基于 DNA 甲基化的有丝分裂衰老指数在口腔癌发生和复发中的作用。
Role of DNA methylation-based mitotic ageing indices in oral cancer development and recurrence.
发表日期:2023 Oct 16
作者:
Srikant Ambatipudi, Mayuri Inchanalkar, Manoj B Mahimkar
来源:
ORAL DISEASES
摘要:
DNA 甲基化数据可用于从复杂组织中得出有丝分裂指数。在这里,我们评估了 DNA 甲基化衍生的有丝分裂衰老指数是否与口腔鳞状细胞癌 (OSCC) 的发展和无复发生存 (RFS) 相关。基于 DNA 甲基化的有丝分裂指数(MitoticAge、TNSC 和 hyperSC)是使用算法导出的“MitoticAge”和“epiTOC2”用于发现[非恶性 (n = 22)、癌前 (n = 22) 和 OSCC (n = 68) 组织] 和验证数据集(GSE87053、GSE136704 和 TCGA-HNSCC)。评估了非恶性、癌前和 OSCC 组织之间有丝分裂指数的差异。最后,评估了 OSCC 中估计的有丝分裂指数与 RFS 之间的关联。在发现和验证数据集中,与非恶性和癌前口腔组织相比,在 OSCC 中观察到有丝分裂老化增加。 HPV 阳性 HNSCC 具有较高的有丝分裂指数 TNSC。有丝分裂年龄指数hypoSC 与OSCC 的RFS 相关(p = 0.011,HR 2.61,95% CI 1.24-5.48)。DNA 甲基化衍生的有丝分裂指数与OSCC 的发展和RFS 相关。因此,DNA甲基化衍生的有丝分裂指数可能是一种有价值的研究工具,可以可靠地估计恶性和非恶性口腔组织中干细胞分裂的累积数量。未来的研究利用有丝分裂指数来预测 OSCC 的临床结果是有必要的。© 2023 Wiley periodicals LLC。
DNA methylation data can be used to derive mitotic indices from complex tissues. Here, we assessed if the DNA methylation-derived mitotic ageing indices are associated with oral squamous cell carcinoma (OSCC) development and recurrence-free survival (RFS).DNA methylation-based mitotic indices (MitoticAge, TNSC and hypoSC) were derived using algorithms "MitoticAge" and "epiTOC2" for the discovery [non-malignant (n = 22), premalignant (n = 22) and OSCC (n = 68) tissues] and validation datasets (GSE87053, GSE136704 and TCGA-HNSCC). Differences in mitotic indices between non-malignant, premalignant and OSCC tissues were assessed. Finally, the association between estimated mitotic indices and RFS was evaluated in OSCCs.In the discovery and validation datasets, increased mitotic ageing was observed in OSCC compared to non-malignant and premalignant oral tissues. HPV-positive HNSCCs had higher mitotic index TNSC. Mitotic age index hypoSC was associated with RFS in OSCC (p = 0.011, HR 2.61, 95% CI 1.24-5.48).DNA methylation-derived mitotic indices are associated with OSCC development and RFS. Thus, DNA methylation-derived mitotic indices may be a valuable research tool to reliably estimate the cumulative number of stem cell divisions in malignant and non-malignant oral tissues. Future research utilizing mitotic indices for predicting clinical outcomes in OSCC is warranted.© 2023 Wiley Periodicals LLC.