Background

The 16q23.1 tumor suppressor gene (TSG) of ADAMTS18 has been identified to be aberrant methylated in clear cell renal cell carcinoma (ccRCC), and there still exists an unclear situation between its methylation and the progression of ccRCC.

Objective

To analyze the biological function and mechanism of ADAMTS18 gene in the tumorigenesis and progression of ccRCC.

Methods

We examined ADAMTS18 gene methylation using methylation- specific polymerase chain reaction (MSP) in 92 ccRCC primary tumors from September 2017 to May 2018. Using reverse transcriptase PCR (RT-PCR) and immunohistochemical (IHC) assay, the relative expression level of ADAMTS18 was measured in the representative tumor samples with their adjacent normal tissues. Meanwhile, colony formation, cell viability, wound healing, transwell chamber, flow cytometry, and PI staining were performed to confirm the tumor-suppressive function and mechanism of ADAMTS18 gene.

Results

Aberrant methylation was further detected in 47 of the 92 (51.1%) primary tumors and in 8 of the 92 (8.7%) adjacent normal tissues (p < 0.05). Due to the phenomenon of aberrant methylation, ectopic low-level expression of ADAMTS18 gene could result in the promotion of tumorigenesis and progression in ccRCC.

Conclusion

The aberrantly methylated ADAMTS18 gene may be involved in the tumorigenesis and progression of ccRCC.

中文翻译：

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16q23.1 肿瘤抑制基因 ADAMTS18 的异常甲基化促进透明细胞肾细胞癌的发生和进展

背景

ADAMTS18的16q23.1肿瘤抑制基因（TSG）已被鉴定在透明细胞肾细胞癌（ccRCC）中发生异常甲基化，其甲基化与ccRCC的进展之间仍存在不清楚的情况。

客观的

分析ADAMTS18基因在ccRCC肿瘤发生发展中的生物学功能及机制。

方法

我们使用甲基化特异性聚合酶链反应 (MSP) 检测了 2017 年 9 月至 2018 年 5 月 92 例 ccRCC 原发性肿瘤中的 ADAMTS18 基因甲基化。使用逆转录酶 PCR (RT-PCR) 和免疫组织化学 (IHC) 测定，ADAMTS18 的相对表达水平为在代表性肿瘤样本及其邻近的正常组织中测量。同时，通过集落形成、细胞活力、伤口愈合、Transwell小室、流式细胞术和PI染色来确认ADAMTS18基因的抑癌功能和机制。

结果

在 92 个 (51.1%) 原发性肿瘤中的 47 个和 92 个 (8.7%) 相邻正常组织中的 8 个中进一步检测到异常甲基化 ( p  < 0.05)。由于异常甲基化现象，ADAMTS18基因的异位低水平表达可能导致ccRCC的肿瘤发生和进展。

结论

异常甲基化的 ADAMTS18 基因可能参与 ccRCC 的肿瘤发生和进展。