Epigenetic down-regulation of SOX2 is an independent poor prognostic factor for hypopharyngeal cancers
Epigenetic down-regulation of SOX2 is an independent poor prognostic factor for hypopharyngeal cancers
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DOI：
10.1111/his.13436
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发表时间：
2018-04-01
期刊：
影响因子：
6.4
通讯作者：
Zen, Yoh
中科院分区：
文献类型：
--
作者：
Avincsal, Mehmet Ozgur;Jimbo, Naoe;Zen, Yoh
目的我们最近报道了一小部分(7%)完全缺乏SOX2表达的食管鳞癌具有独特的临床病理特征和糟糕的预后。本研究的目的是阐明食道癌的研究结果是否适用于下咽鳞状细胞癌(HPSCCs)或口咽鳞状细胞癌(OPSCCs)。方法与结果：本研究队列包括130例HPSCC和65例OPSCC患者。免疫组织化学染色显示，130例HPSCC中10例(8%)SOX2几乎完全阴性，65例OPSCC中7例(11%)SOX2表达阴性。SOX2阳性癌和SOX2阴性癌在包括p16状态在内的临床病理特征上无显著差异。然而，SOX2阴性的HPSCC患者的总体和无复发生存率显著低于SOX2阳性的HPSCC患者，而这种预后关系在OPSCC患者中尚未得到证实。在多变量分析中，SOX2表达缺失似乎是HPSCC患者预后不良的独立因素。在测序分析中，未发现SOX2基因突变。由于已知SOX2在转录起始点之前含有一个广泛的CpG岛，因此对SOX2启动子进行了甲基化特异性聚合酶链式反应。在10例SOX2阴性的HPSCC中有9例发现甲基化等位基因，而在SOX2阳性的HPSCC中没有发现甲基化等位基因。结论与食道癌相似，一小部分几乎完全缺乏SOX2表达的HPSCC(8%)似乎是具有高复发率的侵袭性肿瘤。启动子高甲基化被确定为表观遗传SOX2沉默的主要机制。
AimsWe recently reported that a small subset (7%) of oesophageal squamous cell carcinomas completely lacking SOX2 expression had unique clinicopathological features and a dismal prognosis. The aim of the present study was to elucidate whether the findings obtained in oesophageal cancers are applicable to hypopharyngeal squamous cell carcinomas (HPSCCs) or oropharyngeal squamous cell carcinomas (OPSCCs).Methods and resultsThe study cohort consisted of consecutive patients with HPSCC (n=130) and OPSCC (n=65) who underwent surgery without preoperative therapy. On immunostaining, SOX2 was almost entirely negative in 10 of 130 HPSCCs (8%) and seven of 65 OPSCCs (11%). No significant differences were observed in clinicopathological features, including p16 status, between SOX2-positive and SOX2-negative cancers. However, patients with SOX2-negative HPSCC had significantly worse overall and recurrence-free survival than those with SOX2-positive HPSCC, whereas such a prognostic relationship was not confirmed in patients with OPSCC. In a multivariate analysis, the loss of SOX2 expression appeared to be an independent poor prognostic factor for patients with HPSCC. In a sequencing analysis, no mutation was found in SOX2. As SOX2 is known to contain an extensive CpG island before the transcription start site, methylation-specific polymerase chain reaction for the SOX2 promoter was performed. Methylated alleles were found in nine of 10 SOX2-negative HPSCCs but in none of SOX2-positive HPSCCs.ConclusionsSimilarly to oesophageal cancers, a small subset (8%) of HPSCCs characteristically almost completely lacking SOX2 expression appeared to be aggressive neoplasms with high recurrence rates. Promoter hypermethylation was determined to be a major mechanism underlying epigenetic SOX2 silencing.