Prognostic and diagnostic potential of local and circulating levels of pentraxin 3 in lung cancer patients

Abstract

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.Despite advancements in surgery, anesthesiology and the improvement of chemotherapy and radiotherapy regimens, the prognosis for clinically detected lung cancer remains dismal, with overall 5-year survival rates of 5-15%. Even with early-stage disease 30-40% of the patients ultimately relapse and die, 1 suggesting that sophisticated biological mechanisms affect their outcome that are not reflected by pathological stage alone. For such a reason, prognostic markers independent of stage are actively sought.In the last few years, leukocyte counts and blood levels of several inflammation markers have been correlated with lung cancer prognosis 2 or investigated as lung cancer risk predictors. 3,4 The role of inflammation in cancer pathogenesis and progression-that has long been investigated-includes the generation of reactive oxygen/nitrogen species and the secretion of cytokines, chemokines and proangiogenic factors. [5][6][7][8] In lung cancer, in addition to smoking-the predominant risk factor-inflammatory conditions such as chronic obstructive pulmonary disease, 9 pulmonary fibrosis and chronic lung infections 10,11 as well as polymorphisms of inflammatory genes 12 are all associated with an increased risk.

Preoperative methylprednisolone increases plasma Pentraxin 3 early after total knee arthroplasty: a randomized, double-blind, placebo-controlled trial

“…Fig. In this context, the previous demonstration of PTX3 to correlate with severity of disease [25] in patients with cardiovascular disease [20,26], cancer [27], acute respiratory distress syndrome [28] and sepsis [17,29,30] should be interpreted carefully, as it may not imply that PTX3 contributes to morbidity, but rather reflect the body's anti-inflammatory response to disease. Comparison of the adjusted means for pentraxin-3 (PTX3) and C-reactive protein (CRP) concentrations.…”

Inflammatory biomarkers and cancer: CRP and suPAR as markers of incident cancer in patients with serious nonspecific symptoms and signs of cancer

“…To our knowledge, this is the first study investigating the association between MBL, ficolin‐1–3 and pentraxin‐3 with incident cancer in a group of NSSC patients. Several studies have previously found an association between increased levels of these biomarkers and various organ‐specific cancers . For example, pentraxin‐3 levels have been found to be associated with lung cancer, gliomas and prostate cancer, and high pentraxin‐3 expression was found to be associated with poor survival in lung cancer .…”

“…Several studies have previously found an association between increased levels of these biomarkers and various organ‐specific cancers . For example, pentraxin‐3 levels have been found to be associated with lung cancer, gliomas and prostate cancer, and high pentraxin‐3 expression was found to be associated with poor survival in lung cancer . Similarly, ficolin‐1 (M‐ficolin) has been associated with colorectal cancer, and serum concentrations of ficolin‐2 (L‐ficolin) and ficolin‐3 (H‐ficolin) have been found to be increased in patients with malignant ovarian tumors compared to benign tumors or normal ovaries .…”

Pentraxins in the activation and regulation of innate immunity

“…In humans, PTX3 expression is increased in different cancers, including glioma, lung cancer, liposarcoma, prostate and pancreatic carcinoma, and breast cancer . PTX3 gene polymorphisms are associated with circulating levels of the protein and risk to develop hepatocellular carcinoma in subjects infected with hepatitis C virus .…”