Faraj Tabrizi Pouriya, Schimansky Inga, Peters Inga, Hennenlotter Jörg, Tezval Hossein, Kuczyk Markus Antonius, Serth Jürgen
Department of Urology and Urological Oncology, Hannover Medical School, 30625 Hannover, Germany.
Department of Hematology, Hemostaseology, Oncology and Stem Cell Transplantation, Hannover Medical School, 30625 Hannover, Germany.
Cancers (Basel). 2025 Jun 30;17(13):2204. doi: 10.3390/cancers17132204.
Alterations in long non-protein-coding RNAs (lncRNAs) are known to influence cellular proliferation, apoptosis, and metastasis in human cancers, including renal cell carcinoma (RCC). Using pyrosequencing, we analyzed DNA methylation (DNAm) at 23 loci within the CpG island across 28 human cancer cell line models, 181 RCC tumor tissues, 154 paired tumor-adjacent normal tissues (adNs), and 194 metastatic tissue samples. Our analysis revealed that all CpG sites exhibited tumor-specific hypermethylation (all ≤ 1.4 × 10). Moreover, primary RCC tissues with distant metastases (M1) and metastatic tissue samples (Mtx) showed significant hypermethylation compared to RCC without distant metastases (M0). Notably, DNAm in Mtx displayed a significant increase in 22 CpG sites, compared to 12 CpG sites in the M1/M0 comparison, suggesting that DNAm in Mtx differs both qualitatively and quantitatively. Given that elevated levels of DNAm were also observed in the majority of cell line models, our findings suggest that may play a pivotal role in the malignant development and progression of RCC metastasis, as well as in other human cancers.
已知长链非蛋白质编码RNA（lncRNA）的改变会影响包括肾细胞癌（RCC）在内的人类癌症中的细胞增殖、凋亡和转移。我们使用焦磷酸测序法分析了28种人类癌细胞系模型、181个RCC肿瘤组织、154对肿瘤邻近正常组织（adN）和194个转移组织样本中CpG岛内23个位点的DNA甲基化（DNAm）情况。我们的分析显示，所有CpG位点均表现出肿瘤特异性高甲基化（均≤1.4×10）。此外，与无远处转移的RCC（M0）相比，有远处转移的原发性RCC组织（M1）和转移组织样本（Mtx）显示出显著的高甲基化。值得注意的是，与M1/M0比较中的12个CpG位点相比，Mtx中的DNAm在22个CpG位点上显著增加，这表明Mtx中的DNAm在质量和数量上均有所不同。鉴于在大多数细胞系模型中也观察到DNAm水平升高，我们的研究结果表明，其可能在RCC转移以及其他人类癌症的恶性发展和进展中起关键作用。
