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成纤维细胞激活蛋白-α在根治性切除术后非小细胞肺癌中的临床意义:一种新的预后预测因子。

Clinical implications of fibroblast activation protein-α in non-small cell lung cancer after curative resection: a new predictor for prognosis.

机构信息

Department of Thoracic Surgery, Provincial Hospital Affiliated to Shandong University, Shandong University, 324 Jingwu Road, Jinan, 250021, People's Republic of China.

出版信息

J Cancer Res Clin Oncol. 2013 Sep;139(9):1523-8. doi: 10.1007/s00432-013-1471-8. Epub 2013 Jul 9.

Abstract

BACKGROUND

Fibroblast activation protein-α (FAP-α), which is a serine protease specially expressed on the surface of the cancer stromal cells, plays an important role in the progression and prognosis in diverse malignancies. However, the role of FAP-α in non-small cell lung cancer (NSCLC) is still unknown.

MATERIALS AND METHODS

We enrolled 59 NSCLC patients who received complete resection. Sections of paraffin-embedded primary NSCLC specimens of all the patients were stained with antibody directed against FAP-α. Overall, percentage (Grade 0-3) and intensity (0-3+) of stromal FAP-α staining of the tumor were assessed.

RESULTS

FAP-α was detected in >76 % of the specimens examined, and its high expression seemed to be correlated with poor tumor differentiation (P = 0.06). Furthermore, both increased FAP-α staining percentage and intensity were associated with worse overall survival of the patients (percentage, P = 0.0087; intensity, P = 0.05). Higher FAP-α staining percentage was observed in those patients with increased peripheral neutrophil and lymphocyte count ratio (P = 0.034).

CONCLUSIONS

FAP-α is highly expressed in cancer stroma and also a predictor of poor survival of NSCLC patients. Elevated FAP-α expression may be associated with inflammation and suppressed lymphocyte-dependent immune response, which then result in the tumor progression. Therefore, FAP-α plays an important role in the progression of NSCLC, and its high expression is a predictor of poor survival. Targeting FAP-α may be a novel strategy for NSCLC therapy.

摘要

背景

成纤维细胞激活蛋白-α(FAP-α)是一种在肿瘤间质细胞表面特异性表达的丝氨酸蛋白酶,在多种恶性肿瘤的进展和预后中发挥重要作用。然而,FAP-α 在非小细胞肺癌(NSCLC)中的作用尚不清楚。

材料和方法

我们纳入了 59 名接受完全切除术的 NSCLC 患者。对所有患者的石蜡包埋原发性 NSCLC 标本进行了针对 FAP-α 的抗体染色。总体上,评估了肿瘤间质 FAP-α 染色的百分比(Grade 0-3)和强度(0-3+)。

结果

在检查的>76%的标本中检测到 FAP-α,其高表达似乎与肿瘤分化不良相关(P=0.06)。此外,FAP-α 染色百分比和强度的增加均与患者的总生存期较差相关(百分比,P=0.0087;强度,P=0.05)。在那些外周中性粒细胞和淋巴细胞计数比值增加的患者中,观察到更高的 FAP-α 染色百分比(P=0.034)。

结论

FAP-α在肿瘤间质中高度表达,也是 NSCLC 患者生存不良的预测因子。FAP-α 表达的增加可能与炎症和抑制淋巴细胞依赖性免疫反应有关,从而导致肿瘤进展。因此,FAP-α 在 NSCLC 的进展中起重要作用,其高表达是生存不良的预测因子。靶向 FAP-α 可能是 NSCLC 治疗的一种新策略。

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