Boughanem Hatim, Martin-Nuñez Gracia María, Torres Esperanza, Arranz-Salas Isabel, Alcaide Julia, Morcillo Sonsoles, Tinahones Francisco J, Crujeiras Ana B, Macias-Gonzalez Manuel
Department of Endocrinology and Nutrition, Virgen de la Victoria University Hospital, Institute of Biomedical Research in Malaga (IBIMA), University of Malaga, 29016 Malaga, Spain.
CIBER in Physiopathology of Obesity and Nutrition (CIBEROBN), Instituto de Salud Carlos III, 28029 Madrid, Spain.
J Pers Med. 2020 Nov 11;10(4):219. doi: 10.3390/jpm10040219.
Recent studies suggest that long-interspersed nucleotide element-1 () hypomethylation is commonly found in colorectal cancer (CRC), and is associated with worse prognosis. However, the utility of methylation on the prognosis of CRC is still controversial, and may be due to the fact that some clinical and pathological features may affect methylation. Thus, the aim of this study was to assess the prognostic value of tumor methylation in CRC, through their association with the CRC clinical and pathological characteristics. Survival of sixty-seven CRC patients was evaluated according to the median of tumor methylation, as well as pathological and oncological variables. We also studied the association between methylation and pathological features, and finally, we assessed the overall and disease-free survival of methylation, stratified by neoadjuvant treatment and further checked by multivariate Cox regression to assess the statistical interactions. was hypomethylated in the CRC tumor with respect to the tumor adjacent-free area ( < 0.05), without association with any other clinical and oncological features, nor with overall and disease-free survival rates for CRC. Relevantly, in neoadjuvant treatment, methylation was associated with survival rates. Thus, disease-free and overall survival rates of treated CRC patients were worse in the hypomethylated tumors than those with normal methylation ( = 0.004 and 0.0049, respectively). Indeed, was hypermethylated more in the treated patients than in the non-treated patients ( < 0.05). The present study showed that tumor hypomethylation was associated with worse survival rates in only treated patients. Our data suggest an interactive effect of neoadjuvant treatment and tumor methylation, which could be a specific-tissue biomarker to predict survival of the treated patients, and help to personalize treatment in CRC.
近期研究表明，长散在核元件1（LINE-1）低甲基化在结直肠癌（CRC）中普遍存在，且与预后较差相关。然而，LINE-1甲基化对CRC预后的效用仍存在争议，这可能是因为一些临床和病理特征可能会影响LINE-1甲基化。因此，本研究的目的是通过评估肿瘤LINE-1甲基化与CRC临床和病理特征的关联，来评估其在CRC中的预后价值。根据肿瘤LINE-1甲基化的中位数以及病理和肿瘤学变量，评估了67例CRC患者的生存率。我们还研究了LINE-1甲基化与病理特征之间的关联，最后，我们评估了LINE-1甲基化的总生存期和无病生存期，按新辅助治疗进行分层，并通过多变量Cox回归进一步检查以评估统计相互作用。与肿瘤旁无肿瘤区域相比，CRC肿瘤中的LINE-1呈低甲基化（P<0.05），与任何其他临床和肿瘤学特征均无关联，也与CRC的总生存期和无病生存率无关。相关的是，在新辅助治疗中，LINE-1甲基化与生存率相关。因此，LINE-1低甲基化肿瘤的CRC患者的无病生存期和总生存率低于LINE-1甲基化正常的患者（分别为P = 0.004和0.0049）。实际上，接受治疗的患者中LINE-1的高甲基化程度高于未接受治疗的患者（P<0.05）。本研究表明，仅在接受治疗的患者中，肿瘤LINE-1低甲基化与较差的生存率相关。我们的数据表明新辅助治疗与肿瘤LINE-1甲基化之间存在交互作用，这可能是预测接受治疗患者生存率的特异性组织生物标志物，并有助于CRC治疗的个性化。
