Digestive Disease Center, Guangzhou Panyu Central Hospital, Guangzhou 511400, China.
Translational Medicine Center, Guangdong Women and Children Hospital, Guangzhou 511400, China.
Ann Diagn Pathol. 2022 Oct;60:152021. doi: 10.1016/j.anndiagpath.2022.152021. Epub 2022 Aug 3.
Molecular markers for the detection of lymph node micrometastases of malignant tumors have been extensively investigated. However, epigenetic signatures have rarely been reported for identification of metastatic lymph nodes and disease relapse. Septin 9 is the most frequently reported hypermethylated gene in colorectal cancer (CRC). This study aimed to assess the clinical relevance of Septin 9 methylation in regional lymph nodes in recurrence/metastases of CRC.
We analyzed Septin 9 methylation of DNA from resected lymph nodes in 75 CRC patients with or without tumor recurrence using quantitative methylation-sensitive PCR (qMS-PCR).
Of the 30 histologically negative lymph node CRC patients without recurrence (group 1), methylated Septin 9 was detected in 3 (10 %) cases. The positivity rate of methylated Septin 9 in group 2 containing 30 histologically node-negative CRC patients with recurrence was 30 % (9/30). For group 3, lymphatic invasion as well as tumor recurrence, 11 (73 %) out of 15 subjects had Septin 9 methylation-positive lymph nodes. Moreover, patients in group 3 had a higher level of methylated Septin 9 compared to subjects in group 1 and group 2 (p < 0.05). In addition, CRC patients with Septin 9 methylation in lymph nodes had significantly reduced survival (Log-rank P < 0.0001).
Our data support the predictive role of Septin 9 methylation analysis of lymph node micrometastases for tumor relapse after surgery.
用于检测恶性肿瘤淋巴结微转移的分子标志物已得到广泛研究。然而，很少有报道称表观遗传特征可用于识别转移性淋巴结和疾病复发。Septin 9 是结直肠癌（CRC）中最常报道的高甲基化基因。本研究旨在评估 Septin 9 甲基化在 CRC 局部淋巴结复发/转移中的临床相关性。
我们使用定量甲基敏感 PCR（qMS-PCR）分析了 75 例 CRC 患者手术切除的淋巴结中 DNA 的 Septin 9 甲基化情况，这些患者中有或无肿瘤复发。
在 30 例无组织学淋巴结阳性且无复发的 CRC 患者（组 1）中，有 3 例（10%）检测到甲基化 Septin 9。在包含 30 例组织学淋巴结阴性但有复发的 CRC 患者的组 2 中，甲基化 Septin 9 的阳性率为 30%（9/30）。对于组 3，淋巴管浸润以及肿瘤复发，15 例中有 11 例（73%）存在甲基化 Septin 9 的淋巴结。此外，与组 1 和组 2 相比，组 3 中的患者具有更高水平的甲基化 Septin 9（p<0.05）。此外，淋巴结中存在 Septin 9 甲基化的 CRC 患者的生存时间明显缩短（对数秩 P<0.0001）。
我们的数据支持淋巴结微转移中 Septin 9 甲基化分析对手术后肿瘤复发的预测作用。
