Marwitz Sebastian, Heinbockel Lena, Scheufele Swetlana, Kugler Christian, Reck Martin, Rabe Klaus F, Perner Sven, Goldmann Torsten, Ammerpohl Ole
Pathology of the University Medical Center Schleswig-Holstein (UKSH), Campus Luebeck and the Research Center Borstel, site Borstel, Germany.
Airway Research Center North, Member of the German Center for Lung Research (DZL), Großhansdorf, Germany.
Int J Cancer. 2018 Dec 15;143(12):3061-3070. doi: 10.1002/ijc.31641. Epub 2018 Oct 16.
Aging affects the core processes of almost every organism, and the functional decline at the cellular and tissue levels influences disease development. Recently, it was shown that the methylation of certain CpG dinucleotides correlates with chronological age and that this epigenetic clock can be applied to study aging-related effects. We investigated these molecular age loci in non-small cell lung cancer (NSCLC) tissues from patients with adenocarcinomas (AC) and squamous cell carcinomas (SQC) as well as in matched tumor-free lung tissue. In both NSCLC subtypes, the calculated epigenetic age did not correlate with the chronological age. In particular, SQC exhibited rejuvenation compared to the corresponding normal lung tissue as well as with the chronological age of the donor. Moreover, the younger epigenetic pattern was associated with a trend toward stem cell-like gene expression patterns. These findings show deep phenotypic differences between the tumor entities AC and SQC, which might be useful for novel therapeutic and diagnostic approaches.
衰老影响几乎每个生物体的核心过程，细胞和组织水平的功能衰退会影响疾病发展。最近研究表明，某些CpG二核苷酸的甲基化与实足年龄相关，并且这种表观遗传时钟可用于研究衰老相关效应。我们研究了来自腺癌（AC）和鳞状细胞癌（SQC）患者的非小细胞肺癌（NSCLC）组织以及匹配的无肿瘤肺组织中的这些分子年龄位点。在两种NSCLC亚型中，计算出的表观遗传年龄与实足年龄不相关。特别是，与相应的正常肺组织以及供体的实足年龄相比，SQC表现出年轻化。此外，较年轻的表观遗传模式与干细胞样基因表达模式的趋势相关。这些发现表明肿瘤实体AC和SQC之间存在深刻的表型差异，这可能对新的治疗和诊断方法有用。
