骨肉瘤干细胞生物标志物CD117和Stro-1的表达及其临床意义

目的探讨骨肉瘤干细胞生物标志物CD117和Stro-1在骨肉瘤组织中的表达及其与骨肉瘤临床病理因素、患者无瘤生存期的关系。方法采用回顾性研究方法。纳入2014年8月—2017年11月上海交通大学附属第六人民医院手术切除并经病理学检查确诊的58例患者的骨肉瘤切除标本为骨肉瘤组,其中男36例、女22例,年龄10~67(23.16±13.47)岁;另取其中13例患者的瘤旁骨组织标本作为骨组织组。取两组组织蜡块构建组织芯片,采用免疫组织化学法检测组织芯片中骨肉瘤干细胞生物标记物CD117和Stro-1蛋白在骨肉瘤组、骨组织组中的表达情况。在骨肉瘤组织中,分析CD117和Stro-1蛋白表达的相关性;CD117、Stro-1蛋白表达及CD117/Stro-1蛋白双阳性表达与骨肉瘤患者临床病理因素、患者无瘤生存期的关系。结果CD117和Stro-1在骨肉瘤组的阳性表达率分别为51.72%(30/58)和48.28%(28/58),在骨组织组的阳性表达率均为6/13,差异均无统计学意义(P值均>0.05)。在骨肉瘤组中,CD117蛋白与Stro-1蛋白的表达呈正相关(rn=0.864,P<0.01)。CD117蛋白阳性、Stro-1蛋白阳性及CD117/Stro-1蛋白双阳性表达在Enneking外科分期差异均有统计学意义(χ2=6.501、7.374、6.130,P值均<0.05),而与不同年龄、性别间差异均无统计学意义(P值均>0.05)。CD117蛋白阳性30例患者的无瘤生存期中位数为360.00 d,少于阴性28例患者的1260.00 d;Stro-1蛋白阳性28例患者无瘤生存期中位数为330.00 d,少于阴性30例患者的900.00 d;CD117、Stro-1蛋白双阳性27例患者无瘤生存期中位数为360.00 d,少于非双阳性31例患者的900.00 d:差异均有统计学意义(χ2=5.770、4.638、5.391,P值均<0.05)。结论在骨肉瘤组织中,CD117和Stro-1的阳性表达呈正相关,无论哪种蛋白阳性表达,患者临床分期更高,无瘤生存期更短。CD117和Stro-1有望成为预测骨肉瘤患者术后预后情况的重要指标。

Expression and clinical significance of CD117 and Stro-1 in osteosarcoma stem cell surface biomarkers

Objective To investigate the protein expression of osteosarcoma stem cell surface biomarkers, CD117 and Stro-1, and their relationship with the clinicopathologic characteristics as well as disease-free survival (DFS).Methods A retrospective study was adopted. Fifty-eight patients with osteosarcoma who were surgically removed and confirmed by pathological examination in Shanghai Jiao Tong University Affiliated Sixth People's Hospital from August 2014 to November 2017 were selected as the observation group, and 13 cases of adjacent bone tissue were used as the control group. Among them, 36 were male and 22 were female. Age 10-67 (23.16 ± 13.47) years. All tissue were collected to construct tissue microarrays. Immunohistochemistry was used to detect the expression of osteosarcoma stem cell biomarkers CD117 and Stro-1 in the observation group and control group. The correlation between CD117 and Stro-1 protein expression in osteosarcoma tissues was observed. The relationship between the expression of CD117, Stro-1 as well as the double positive expression of CD117/Stro-1 protein and the clinicopathological factors and DFS of patients with osteosarcoma was assessed.Result In observation group, the positive expression rates of CD117 and Stro-1 were 51.72% (30/58) and 48.28% (28/58) respectively. In control group, the positive expression rates were both 6/13, of which the differences showed no significance (all P values＞0.05). In observation group,the positive expression of CD117 protein was positively correlated with that of Stro-1 protein (r_n=0.864, P＜0.01). The differences in the expression of CD117, Stro-1 and the dual positive expression of CD117/Stro-1 were significant in Enneking surgical staging (χ²=6.501, 7.374, 6.130, all P values＜0.05), but not in the age and gender of patients (all P values＞0.05). Median DFS of 30 patients with positive expression of CD117 was 360.00 days, which was less than that of 30 patients with negative expression,1 260.00 days. Median DFS of 28 patients with positive expression of Stro-1 was 330.00 days, which was less than that of 30 patients with negative expression, 900.00 days. Median DFS of 27 patients with dual positive CD117 and Stro-1 protein was 360.00 days, which was less than that of 31 patients without dual positive expression, 900.00 days. The differences were statistically significant (χ² = 5.770, 4.638, 5.391, all P values＜0.05).Conclusions The positive expressions of osteosarcoma stem cell biomarkers CD117 and Stro-1 in osteosarcoma tissues are positively correlated. No matter which protein is positive, patients have higher clinical stage and the shorter tumor-free survival time. CD117 and Stro-1are expected to be an important index to predict the postoperative prognosis of patients with osteosarcoma.