker that is predictive of the clinical benefit of irinotecan-based systemic chemotherapy (9).DNA methylation is altered in human cancer as originally discovered by Hoffman et al. (10). DNA methylation is involved in the development and progression of CRC (11,12). DNA methylation of tumor-suppressor genes is useful as a prognostic and susceptibility factor to anti-cancer drugs (13,14). Recently, checkpoint-with-fork-head-and-ringfinger-domains (CHFR)-promoter methylation has been suggested to be associated with favorable treatment 697 This article is freely accessible online.

show abstract

DNA methylation genome-wide analysis in remnant and primary gastric cancers

Cited by 6 publications

References 49 publications

Pivotal roles of protein 4.1B/DAL‑1, a FERM‑domain containing protein, in tumor progression (Review)

Pivotal roles of protein 4.1B/DAL‑1, a FERM‑domain containing protein, in tumor progression (Review)

A Prognostic Nomogram Model Based on mRNA Expression of DNA Methylation-Driven Genes for Gastric Cancer

CHFR-Promoter-Methylation Status Is Predictive of Response to Irinotecan-based Systemic Chemotherapy in Advanced Colorectal Cancer

Contact Info

Product

Resources

About