Yamamura Kensuke, Kosumi Keisuke, Baba Yoshifumi, Harada Kazuto, Gao Feng, Zhang Xiaobo, Zhou Lei, Kitano Yuki, Arima Kota, Kaida Takayoshi, Takeyama Hideaki, Higashi Takaaki, Imai Katsunori, Hashimoto Daisuke, Chikamoto Akira, Tan Xiaodong, Baba Hideo
Department of Gastroenterological Surgery, Graduate School of Medical Science, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan.
Department of Pancreatic and Thyroidal Surgery, China Medical University Shengjing Hospital, Shenyang, 110004, People's Republic of China.
Surg Today. 2017 Dec;47(12):1450-1459. doi: 10.1007/s00595-017-1539-1. Epub 2017 May 23.
Global DNA hypomethylation plays an important role in genomic instability and carcinogenesis. The long interspersed nucleotide element-1 (LINE-1) methylation level is a good surrogate marker of the global DNA methylation level. Previously, we demonstrated a strong relationship between LINE-1 hypomethylation and poor prognosis in certain cancers. However, the relationship between the LINE-1 methylation level and the clinical outcome of pancreatic cancer (PC) remains unclear.
We used a pyrosequencing assay to measure LINE-1 methylation levels in 126 samples of resected PC and evaluated the prognostic value of the LINE-1 methylation level.
LINE-1 methylation levels were significantly lower in PC tissues than in matched noncancerous pancreatic tissues (p = 0.039, n = 36). The tumoral LINE-1 methylation range was 41.3-92.8 (n = 126, mean 77.7, median 78.5, standard deviation 5.7). The LINE-1 methylation level was unrelated to clinical and pathological features. Moreover, LINE-1 hypomethylation was not significantly associated with overall survival, cancer specific survival, or disease-free survival (log-rank p = 0.30, p = 0.18 and p = 0.50, respectively).
The LINE-1 methylation level appears not to be associated with poor prognosis in PC. The effect of the LINE-1 methylation level on the survival of PC patients needs to be confirmed in a larger-cohort study.
全基因组DNA低甲基化在基因组不稳定和致癌过程中起重要作用。长散在核元件1(LINE-1)甲基化水平是全基因组DNA甲基化水平的良好替代标志物。此前,我们已证明LINE-1低甲基化与某些癌症的不良预后之间存在密切关系。然而,LINE-1甲基化水平与胰腺癌(PC)临床结局之间的关系仍不清楚。
我们采用焦磷酸测序法检测126例手术切除的PC样本中LINE-1的甲基化水平,并评估LINE-1甲基化水平的预后价值。
PC组织中LINE-1甲基化水平显著低于配对的非癌胰腺组织(p = 0.039,n = 36)。肿瘤组织中LINE-1甲基化范围为41.3 - 92.8(n = 126,均值77.7,中位数78.5,标准差5.7)。LINE-1甲基化水平与临床和病理特征无关。此外,LINE-1低甲基化与总生存期、癌症特异性生存期或无病生存期均无显著相关性(对数秩检验p分别为0.30、0.18和0.50)。
LINE-1甲基化水平似乎与PC的不良预后无关。LINE-1甲基化水平对PC患者生存的影响需要在更大规模的队列研究中得到证实。