目的:新的证据表明骨肉瘤干细胞(OSCs)可能是肿瘤起始传播的原因,复发,和对治疗的抵抗力。我们着手评估活检和切除样本中ALDH1A1和CD44阳性细胞的丰度与疾病复发和总生存期之间的关系。
方法:对20例患者进行回顾性分析,包括活检和切除样本,在综合癌症中心进行。此外,我们查询了公开的骨肉瘤患者TARGET数据集.
结果:在活检或切除样本中,ALDH1A1阳性细胞和CD44阳性细胞的百分比与总死亡率或疾病复发均无显著相关。与我们的机构数据不同,在单变量分析和年龄校正分析中,TARGET数据集中的总生存期与较高的ALDH1A1表达显著相关.
结论:ADLH1和CD44,OSCs的潜在标志物,没有发现是骨肉瘤患者生存的可靠的临床免疫组织化学预后标志物,特别是无病生存。高ALDH1A1RNA表达的骨肉瘤患者在检查骨肉瘤患者的国家基因组数据库中显示出改善的总体生存率,但与无病生存率无关。CD44和ALDH1A1作为生存的细胞特异性预后标志物的潜力,和尽可能的分子靶标,可能仅限于骨肉瘤。
OBJECTIVE: Emerging evidence suggests that osteosarcoma stem cells (OSCs) may be responsible for tumor initiation propagation, recurrence, and resistance to therapy. We set out to evaluate the relationship between the abundance of ALDH1A1 and CD44-positive cells in biopsy and resection samples on disease recurrence and overall survival.
METHODS: A retrospective review of 20 patients, including biopsy and resection samples, was performed at a comprehensive cancer center. Additionally, we queried the publicly available TARGET dataset of osteosarcoma patients.
RESULTS: Neither the percentages of ALDH1A1-positive cells nor CD44-positive cells were significantly associated with overall mortality or disease recurrence in either biopsy or resection samples. Unlike our institutional data, overall survival was significantly correlated to higher ALDH1A1 expression in the TARGET dataset both in univariate and age-adjusted analyses.
CONCLUSIONS: ADLH1 and CD44, potential markers of OSCs, were not found to be reliable clinical immunohistochemical prognostic markers for osteosarcoma patient survival, specifically disease-free survival. Osteosarcoma patients with high ALDH1A1 RNA expression showed improved overall survival in examining a national genomic database of osteosarcoma patients but again no association with disease-free survival. The potential of CD44 and ALDH1A1 as cellular-specific prognostic markers of survival, and as possible molecular targets, may be limited in osteosarcoma.