Infante Maurizio, Allavena Paola, Garlanda Cecilia, Nebuloni Manuela, Morenghi Emanuela, Rahal Daoud, Roncalli Massimo, Cavuto Silvio, Pesce Samantha, Monari Marta, Valaperta Serenella, Montanelli Alessandro, Solomon Daniel, Bottoni Edoardo, Errico Valentina, Voulaz Emanuele, Bossi Manuela, Chiesa Giuseppe, Passera Eliseo, Mantovani Alberto, Alloisio Marco
Thoracic Surgery Department, Humanitas Research Hospital, Rozzano, Milano, Italy.
Humanitas Research Center, Rozzano, Milano, Italy.
Int J Cancer. 2016 Feb 15;138(4):983-91. doi: 10.1002/ijc.29822. Epub 2015 Sep 8.
There is a well-established link between inflammation and cancer of various organs, but little data are available on inflammation-associated markers of diagnostic and prognostic clinical utility in pulmonary malignancy. Blood samples were prospectively collected from 75 resectable lung cancer patients before surgery and in a cohort of 1,358 high-risk subjects. Serum levels of long pentraxin 3 (PTX3) were determined by high-sensitivity ELISA. PTX3 immunostaining was evaluated by immunohistochemistry in cancer tissue. Serum PTX3 levels in the high-risk population were not predictive of developing subsequent lung cancer or any other malignancy; however, serum PTX3 values in patients with lung cancer were significantly higher compared with cancer-free heavy smokers. With a cutoff of 4.5 ng/ml, specificity was 0.80, sensitivity 0.69, positive predictive value 0.15 and negative predictive value 0.98. The receiver operating curve (ROC) for serum PTX3 had an area under the curve (AUC) of 83.52%. Preoperative serum PTX3 levels in lung cancer patients did not correlate with patient outcome, but high interstitial expression of PTX3 in resected tumor specimens was a significant independent prognostic factor associated with shorter survival (p < 0.001). These results support the potential of serum PTX3 as a lung cancer biomarker in high-risk subjects. Furthermore, PTX3 immunohistochemistry findings support the role of local inflammatory mechanisms in determining clinical outcome and suggest that local expression of PTX3 may be of prognostic utility in lung cancer patients.
炎症与各器官癌症之间存在已被充分证实的联系,但关于肺部恶性肿瘤中具有诊断和预后临床效用的炎症相关标志物的数据却很少。前瞻性地收集了75例可切除肺癌患者术前的血样以及1358名高危受试者的血样。通过高灵敏度酶联免疫吸附测定法测定血清长五聚体3(PTX3)水平。通过免疫组织化学评估癌组织中的PTX3免疫染色。高危人群的血清PTX3水平不能预测随后发生肺癌或任何其他恶性肿瘤;然而,肺癌患者的血清PTX3值与无癌的重度吸烟者相比显著更高。以4.5 ng/ml为临界值,特异性为0.80,灵敏度为0.69,阳性预测值为0.15,阴性预测值为0.98。血清PTX3的受试者工作特征曲线(ROC)的曲线下面积(AUC)为83.52%。肺癌患者术前血清PTX3水平与患者预后无关,但切除的肿瘤标本中PTX3的高间质表达是与较短生存期相关的显著独立预后因素(p < 0.001)。这些结果支持血清PTX3作为高危受试者肺癌生物标志物的潜力。此外,PTX3免疫组织化学结果支持局部炎症机制在决定临床结局中的作用,并表明PTX3的局部表达可能对肺癌患者具有预后效用。