He Lile, Shi Xiangyu, Chen Ruiqi, Wu Zhengchun, Yang Zhulin, Li Zhihong
Department of Orthopedics, The Second Xiangya Hospital, Central South University, Changsha, China.
Hunan Key Laboratory of Tumor Models and Individualized Medicine, Changsha, China.
Front Mol Biosci. 2019 Nov 26;6:134. doi: 10.3389/fmolb.2019.00134. eCollection 2019.
Chondrosarcoma is the second most common malignant bone tumor. Current therapies remain ineffective, resulting in poor prognoses. Biomarkers for chondrosarcoma and predictors of its prognosis have not been established. Mental health-related proteins have been associated with the pathogenesis, progression, and prognosis of many cancers, but their association with chondrosarcoma has not been reported. In this study, the expression and clinicopathological significance of the mental health-related proteins DAXX, DRD3, and DISC1 in chondrosarcoma tissue samples were examined, over an 84-months follow-up period. In immunohistochemical analysis, the rates of positive DAXX, DRD3, and DISC1 expression were significantly higher in chondrosarcoma than in osteochondroma tissue ( < 0.01). The percentages of positive DAXX, DRD3, and DISC1 expression were significantly lower in tissues with good differentiation ( < 0.01), AJCC stage I/ II ( < 0.01), Enneking stage I ( < 0.01), and non-metastasis ( < 0.05), respectively. In Kaplan-Meier survival analysis, significantly shorter mean survival times were associated with moderate and poor differentiation ( = 0.000), AJCC stage III/IV ( = 0.000), Enneking stage II/III ( = 0.000), metastasis ( = 0.019), invasion ( = 0.013), and positive DAXX ( = 0.012), and/or DRD3 ( = 0.018) expression. In Cox regression analysis, moderate and poor differentiation ( = 0.006), AJCC stage III/IV ( = 0.013), Enneking stage II/III ( = 0.016), metastasis ( = 0.033), invasion ( = 0.011), and positive DAXX ( = 0.033), and/or DRD3 ( = 0.025) staining correlated negatively with the postoperative survival rate and positively with mortality. In competing-risks regression analysis, differentiation ( = 0.005), metastasis ( = 0.014), invasion ( = 0.028), AJCC stage ( = 0.003), Enneking stage ( = 0.036), and DAXX ( = 0.039), and DRD3( = 0.019) expression were independent predictors of death from chondrosarcoma. The areas under receiver operating characteristic curves for DAXX, DRD3, and DISC1 expression were 0.673 (95% CI, 0.557-0.788; = 0.010), 0.670 (95% CI, 0.556-0.784; = 0.011), and 0.688 (95% CI, 0.573-0.802; = 0.005), respectively. These results suggest that DAXX, DRD3, and DISC1 could serve as biomarkers of chondrosarcoma progression and predictors of its prognosis.
软骨肉瘤是第二常见的恶性骨肿瘤。目前的治疗方法仍然无效,导致预后不良。软骨肉瘤的生物标志物及其预后预测指标尚未确立。与心理健康相关的蛋白质已被证明与许多癌症的发病机制、进展及预后相关,但它们与软骨肉瘤的关系尚未见报道。在本研究中,我们对软骨肉瘤组织样本进行了长达84个月的随访,检测了与心理健康相关的蛋白质DAXX、DRD3和DISC1的表达及其临床病理意义。免疫组化分析显示,软骨肉瘤组织中DAXX、DRD3和DISC1的阳性表达率显著高于骨软骨瘤组织(P<0.01)。在高分化组织(P<0.01)、AJCC分期I/II期(P<0.01)、Enneking分期I期(P<0.01)及无转移组织(P<0.05)中,DAXX、DRD3和DISC1的阳性表达率显著降低。Kaplan-Meier生存分析显示,中低分化(P = 0.000)、AJCC分期III/IV期(P = 0.000)、Enneking分期II/III期(P = 0.000)、转移(P = 0.019)、侵袭(P = 0.013)以及DAXX阳性(P = 0.012)和/或DRD3阳性(P = 0.018)表达与平均生存时间显著缩短相关。Cox回归分析显示,中低分化(P = 0.006)、AJCC分期III/IV期(P = 0.013)、Enneking分期II/III期(P = 0.016)、转移(P = 0.033)、侵袭(P = 0.011)以及DAXX阳性(P = 0.033)和/或DRD3阳性(P = 0.025)染色与术后生存率呈负相关,与死亡率呈正相关。竞争风险回归分析显示,分化程度(P = 0.005)、转移(P = 0.014)、侵袭(P = 0.028)、AJCC分期(P = 0.003)、Enneking分期(P = 0.036)以及DAXX(P = 0.039)和DRD3(P = 0.019)表达是软骨肉瘤死亡的独立预测因素。DAXX、DRD3和DISC1表达的受试者工作特征曲线下面积分别为0.673(95%CI,0.557 - 0.788;P = 0.010)、0.670(95%CI,0.556 - 0.784;P = 0.011)和0.688(95%CI,0.573 - 0.802;P = 0.005)。这些结果表明,DAXX、DRD3和DISC1可作为软骨肉瘤进展的生物标志物及其预后的预测指标。