Contreras-Romero Carlos, Pérez-Yépez Eloy-Andrés, Martinez-Gutierrez Antonio Daniel, Campos-Parra Alma, Zentella-Dehesa Alejandro, Jacobo-Herrera Nadia, López-Camarillo César, Corredor-Alonso Guillermo, Martínez-Coronel Jaime, Rodríguez-Dorantes Mauricio, de León David Cantu, Pérez-Plasencia Carlos
Laboratorio de Genómica, Insituto Nacional de Cancerología, Ciudad de México, Mexico.
Cátedra CONACYT, Dirección de cátedras, Consejo Nacional de Ciencia y Tecnología (CONACYT), Mexico City, Mexico.
Front Oncol. 2022 Mar 3;12:773438. doi: 10.3389/fonc.2022.773438. eCollection 2022.
Despite efforts to promote health policies focused on screening and early detection, cervical cancer continues to be one of the leading causes of mortality in women; in 2020, estimated 30,000 deaths in Latin America were reported for this type of tumor. While the therapies used to treat cervical cancer have excellent results in tumors identified in early stages, those women who are diagnosed in locally advanced and advanced stages show survival rates at 5 years of <50%. Molecular patterns associated with clinical response have been studied in patients who present resistance to treatment; none of them have reached clinical practice. It is therefore necessary to continue analyzing molecular patterns that allow us to identify patients at risk of developing resistance to conventional therapy. In this study, we analyzed the global methylation profile of 22 patients diagnosed with locally advanced cervical cancer and validated the genomic results in an independent cohort of 70 patients. We showed that BRD9 promoter region methylation and CTU1 demethylation were associated with a higher overall survival (p = 0.06) and progression-free survival (p = 0.0001), whereas DOCK8 demethylation was associated with therapy-resistant patients and a lower overall survival and progression-free survival (p = 0.025 and p = 0.0001, respectively). Our results suggest that methylation of promoter regions in specific genes may provide molecular markers associated with response to treatment in cancer; further investigation is needed.
尽管人们努力推行以筛查和早期检测为重点的卫生政策，但宫颈癌仍是女性死亡的主要原因之一；2020年，拉丁美洲估计有3万例此类肿瘤导致的死亡报告。虽然用于治疗宫颈癌的疗法在早期发现的肿瘤中效果极佳，但那些被诊断为局部晚期和晚期的女性，其5年生存率<50%。对于出现治疗耐药性的患者，已对与临床反应相关的分子模式进行了研究；但这些研究均未应用于临床实践。因此，有必要继续分析分子模式，以便我们识别出有对传统疗法产生耐药性风险的患者。在本研究中，我们分析了22例被诊断为局部晚期宫颈癌患者的全基因组甲基化谱，并在一个由70名患者组成的独立队列中验证了基因组结果。我们发现，BRD9启动子区域甲基化和CTU1去甲基化与较高的总生存率（p = 0.06）和无进展生存率（p = 0.0001）相关，而DOCK8去甲基化与治疗耐药患者以及较低的总生存率和无进展生存率相关（分别为p = 0.025和p = 0.0001）。我们的结果表明，特定基因启动子区域的甲基化可能提供与癌症治疗反应相关的分子标志物；还需要进一步研究。
