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P58 - Tumor Biology and Systems Biology - Basic and Translational Science - Epigenomics (ID 196)
- Event: WCLC 2020
- Type: Posters
- Track: Tumor Biology and Systems Biology - Basic and Translational Science
- Presentations: 1
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
P58.03 - Investigation on the Role of Methylation in Field Cancerization of Non-Small Cell Lung Cancer (ID 1320)
00:00 - 00:00 | Presenting Author(s): Qiushi Wang
Non-small cell lung cancer (NSCLC) is a complex malignancy that develops through progressive pathologic changes driven by an interplay of a variety of molecular pathways including both genetic and epigenetic mechanisms. Aberrant DNA methylation has been implicated in early cancer development; however, studies on its role in field cancerization are limited. Field cancerization, also referred to as pre-malignant field defect, is the process in which a population of normal or pre-malignant cells is affected by oncogenic alterations leading to progressive molecular changes that drive their malignancy. In our study, we aimed to identify tumor-specific methylation patterns that could distinguish between pre-malignant lesions and tumor tissues and could potentially be developed as biomarkers.Methods
A total of 52 Chinese patients with early-stage resectable NSCLC were included in the study. Blood, surgically-resected tumor, tumor-adjacent normal and tumor-distant normal tissue samples were obtained from all the patients. Methylation levels from all samples were profiled using targeted bisulfite sequencing using custom-designed lung-cancer methylation panel covering 80,672 CpG sites, spanning 1.05 mega bases of the human genome. To improve the linkage of methylation sites, we further analyzed the methylation profile as methylation blocks.Results
We have analyzed a total of 205 tissue and blood samples from 52 patients with early-stage NSCLC. Principal component analysis demonstrated the distinct methylation profile of tumor tissues as compared to both adjacent and distant histologically-normal tissues. Meanwhile, tumor-adjacent and -distant normal tissues had similar methylation levels. A total of 5,080 tumor-specific methylation blocks, including 4,660 hypermethylated and 420 hypomethylated blocks, spanning 2,013 genes were found to be differentially methylated in tumor tissues as compared to tumor-distant normal tissues (P<0.05). Of the top 15 tumor-specific hypermethylated blocks, 85% were associated with cancer development. Furthermore, analysis of the methylation profile between peri-operative and post-operative blood samples revealed a significant reduction in the level of tumor-specific hypermethylated blocks (P<0.001). In order to further identify aberrant methylation during different steps of cancer development, we compared the methylation profiles among the tumor, tumor-adjacent and -distant normal tissues. A total of 694 methylation blocks were found to be differentially methylated among the three tissue types, indicating pre-malignant field-related methylation patterns. The methylation levels from 659 blocks were lower in tumor-distant normal tissues as compared to tumor-adjacent normal tissues and also lower between adjacent normal and tumor tissues. Meanwhile, methylation levels from 35 blocks were higher in tumor-distant normal tissues than adjacent normal tissues and tumor tissues. Further analysis revealed that these differentially methylated blocks were enriched with transcription factor genes, suggesting the role of epigenetic regulation of transcription factors as a key step in driving malignancy and field cancerization.Conclusion
Our data revealed distinct methylation patterns between pre-malignant lesions and malignant tumors, suggesting the essential role of DNA methylation as an early step in pre-malignant field defects. Moreover, our study also identified cancer-specific methylation blocks that could potentially be used as markers for lung cancer screening.
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