論文 - 詳細
| RRC ID | 52135 |
|---|---|
| 著者 | Yokoi K, Yamashita K, Ishii S, Tanaka T, Nishizawa N, Tsutsui A, Miura H, Katoh H, Yamanashi T, Naito M, Sato T, Nakamura T, Watanabe M. |
| タイトル | Comprehensive molecular exploration identified promoter DNA methylation of the CRBP1 gene as a determinant of radiation sensitivity in rectal cancer. |
| ジャーナル | Br J Cancer |
| Abstract |
BACKGROUND:Neoadjuvant chemoradiotherapy (NCRT) for advanced rectal cancer (RC) is a well-evidenced therapy; however, some RC patients have no therapeutic response. Patient selection for NCRT so that non-responsive patients are excluded has been subjective. To date, no molecular markers indicating radiation sensitivity have been reported. METHODS:We irradiated six colorectal cancer (CRC) cell lines and identified HCT116 cells as radiation-sensitive and HCT15 and DLD-1 cells as radiation resistant. Using a microarray, we selected candidate radiation sensitivity marker genes by choosing genes whose expression was consistent with a radiation-resistant or sensitive cell phenotype. RESULTS:Among candidate genes, cellular retinol binding protein 1 (CRBP1) was of particular interest because it was not only induced in HCT116 cells by tentative 10 Gy radiation treatments, but also its expression was increased in HCT116-derived radiation-resistant cells vs parental cells. Forced expression of CRBP1 decreased the viability of both HCT15 and DLD-1 cells in response to radiation therapy. We also confirmed that CRBP1 was epigenetically silenced by hypermethylation of its promoter DNA, and that the quantitative methylation value of CRBP1 significantly correlated with histological response in RC patients with NCRT (P=0.031). CONCLUSIONS:Our study identified CRBP1 as a radiation-sensitive predictor in RC. |
| 巻・号 | 116(8) |
| ページ | 1046-1056 |
| 公開日 | 2017-4-11 |
| DOI | 10.1038/bjc.2017.65 |
| PII | bjc201765 |
| PMID | 28291773 |
| PMC | PMC5396119 |
| MeSH | Biomarkers, Tumor / genetics* Blotting, Western Cell Proliferation DNA Methylation* Gene Expression Regulation, Neoplastic / radiation effects* Humans Oligonucleotide Array Sequence Analysis Prognosis Promoter Regions, Genetic / genetics* RNA, Messenger / genetics Radiation Tolerance / genetics* Real-Time Polymerase Chain Reaction Rectal Neoplasms / genetics* Rectal Neoplasms / pathology Rectal Neoplasms / radiotherapy Retinol-Binding Proteins, Cellular / genetics* Retinol-Binding Proteins, Cellular / metabolism Reverse Transcriptase Polymerase Chain Reaction Tumor Cells, Cultured |
| IF | 5.791 |
| 引用数 | 8 |
| リソース情報 | |
| ヒト・動物細胞 | HCT116(RCB2979) COLO-320(RCB1193) LoVo(RCB1639) |