Comprehensive Analysis of LINE-1 Methylation Level and Tumor Immunity in Esophageal Cancer

2019 ◽  
Vol 70 (2) ◽  
pp. 182-183
Author(s):  
Y. Baba ◽  
H. Baba
Keyword(s):  
Esophageal Cancer ◽  
Tumor Immunity ◽  
Methylation Level ◽  
Comprehensive Analysis

PS02.176: LINE-1 METHYLATION LEVEL AND LOCAL IMMUNE RESPONSE IN ESOPHAGEAL CANCER

2018 ◽  
Vol 31 (Supplement_1) ◽  
pp. 172-172
Author(s):  
Yoshifumi Baba ◽  
Taisuke Yagi ◽  
Yuki Kiyozumi ◽  
Yukiharu Hiyoshi ◽  
Masaaki Iwatsuki ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Immune Response ◽  
Esophageal Cancer ◽  
Methylation Level ◽  
Cpg Island ◽  
Surrogate Marker ◽  
Esophageal Tumor ◽  
Local Immune Response ◽  
Dna Hypomethylation ◽  
Response Status

Abstract Background In cancer cells, DNA methylation may be altered in two principle ways; global DNA hypomethylation and site-specific CpG island promoter hypermethylation. Since Long interspersed element-1 (LINE-1 or L1; a repetitive DNA retrotransposon) constitutes a substantial portion (approximately 17%) of the human genome, the extent of LINE-1 methylation is regarded as a surrogate marker of global DNA methylation. In previous studies, we demonstrated that LINE-1 hypomethylation was strongly associated with a poor prognosis in esophageal cancer, supporting its potential role as a prognostic marker (Ann Surg 2012). We also found that LINE-1-hypomethylated tumors showed highly frequent genomic gains at various loci containing candidate oncogenes such as CDK6 (Clin Cancer Res 2014). Given that immunotherapy, as represented by PD-1/PD-L1-targeting antibodies, has increasingly gained attention as a novel treatment strategy for esophageal cancer, better understanding of local immune response status in esophageal cancer is important. The aim of this study is to evaluate the relationship between LINE-1 methylation level and local immune response in esophageal cancer. Methods Using a non-biased database of 305 curatively resected esophageal cancers, we evaluated PD-L1 expression and TIL status (CD8 expression) by immunohistochemical analysis (Ann Surg 2017). Results TIL positivity was significantly correlated with longer overall survival (log-rank P < 0.0001). TIL-negative cases demonstrated significantly lower LINE-1 methylation level compared with TIL-positive cases (P = 0.012). This finding certainly supports that LINE-1 methylation level may influence the local immune response status. Conclusion PD-L1 expression was not related with LINE-1 methylation level. Further investigations in this field would provide deeper insights into esophageal tumor immunology and assist the development of new therapeutic strategies against esophageal cancer. Disclosure All authors have declared no conflicts of interest.

The association between smoking and LINE-1 hypomethylation (global DNA hypomethylation) in normal esophageal epithelium of patients with esophageal squamous cell carcinoma.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 41-41
Author(s):  
Shiro Iwagami ◽  
Yoshifumi Baba ◽  
Masayuki Watanabe ◽  
Hironobu Shigaki ◽  
Keisuke Miyake ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Squamous Cell Carcinoma ◽  
Esophageal Cancer ◽  
Squamous Cell ◽  
Methylation Level ◽  
Continuous Variable ◽  
Smoking History ◽  
Esophageal Mucosa ◽  
Esophageal Epithelium ◽  
Dna Hypomethylation

41 Background: DNA methylation is a major epigenetic mechanism in X-chromosome inactivation, imprinting and repression of transposable elements and endogenous retroviral sequences. Global DNA hypomethylation appears to play an important role in genomic instability, leading to cancer development. DNA methylation in the long interspersed nucleotide element-1, L1 (LINE-1) repetitive element is a good indicator of global DNA methylation level. Smoking and alcohol is extremely important as the etiology of esophageal squamous cell carcinoma. Nonetheless, whether or not smoking and alcohol affect LINE-1 methylation level in normal esophageal epithelium of esophageal cancer patients remains uncertain. Methods: We quantified LINE-1 methylation of normal esophageal mucosa using pyrosequencing technology in 118 resected esophageal squamous cell carcinomas. The data on smoking (Brinkman index, absence or presence) and alcohol amount are available in all cases. We excluded preoperatively treated cases. Results: LINE-1 methylation in normal esophageal epithelium of esophageal cancer patients ranged from 57.1 to 92.8 of 0-100 scale (N=118; mean 81.2; median 80.0; standard deviation 7.2). LINE-1 methylation level (continuous variable) was significantly associated with Brickman index (continuous variable) (r=0.12, p=0.0002); heavy smoker had lower LINE-1 methylation level of normal esophageal mucosa. LINE-1 methylation level was lower in patients with smoking history (mean 79.7) than in patients without smoking history (mean 83.2) (p=0.034). Alcohol assumption was not associated with LINE-1 methylation level (r=0.003, p=0.58). Conclusions: Smoking was associated with LINE-1 hypomethylation in esophageal normal epithelium, suggesting the possibility of epigenetic field effects caused by cigarette in esophageal tumorigenesis. Considering that DNA methylation alterations are reversible and can thus be targets for chemoprevention, our findings may have clinical implication.

scholarly journals Detection of esophageal cancer patients using circulating serum microRNA from the result of comprehensive analysis

2017 ◽  
Vol 28 ◽  
pp. v35-v36
Author(s):  
K. Kato ◽  
K. Sudo ◽  
N. Boku ◽  
S. Abe ◽  
Y. Saito ◽  
...  
Keyword(s):  
Esophageal Cancer ◽  
Cancer Patients ◽  
Comprehensive Analysis ◽  
Serum Microrna

scholarly journals Comprehensive Analysis of Tumor-Infiltrating Immune Cells and Relevant Therapeutic Strategy in Esophageal Cancer

2020 ◽  
Vol 2020 ◽  
pp. 1-12 ◽  
Author(s):  
Guangrong Lu ◽  
Liping Chen ◽  
Shengjie Wu ◽  
Yuao Feng ◽  
Tiesu Lin
Keyword(s):  
Esophageal Cancer ◽  
Immune Cells ◽  
Immune Cell ◽  
Risk Model ◽  
Risk Group ◽  
Tumor Stage ◽  
Tumor Location ◽  
High Risk Group ◽  
Comprehensive Analysis ◽  
Lasso Regression

A growing body of evidence has indicated that behaviors of cancers are defined by not only intrinsic activities of tumor cells but also tumor-infiltrating immune cells (TIICs) in the tumor microenvironment. However, it still lacks a well-structured and comprehensive analysis of TIICs and its therapeutic value in esophageal cancer (EC). The proportions of 22 TIICs were evaluated between 150 normal tissues and 141 tumor tissues of EC by the CIBERSORT algorithm. Besides, correlation analyses between proportions of TIICs and clinicopathological characters, including age, gender, histologic grade, tumor location, histologic type, LRP1B mutation, TP53 mutation, tumor stage, lymph node stage, and TNM stage, were conducted. We constructed a risk score model to improve prognostic capacity with 5 TIICs by least absolute shrinkage and selection operator (lasso) regression analysis. The risk score=−1.86∗plasma+2.56∗T cell follicular helper−1.37∗monocytes−3.64∗activated dendritic cells−2.24∗resting mast cells (immune cells in the risk model mean the proportions of immune cell infiltration in EC). Patients in the high-risk group had significantly worse overall survival than these in the low-risk group (HR: 2.146, 95% CI: 1.243-3.705, p=0.0061). Finally, we identified Semustine and Sirolimus as two candidate compounds for the treatment of EC based on CMap analysis. In conclusion, the proportions of TIICs may be important to the progression, prognosis, and treatment of EC.

Tumor Long-interspersed Nucleotide Element-1 Methylation Level and Immune Response to Esophageal Cancer

2019 ◽  
Vol 272 (6) ◽  
pp. 1025-1034 ◽  
Author(s):  
Keisuke Kosumi ◽  
Yoshifumi Baba ◽  
Kazuo Okadome ◽  
Taisuke Yagi ◽  
Yuki Kiyozumi ◽  
...  
Keyword(s):  
Immune Response ◽  
Esophageal Cancer ◽  
Methylation Level

Prognostic significance of LINE-1 methylation level in esophageal squamous cell carcinoma.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 26-26 ◽  
Author(s):  
Yoshifumi Baba ◽  
Shiro Iwagami ◽  
Masayuki Watanabe ◽  
Hironobu Shigaki ◽  
Satoshi Ida ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Squamous Cell Carcinoma ◽  
Esophageal Cancer ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Methylation Level ◽  
Prognostic Significance ◽  
Esophageal Mucosa ◽  
Dna Hypomethylation

26 Background: Genome-wide DNA hypomethylation plays a role in genomic instability and carcinogenesis. DNA methylation in the long interspersed nucleotide element-1, L1 (LINE-1) repetitive element is a good indicator of global DNA methylation level. LINE-1 methylation is a useful marker for predicting cancer prognosis and monitoring efficacy of adjuvant therapy. Esophageal squamous cell carcinoma, the major histological type of esophageal cancer in East Asian countries, is one of the most aggressive malignant tumors. Nonetheless, prognostic significance of LINE-1 hypomethylaiton in esophageal cancer remains uncertain. Methods: Using 217 curatively resected esophageal squamous cell carcinomas, we quantified LINE-1 methylation using bisulfite-PCR-pyrosequencing assay. Cox proportional hazards model was used to calculate mortality hazard ratio (HR), adjusted for clinical, epidemiologic, and pathological variables. Results: Esophageal cancers showed significantly lower LINE-1 methylation level compared to matched normal esophageal mucosa (p<0.0001; N=50). Tumoral LINE-1 methylation ranged from 24.8 to 91.8 of 0-100 scale (N=217; mean 64.5; median 65.0; standard deviation 12.8). LINE-1 hypomethylation was significantly associated with disease-free survival [log-rank p=0.0008; univariate HR= 2.31, 95% confidence interval (CI) 1.38-3.84, p=0.0017; multivariate HR=1.81, 95% CI 1.06-3.05, p=0.031] and overall survival (log-rank p=0.0013; univariate HR=2.21, 95% CI 1.33-3.60, p=0.0026; multivariate HR=1.87, 95% CI 1.12-3.08, p=0.018]. Conclusions: LINE-1 hypomethylation in esophageal cancer is associated with shorter survival, suggesting its role as a prognostic biomarker. Given that epigenetic changes, including DNA methylation alterations, are reversible and can thus be targets for therapy or chemoprevention, our findings may have considerable clinical implications.

Discovery and validation of methylation signatures in circulating cell-free DNA for early detection of esophageal cancer: A case-control study.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16027-e16027
Author(s):  
Weitao Zhuang ◽  
Xiao-song Ben ◽  
Chengcheng Li ◽  
Jiayue Xu ◽  
Dan Tian ◽  
...  
Keyword(s):  
Esophageal Cancer ◽  
Early Detection ◽  
Methylation Level ◽  
Early Stage ◽  
Precancerous Lesions ◽  
Esophageal Disease ◽  
Esophageal Tumor ◽  
Esophageal Diseases ◽  
Circulating Free Dna ◽  
Free Dna

e16027 Background: The pivotal goal of esophageal cancer (ESCA) screening is to identify early-stage cancer or precancerous lesions when curable treatments are available. Methylation of circulating-free DNA (cfDNA) has shown promising results in the early detection of multiple tumors recently. Here we conducted a prospective study to investigate the performance of cfDNA methylation in the early detection of ESCA. Methods: Specific methylation markers for ESCA were identified and optimized based on 24 esophageal tumor and its corresponding adjacent tissues. Age-matched participants with ESCA (n = 136), benign esophageal disease (n = 21) and healthy controls (n = 126) were randomized into the training and testing sets to develop an early-detection classifier. Results: In total, 921 differentiated methylation blocks (DMBs) between tumor and adjacent tissues were identified, of which 679 (73.7%) showed higher methylation level and 242 (26.3%) had lower methylation level in tumor tissues. In the training set, the specificity of the model built with these DMBs was 94.1% (95% CI, 85.5%−98.4%) and the sensitivity was 86.0% (95% CI, 72.2%−94.8%). The sensitives increased with stages, which were 77.8% (95% CI, 39.8%−97.2%), 90.9% (95% CI, 58.7%−99.8%), 83.3% (95% CI, 51.7%−97.9%) and 100.0% (95%CI, 63.1%−100.0%) for stage I-IV, respectively. Similar results were observed in the testing set with area under curve (AUC) of 0.932 (95% CI, 0.887−0.977). Conclusions: The cfDNA methylation profiles distinguished ESCAs from healthy individuals and benign esophageal diseases with promising sensitivity and specificity. Consideration of the potential value of early detection in ESCAs, further evaluation in larger prospective studies is warranted.

Considerations in Dysphagia Management Following Esophagectomy

2016 ◽  
Vol 1 (13) ◽  
pp. 169-176
Author(s):  
Lisa M. Evangelista ◽  
James L. Coyle
Keyword(s):  
Esophageal Cancer ◽  
Minimally Invasive ◽  
Minimally Invasive Surgical Procedures ◽  
Esophageal Resection ◽  
Minimally Invasive Surgical ◽  
Operative Complications ◽  
Swallowing Difficulties ◽  
Epidemiological Impact ◽  
Invasive Techniques ◽  
Management Of Dysphagia

Esophageal cancer is the sixth leading cause of death from cancer worldwide. Esophageal resection is the mainstay treatment for cancers of the esophagus. While curative, surgical resection may result in swallowing difficulties that require intervention from speech-language pathologists (SLPs). Minimally invasive surgical procedures for esophageal resection have aimed to reduce morbidity and mortality associated with more invasive techniques. Both intra-operative and post-operative complications, regardless of the surgical approach, can result in dysphagia. This article will review the epidemiological impact of esophageal cancers, operative complications resulting in dysphagia, and clinical assessment and management of dysphagia pertinent to esophageal resection.

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