Septin 9 methylation analysis of lymph node micrometastases for predicting relapse of colorectal cancer

• Published in: Annals of diagnostic pathology Vol. 60; p. 152021
• Main Authors: Wan, Yu, Liang, Jun-Jie, Luo, Xi-Jun, Zhu, Xian-Jun, He, Jia-Lin, Wang, Sheng-Bo, Zhao, Ying-Ying, Zeng, Di, Zhang, Liang, Tang, Xing-Kui
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 01.10.2022
• Subjects: Colorectal cancer; Lymph node micrometastasis; Methylation marker; Septin 9; Survival; Tumor recurrence; Methylation marker; Lymph node micrometastasis; Tumor recurrence; Septin 9; Survival; Colorectal cancer
• ISSN: 1092-9134; 1532-8198
• DOI: 10.1016/j.anndiagpath.2022.152021

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. •Positivity rates of Septin 9 methylation in lymph nodes linked to CRC phenotypes.•CRC patients with higher levels of Septin 9 methylation had reduced survival.•Septin 9 methylation analysis of lymph nodes can predict CRC progression.