Massy E, Rousseau J C, Gueye M, Bonnelye E, Brevet M, Chambard L, Duruisseaux M, Borel O, Roger C, Guelminger R, Pialat J B, Gineyts E, Bouazza L, Millet M, Maury J M, Clézardin P, Girard N, Confavreux Cyrille B
INSERM UMR 1033-LYOS, Lyon, France.
Université de Lyon, France.
J Bone Oncol. 2021 Jun 5;29:100364. doi: 10.1016/j.jbo.2021.100364. eCollection 2021 Aug.
More than 35% of lung adenocarcinoma patients have bone metastases at diagnosis and have a poor survival. Periostin, a carboxylated matrix protein, mediates lung cancer cell dissemination by promoting epithelial-mesenchymal transition, and is involved in bone response to mechanical stress and bone formation regulation. This suggests that periostin may be used as a biomarker to predict survival in lung cancer patients. Serum periostin was assessed at diagnosis in a prospective cohort of 133 patients with lung adenocarcinoma of all stages. Patients were divided into localized and bone metastatic groups. Both groups were matched to healthy controls. Survival analysis and Cox proportional hazards models were conducted in the total population and in bone metastatic group. The median serum periostin level was higher in bone metastatic (n = 67; median: 1752 pmol/L) than in the localized group (n = 66; 861 pmol/L; p < 0.0001). Patients with high periostin (>median) had a poorer overall survival in the whole population (33.3 weeks vs. NR; p < 0.0001) and the bone metastatic group (24.4 vs. 66.1 weeks; p < 0.001). In multivariate analysis, patients with high periostin had increased risk of death (HR = 2.09, 95%CI [1.06-4.13]; p = 0.03). This was also found in the bone metastatic group (HR = 3.62, 95%CI [1.74-7.52]; p = 0.0005). Immunohistochemistry on bone metastasis biopsies showed periostin expression in the bone matrix and nuclear and cytoplasmic staining in cancer cells. Serum periostin was an independent survival biomarker in all-stage and in bone metastatic lung adenocarcinoma patients. IHC data suggest that periostin might be induced in cancer cells in bone metastatic niche in addition to bone microenvironment expression.
超过35%的肺腺癌患者在确诊时已有骨转移,且生存期较短。骨膜蛋白是一种羧化基质蛋白,通过促进上皮-间质转化介导肺癌细胞扩散,并参与骨骼对机械应力的反应和骨形成调节。这表明骨膜蛋白可用作预测肺癌患者生存期的生物标志物。在一个包含133例各期肺腺癌患者的前瞻性队列中,在确诊时评估了血清骨膜蛋白水平。患者被分为局限性和骨转移组。两组均与健康对照进行匹配。在总体人群和骨转移组中进行了生存分析和Cox比例风险模型分析。骨转移组(n = 67;中位数:1752 pmol/L)的血清骨膜蛋白中位数水平高于局限性组(n = 66;861 pmol/L;p < 0.0001)。骨膜蛋白水平高(>中位数)的患者在总体人群(33.3周对未达到;p < 0.0001)和骨转移组(24.4周对66.1周;p < 0.001)中的总生存期较差。在多变量分析中,骨膜蛋白水平高的患者死亡风险增加(HR = 2.09,95%CI [1.06 - 4.13];p = 0.03)。在骨转移组中也发现了这一情况(HR = 3.62,95%CI [1.74 - 7.52];p = 0.0005)。骨转移活检的免疫组化显示骨膜蛋白在骨基质中表达,在癌细胞中呈核染色和胞质染色。血清骨膜蛋白是各期和骨转移肺腺癌患者的独立生存生物标志物。免疫组化数据表明,除了在骨微环境中表达外,骨转移龛中的癌细胞可能也会诱导骨膜蛋白表达。