Rangel M P, Antonangelo L, Acencio M M P, Faria C S, de Sá V K, Leão P S, Farhat C, Fabro A T, Longatto Filho A, Reis R M, Takagaki T, Capelozzi V L
Departmento de Patologia, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brasil.
Divisão de Pneumologia, Instituto do Coração (Incor), Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brasil.
Braz J Med Biol Res. 2018;51(8):e7138. doi: 10.1590/1414-431x20187138. Epub 2018 May 28.
Cofilin-1 (CFL1), a small protein of 18 kDa, has been studied as a biomarker due to its involvement in tumor cell migration and invasion. Our aim was to evaluate CFL1 as an indicator of malignancy and aggressiveness in sputum samples. CFL1 was analyzed by ELISA immunoassay in the sputum of 73 lung cancer patients, 13 cancer-free patients, and 6 healthy volunteers. Statistical analyses included ANOVA, ROC curves, Spearman correlation, and logistic regression. Sputum CFL1 levels were increased in cancer patients compared to cancer-free patients and volunteers (P<0.05). High expression of sputum CFL1 was correlated to T4 stage (P=0.01) and N stage (P=0.03), tobacco history (P=0.01), and squamous cell carcinoma histologic type (P=0.04). The accuracy of sputum CFL1 in discriminating cancer patients from cancer-free patients and healthy volunteers were 0.78 and 0.69, respectively. CFL1 at a cut-off value of 415.25 pg/mL showed sensitivity/specificity of 0.80/0.70 in differentiating between healthy volunteers and cancer patients. Sputum CFL1 was also able to identify cancer-free patients from patients with lung cancer. The AUC was 0.70 and, at a cut-off point ≥662.63 pg/mL, we obtained 60% sensitivity and 54% specificity. Logistic regression analysis controlled for tobacco history, histologic types, and N stage showed that cancer cell-associated CFL1 was an independent predictor of death. Smoker patients with squamous cell carcinoma, lymph node metastasis and sputum CFL1>1.475 pg/mL showed augmented chance of death, suggesting lung cancer aggressiveness. CFL1 presented diagnostic value in detecting lung cancer and was associated to tumor aggressiveness.
丝切蛋白-1（CFL1）是一种18 kDa的小蛋白，因其参与肿瘤细胞迁移和侵袭而被作为生物标志物进行研究。我们的目的是评估CFL1作为痰液样本中恶性肿瘤和侵袭性指标的价值。通过酶联免疫吸附测定（ELISA）对73例肺癌患者、13例无癌患者和6名健康志愿者的痰液进行CFL1分析。统计分析包括方差分析、ROC曲线、Spearman相关性分析和逻辑回归分析。与无癌患者和志愿者相比，癌症患者痰液中CFL1水平升高（P<0.05）。痰液CFL1高表达与T4期（P=0.01）、N期（P=0.03）、吸烟史（P=0.01）和鳞状细胞癌组织学类型（P=0.04）相关。痰液CFL1区分癌症患者与无癌患者和健康志愿者的准确率分别为0.78和0.69。CFL1临界值为415.25 pg/mL时，区分健康志愿者和癌症患者的敏感性/特异性为0.80/0.70。痰液CFL1也能够区分肺癌患者与无癌患者。曲线下面积（AUC）为0.70，临界值≥662.63 pg/mL时，敏感性为60%，特异性为54%。对吸烟史、组织学类型和N期进行校正的逻辑回归分析表明，癌细胞相关的CFL1是死亡的独立预测因子。患有鳞状细胞癌、有淋巴结转移且痰液CFL1>1.475 pg/mL的吸烟患者死亡几率增加，提示肺癌具有侵袭性。CFL1在检测肺癌方面具有诊断价值，并与肿瘤侵袭性相关。
