Genome-wide analysis identifies critical DNA methylations within NTRKs genes in colorectal cancer.
Genome-wide analysis identifies critical DNA methylations within NTRKs genes in colorectal cancer.
复制标题
全基因组分析识别结直肠癌中 NTRKs 基因内的关键 DNA 甲基化。
DOI：
10.1186/s12967-021-02740-6
复制
发表时间：
2021-02-16
影响因子：
7.4
通讯作者：
Yu H
中科院分区：
文献类型：
--
作者：
Chen Z;Huang Z;Luo Y;Zou Q;Bai L;Tang G;Wang X;Cao G;Huang M;Xiang J;Yu H
神经营养性原肌球蛋白受体激酶（NTRKs）是一类基因家族，在不同的癌症中作为癌基因或抑癌基因发挥作用。本研究旨在探讨NTRKs基因在结直肠癌中的甲基化、表达及预后价值。对CRC患者的DNA甲基化和表达谱进行分析，以探索NTRKs基因内的关键甲基化。在回顾性收集的229例CRC患者队列中验证了甲基化标志物，并在TCGA的其他肿瘤类型中进行了测试。DNA甲基化状态通过定量甲基化特异性PCR（QMSP）测定。6个结直肠癌队列的基因组学特征显示，与正常粘膜相比，结直肠癌中NTRKs基因启动子更频繁地甲基化，这与基因表达抑制有关。我们在NTRK 3启动子内发现了一个由cg 27034819和cg 11525479靶向的特异性甲基化区域，该区域最能预测CRC的生存结局。NTRK 3启动子甲基化显示了验证队列中生存结局的独立预测值（P = 0.004，HR 2.688，95% CI [1.355，5.333]）。基于此，开发了预测生存结局的列线图，C指数为0.705。此外，增加NTRK 3启动子甲基化改善了目前使用的预后模型的性能（AIC：516.49 vs 513.91; LR：39.06 vs 43.64，P = 0.032）。最后，NTRK 3启动子甲基化也预测了其他肿瘤的生存率，包括胰腺癌、胶质母细胞瘤和胃腺癌。这项研究强调了NTRK 3甲基化在预后评估中的重要价值，以及改善CRC和其他肿瘤当前预后模型的潜力。
Neurotrophic tropomyosin receptor kinases (NTRKs) are a gene family function as oncogene or tumor suppressor gene in distinct cancers. We aimed to investigate the methylation and expression profiles and prognostic value of NTRKs gene in colorectal cancer (CRC). An analysis of DNA methylation and expression profiles in CRC patients was performed to explore the critical methylations within NTRKs genes. The methylation marker was validated in a retrospectively collected cohort of 229 CRC patients and tested in other tumor types from TCGA. DNA methylation status was determined by quantitative methylation-specific PCR (QMSP). The profiles in six CRC cohorts showed that NTRKs gene promoter was more frequently methylated in CRC compared to normal mucosa, which was associated with suppressed gene expression. We identified a specific methylated region within NTRK3 promoter targeted by cg27034819 and cg11525479 that best predicted survival outcome in CRC. NTRK3 promoter methylation showed independently predictive value for survival outcome in the validation cohort (P = 0.004, HR 2.688, 95% CI [1.355, 5.333]). Based on this, a nomogram predicting survival outcome was developed with a C-index of 0.705. Furthermore, the addition of NTRK3 promoter methylation improved the performance of currently-used prognostic model (AIC: 516.49 vs 513.91; LR: 39.06 vs 43.64, P = 0.032). Finally, NTRK3 promoter methylation also predicted survival in other tumors, including pancreatic cancer, glioblastoma and stomach adenocarcinoma. This study highlights the essential value of NTRK3 methylation in prognostic evaluation and the potential to improve current prognostic models in CRC and other tumors.
登录
查看更多内容
影响因子：
4.6
作者：
Cho YA;Chung JM;Ryu H;Kim EK;Cho BC;Yoon SO
通讯作者：
Yoon SO
DOI：
10.6004/jnccn.2020.0032
发表时间：
2020-07-01
影响因子：
13.4
作者：
Benson, Al B., III;Venook, Alan P.;Gurski, Lisa A.
通讯作者：
Gurski, Lisa A.
影响因子：
3.4
作者：
Kamiya, A.;Inokuchi, M.;Kojima, K.
通讯作者：
Kojima, K.
FOLFOX辅助化疗的III期结直肠癌的预后可以通过分子亚型进行预测。
影响因子：
--
作者：
Kwon Y;Park M;Jang M;Yun S;Kim WK;Kim S;Paik S;Lee HJ;Hong S;Kim TI;Min B;Kim H
通讯作者：
Kim H
影响因子：
4.5
作者：
Luo Y;Kaz AM;Kanngurn S;Welsch P;Morris SM;Wang J;Lutterbaugh JD;Markowitz SD;Grady WM
通讯作者：
Grady WM