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血清碱性磷酸酶升高与 MMP-9 联合预测中国南方地区原发性骨肉瘤患者的转移和预后不良。

High serum alkaline phosphatase cooperating with MMP-9 predicts metastasis and poor prognosis in patients with primary osteosarcoma in Southern China.

机构信息

1st Affiliated Hospital of Sun Yat-sen University, Pathological Department, Guangzhou, P R China.

出版信息

World J Surg Oncol. 2012 Feb 15;10:37. doi: 10.1186/1477-7819-10-37.

DOI:10.1186/1477-7819-10-37
PMID:22333159
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3305572/
Abstract

BACKGROUND

Osteosarcoma is a malignant tumor with high ability to form invasion and metastasis. Identifying prognostic factor in osteosarcoma is helpful to select those patients for more aggressive management. Our study evaluated serum alkaline phosphatase (ALP) cooperating with matrix metalloproteinase-9 (MMP-9) as an important prognostic predictor for local recurrence and distant metastasis of osteosarcoma.

METHODS

177 cases were included from the osteosarcoma patients treated at 1st Affiliated Hospital of Sun Yat-sen University (1999-2008). Pre-chemotherapy serum ALP (pre-ALP) were studied and correlated with tumor recurrence, lung metastasis and patient survival. MMP-9 protein in tumor tissues was detected by immunohistochemistry and correlated with pre-ALP level.

RESULTS

Pre-ALP were partitioned into normal, high, and very high groups, in each group the incidence of metastases was 12.2%, 21.2% and 34.6%, respectively (p = 0.007). In the three groups the mean disease-free survival (DFS) was 57 ± 3.15, 28 ± 3.57 and 14 ± 3.35 months, respectively (p < 0.001); overall survival (OS) was 92 ± 26.89, 39 ± 8.61 and 17 ± 5.07 months, respectively (p < 0.001). By multivariate analysis, elevated serum pre-ALP were associated with shorter DFS (p = 0.018) and OS (p = 0.031). If elevated ALP levels decreased after clinical treatment, the incidence of lung metastasis rate decreased (p = 0.028); DFS and OS were both prolonged (p < 0.001). Pre-ALP was also positively correlated with MMP-9 expression (p = 0.015) in tumor tissue.

CONCLUSIONS

Pre-ALP was an independent prognostic factor for the survival of osteosarcoma patients in south China, and correlated with MMP-9 expression and lung metastasis. ALP can also serve as a prognostic marker for treatment, and merit large-scale validation studies.

摘要

背景

骨肉瘤是一种恶性肿瘤,具有高度侵袭和转移的能力。识别骨肉瘤的预后因素有助于选择那些需要更积极治疗的患者。我们的研究评估了血清碱性磷酸酶(ALP)与基质金属蛋白酶-9(MMP-9)联合作为骨肉瘤局部复发和远处转移的重要预后预测指标。

方法

从中山大学第一附属医院(1999-2008 年)治疗的骨肉瘤患者中纳入 177 例。研究了化疗前血清 ALP(pre-ALP),并将其与肿瘤复发、肺转移和患者生存相关联。用免疫组织化学法检测肿瘤组织中 MMP-9 蛋白,并与 pre-ALP 水平相关联。

结果

pre-ALP 分为正常、高和极高三组,每组转移发生率分别为 12.2%、21.2%和 34.6%(p = 0.007)。在三组中,无病生存(DFS)的平均时间分别为 57 ± 3.15、28 ± 3.57 和 14 ± 3.35 个月,(p < 0.001);总生存(OS)分别为 92 ± 26.89、39 ± 8.61 和 17 ± 5.07 个月,(p < 0.001)。多因素分析显示,血清 pre-ALP 升高与 DFS (p = 0.018)和 OS (p = 0.031)较短有关。如果升高的 ALP 水平在临床治疗后降低,肺转移率降低(p = 0.028);DFS 和 OS 均延长(p < 0.001)。pre-ALP 也与肿瘤组织中 MMP-9 表达呈正相关(p = 0.015)。

结论

pre-ALP 是华南地区骨肉瘤患者生存的独立预后因素,与 MMP-9 表达和肺转移相关。ALP 也可以作为治疗的预后标志物,值得进行大规模验证研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/efd6/3305572/d93c713eae1d/1477-7819-10-37-4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/efd6/3305572/37b4ab86f4bf/1477-7819-10-37-1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/efd6/3305572/57b6e7db5f10/1477-7819-10-37-2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/efd6/3305572/b20f377663cb/1477-7819-10-37-3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/efd6/3305572/d93c713eae1d/1477-7819-10-37-4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/efd6/3305572/37b4ab86f4bf/1477-7819-10-37-1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/efd6/3305572/57b6e7db5f10/1477-7819-10-37-2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/efd6/3305572/b20f377663cb/1477-7819-10-37-3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/efd6/3305572/d93c713eae1d/1477-7819-10-37-4.jpg

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