Pentraxin-3 Is a Novel Biomarker of Lung Carcinoma

Abstract

Purpose: Our objective was to validate the performance of three new candidate lung cancer biomarkers, pentraxin-3 (PTX3), human kallikrein 11 (KLK11), and progranulin.Experimental Design: We analyzed by commercial ELISA, and with a blinded protocol, 422 samples from 203 patients with lung carcinoma, 180 individuals with high risk for lung cancer (heavy smokers), and 43 individuals with cancers other than lung. All samples were obtained from the Early Detection Research Network (Reference set A).Results: We found that progranulin and KLK11 were not informative lung cancer biomarkers, with areas under the receiver operating characteristic curve (AUC; ROC), close to 0.50. However, PTX3 was an informative lung cancer biomarker, with considerable ability to separate lung cancer patients from highrisk controls. At 90% and 80% specificity, the sensitivities versus the high-risk control group were 37% and 48%, respectively. The discriminatory ability of PTX3 was about the same with all major subtypes and histotypes of lung cancer. The AUC of the ROC curves increased according to the disease stage, from 0.64 (stage I) to 0.72 (stage IV).Conclusion: PTX3, but not KLK11 or progranulin, is a new serum biomarker for lung carcinoma. Its diagnostic sensitivity and specificity is similar to other clinically used lung cancer biomarkers. More studies are needed to establish if PTX3 has clinical utility for lung cancer diagnosis and management.

Pentraxin 3: A Novel Biomarker for Predicting Progression from Prostatic Inflammation to Prostate Cancer

“…The potential role of PTX3 as a tissue and serum marker of carcinogenesis was recently postulated for human soft tissue liposarcoma (25) and lung carcinoma (20). Serum PTX3 elevation in patients with cancer are not well understood, but its known overexpression by endothelial cells and macrophages in response to inflammatory signals as well as its role in clearance of cells undergoing apoptosis (14) both suggest that PTX3 may act as a biomarker for neoplasia, through its elevation in the inflammatory microenvironment of the tumor and in the clearance of apoptotic cells (14).…”

“…Unlike short pentraxins, such as C-reactive protein (CRP), PTX3 is not produced by hepatocytes but synthesized by a variety of cell types at the site of inflammation (14,19), whereby it seems to regulate complement activation (14,17,18). Recent findings suggest an insidious relationship between complement and cancer in terms of cellular proliferation and regeneration as well as angiogenesis (18,20).…”

Betulinic Acid Decreases Specificity Protein 1 (Sp1) Level via Increasing the Sumoylation of Sp1 to Inhibit Lung Cancer Growth

“…Because of the difficulty of confirming the roles of all Sp1-regulated genes identified by the microarray analysis, we examined proliferation-related genes that were potentially regulated by Sp1 to elucidate the contributions of Sp1-regulated genes to tumor growth. Among the 68 Sp1-regulated genes related to proliferation, seven genes, namely, Aldh3a1, Arg1,Cd9,Ptx3,Tacstd2,Tpx2, and Vav1, have been reported to be overexpressed in lung tumors or to be biomarkers for the diagnosis of lung cancer (Shimada et al, 2005;Ma et al, 2006;Moreb et al, 2008;Lazer et al, 2009;Rotondo et al, 2009;Kohmo et al, 2010;Diamandis et al, 2011). In addition, Ctsz, Il18, Il4ra, Lcn2, Ntrk3, and Ros1 have been shown to be involved in tumor growth and cancer pathogenesis (Wood et al, 2006;Todaro et al, 2008;Berger et al, 2010;Sevenich et al, 2010;Rovina et al, 2011).…”

Serum-based protein biomarkers for detection of lung cancer

“…The diagnostic sensitivity of pentraxin at 100% specificity was found to be 68%. In a recent study, Diamandis et al [153] confirmed Pentraxin-3 but not KLK11 or progranulin as a new serum biomarker for lung carcinoma. Pentraxin-3 was able to discriminate lung cancer patients from high-risk controls with moderate sensitivity (37% at 90% specificity and 48% at 80% specificity), which was comparable to other currently used lung cancer biomarkers.…”