Liang Shoulei, Ren Zhiwu, Han Xiuxin, Yang Jilong, Shan Luling, Li Lin, Wang Binying, Zhang Qianyi, Mu Tianyang, Chen Kexin, Xiong Shunbin, Wang Guowen
Department of Bone and Soft Tissue Tumors, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China.
Institute of Cancer Stem Cell, Dalian Medical University Cancer Center, Dalian, China.
PLoS One. 2015 May 18;10(5):e0127236. doi: 10.1371/journal.pone.0127236. eCollection 2015.
Osteosarcoma is the most frequent type of malignant bone tumor in children and adolescents and is associated with a high propensity for lung metastasis. Recent experiments have indicated that PLA2G16 contributes to osteosarcoma progression and metastasis in both mouse and human osteosarcoma cell lines. The aim of this study was to compare the expression of PLA2G16 in non-metastatic and metastatic osteosarcomas to determine whether PLA2G16 expression can serve as a biomarker of osteosarcoma prognosis and metastasis.
Quantitative real-time PCR was used to examine PLA2G16 mRNA in primary osteosarcoma patients (18 patients without metastases and 17 patients with metastases), and immunohistochemistry (IHC) staining of PLA2G16 was performed on tissue microarrays from 119 osteosarcoma patients. Tumor metastatic behavior and survival of the patients were followed up for a minimum of 36 months and a maximum of 171 months. The prognostic value of PLA2G16 expression was evaluated by the Kaplan-Meier method and a log-rank test. Multivariate Cox regression analysis was used to identify significant independent prognostic factors.
Osteosarcoma patients with metastasis showed a higher expression of PLA2G16 at both the mRNA and protein levels (both at P values< 0.05) than did patients without metastasis. Osteosarcoma patients with positive IHC staining of PLA2G16 expression at primary sites had shorter overall survival and metastasis-free survival (both at P values <0.02). Moreover, multivariate Cox analysis identified PLA2G16 expression as an independent prognostic factor to predict poor overall survival and metastasis-free survival (both P values < 0.03).
This study indicated that PLA2G16 expression is a significant prognostic factor in primary osteosarcoma patients for predicting the development of metastases and poor survival.
骨肉瘤是儿童和青少年中最常见的恶性骨肿瘤类型，且具有较高的肺转移倾向。最近的实验表明，磷脂酶A2G16（PLA2G16）在小鼠和人类骨肉瘤细胞系中均促进骨肉瘤的进展和转移。本研究的目的是比较PLA2G16在非转移性和转移性骨肉瘤中的表达，以确定PLA2G16表达是否可作为骨肉瘤预后和转移的生物标志物。
采用定量实时PCR检测原发性骨肉瘤患者（18例无转移患者和17例有转移患者）的PLA2G16 mRNA，并对119例骨肉瘤患者的组织芯片进行PLA2G16免疫组化（IHC）染色。对患者的肿瘤转移行为和生存情况进行了至少36个月、最长171个月的随访。采用Kaplan-Meier法和对数秩检验评估PLA2G16表达的预后价值。采用多因素Cox回归分析确定显著的独立预后因素。
与无转移的患者相比，有转移的骨肉瘤患者在mRNA和蛋白水平上PLA2G16的表达均较高（P值均<0.05）。原发性部位PLA2G16表达免疫组化染色阳性的骨肉瘤患者总生存期和无转移生存期均较短（P值均<0.02）。此外，多因素Cox分析确定PLA2G16表达是预测总生存期差和无转移生存期差的独立预后因素（P值均<0.03）。
本研究表明，PLA2G16表达是原发性骨肉瘤患者预测转移发生和生存不良的重要预后因素。
