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| Content Provider | Springer Nature : BioMed Central |
|---|---|
| Author | Lei, Ruixue Zhao, Yanteng Huang, Kai Wang, Qian Wan, Kangkang Li, Tingting Yang, Haijun Lv, Xianping |
| Abstract | Background Methylated SDC2 and TFPI2 are widely used for colorectal cancer (CRC) detection. However, they often miss some CRCs, which directly diminishes the sensitivity. Further investigations of the underlying mechanisms leading to the missed samples will facilitate developing more eligible methylation markers. Methods CRC samples from TCGA and GEO datasets were divided into three groups, High-methylation/ High-methylation (HH), High-methylation/Low-methylation (HL), and Low-methylation/Low-methylation (LL) according to the methylation status of SDC2 and TFPI2 promoters. Variations in age, tumor location and microsatellite instable were then assessed between the three groups and verified in our custom cohort. Results Samples of HL group preferred to derive from left-sided CRCs (P < 0.05). HH samples showed the highest microsatellite instability and mutation load (mean nonsynonymous mutations for HH/HL/LL: 10.55/3.91/7.02, P = 0.0055). Almost all mutations of BRAF, one of the five typical CpG island methylator phenotype (CIMP) related genes, were observed in HH group (HH/HL/LL: 51/0/1, P = 0.018). Besides, older patients were frequently found in HH group. Expression analysis identified 37, 84, and 22 group-specific differentially expressed genes (DEGs) for HH, HL, and LL, respectively. Functional enrichment analysis revealed that HH-specific DEGs were mainly related to transcription regulation, while LL-specific DEGs were enriched in the biological processes of extracellular matrix interaction and cell migration. Conclusions The current study revealed that the performance of methylation-based markers might be affected by tumor location, patient age, mutation load and MSI, and these respective sides should be considered when developing new methylation markers for CRC detection. |
| Related Links | https://bmcgastroenterol.biomedcentral.com/counter/pdf/10.1186/s12876-022-02175-3.pdf |
| Ending Page | 13 |
| Page Count | 13 |
| Starting Page | 1 |
| File Format | HTM / HTML |
| DOI | 10.1186/s12876-022-02175-3 |
| Journal | BMC Gastroenterology |
| Issue Number | 1 |
| Volume Number | 22 |
| Language | English |
| Publisher | BioMed Central |
| Publisher Date | 2022-02-28 |
| Access Restriction | Open |
| Subject Keyword | Gastroenterology Internal Medicine Hepatology SDC2 TFPI2 Colorectal cancer Methylation Phenotypes |
| Content Type | Text |
| Resource Type | Article |
| Subject | Gastroenterology |
| Journal Impact Factor | 2.5/2023 |
| 5-Year Journal Impact Factor | 2.7/2023 |
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