Diviney Andrea, Chobrutskiy Boris I, Zaman Saif, Blanck George
1Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, 12901 Bruce B. Downs Bd. MDC7, Tampa, USA.
2Immunology Program, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612 USA.
Cancer Cell Int. 2019 Mar 27;19:73. doi: 10.1186/s12935-019-0790-5. eCollection 2019.
Pediatric cancer survival rates overall have been improving, but neuroblastoma (NBL) and acute lymphoblastic leukemia (ALL), two of the more prevalent pediatric cancers, remain particularly challenging. One issue not yet fully addressed is distinctions attributable to age of diagnosis.
In this report, we verified a survival difference based on diagnostic age for both pediatric NBL and pediatric ALL datasets, with younger patients surviving longer for both diseases. We identified several gene expression markers that correlated with age, along a continuum, and then used a series of age-independent survival metrics to filter these initial correlations.
For pediatric NBL, we identified 2 genes that are expressed at a higher level in lower surviving patients with an older diagnostic age; and 4 genes that are expressed at a higher level in longer surviving patients with a younger diagnostic age. For pediatric ALL, we identified 3 genes expressed at a higher level in lower surviving patients with an older diagnostic age; and 17 genes expressed at a higher level in longer surviving patients with a younger diagnostic age.
This process implicated pan-chromosome effects for chromosomes 11 and 17 in NBL; and for the X chromosome in ALL.
总体而言，儿童癌症的生存率一直在提高，但神经母细胞瘤（NBL）和急性淋巴细胞白血病（ALL）这两种较为常见的儿童癌症仍然极具挑战性。一个尚未得到充分解决的问题是诊断年龄所导致的差异。
在本报告中，我们验证了儿童NBL和儿童ALL数据集基于诊断年龄的生存差异，两种疾病中年龄较小的患者生存期更长。我们沿着一个连续体确定了几个与年龄相关的基因表达标志物，然后使用一系列与年龄无关的生存指标来筛选这些初始相关性。
对于儿童NBL，我们鉴定出在诊断年龄较大、生存期较短的患者中表达水平较高的2个基因；以及在诊断年龄较小、生存期较长的患者中表达水平较高的4个基因。对于儿童ALL，我们鉴定出在诊断年龄较大、生存期较短的患者中表达水平较高的3个基因；以及在诊断年龄较小、生存期较长的患者中表达水平较高的17个基因。
这一过程表明11号和17号染色体在NBL中存在全染色体效应；而X染色体在ALL中存在全染色体效应。
