Transthyretin as a potential biomarker for the differential diagnosis between lung cancer and lung infection

Abstract

Abstract. Satisfactory biomarkers for screening and early diagnosis of lung cancer remain scarce and require further investigation. The aim of the present study was to examine the changes of the biochemical and protein composition in the serum and pleural effusion from lung cancer and lung infection (bacterial pneumonia) patients. A total of 92 patients with lung cancer, 38 with bacterial pneumonia and 42 healthy controls were enrolled in the study. The serum levels of cholesterol, apolipoprotein A and transthyretin (TTR) in the lung cancer patients were higher than that of the lung infection patients (P<0.05). The levels of TTR were higher, whereas the activity of adenosine deaminase (ADA) was lower in the pleural effusion from the lung cancer patients compared to the lung infection patients (P<0.05). Furthermore, the pleural effusion/serum TTR ratios in the lung cancer patients were higher, whereas the ratios of ADA were lower (P<0.05). By matrix-assisted laser desorption/ionization time-of-flight mass spectrometry analysis, four major peaks corresponding to native TTR, Sul-TTR, Cys-TTR and Cysgly-TTR were observed in the serum of the lung cancer and lung infection patients. A significant increase was found in the proportion of Cysgly-TTR in the pleural effusion from the patients with lung cancer. The data indicated that a combination of pleural effusion/serum TTR ratios and modified TTR may be beneficial for the differential diagnosis between lung cancer and lung infection. IntroductionLung cancer is one of the most common malignant tumors worldwide, with a 5-year survival rate of 14% (1). Thus far, the statistics for cancer occurrence and outcome show that lung cancer remains a primary cause of mortality from cancer (2,3). Since the incidence and mortality of lung cancer increases significantly every year, it represents a major economic burden to society. Currently, the screening and early diagnosis of lung cancer in clinics relies mainly on magnetic resonance imaging (MRI) and computed tomography (CT) imaging, whereas the final diagnosis is established on the basis of histopathological examination results. The early clinical manifestations of lung cancer patients are relatively mild and not typical, easily overlooked or confused with benign inflammatory disease, such as lung infection. Therefore, early identification and diagnosis of lung cancer is significant since lung cancer may be curable in its early stages (1).Thus far, increasing attention has focused on searching for improved biomarkers that function not only to detect lung cancer at an early stage but also to explore the molecular mechanisms that underlie cancer development. Tumor markers, including carcinoembryonic antigen (CEA), carbohydrate antigen 125 (CA125), neuron-specific enolase (NSE), squamous cell carcinoma antigen (SCCAg) and cytokeratin-19 fragments (Cyfra21-1), are clinically applied for the early detection of lung cancer (4,5). However, the sensitivity and specificity of these biomarkers are not adequate (6-8). Combined detection usi...

Proteomic pilot study of tuberculosis pleural effusion

“…Previous research has shown the TTR level to be upregulated in the sera of adenocarcinoma lung cancer patients using 2̻DE and MALDI̻TOF̻MS peptide mass fingerprinting [18]. Another recently published Chinese population based study of patients with lung cancer found that both TTR levels in pleural effusion and pleural effusion to serum TTR ratios were higher compared with patients with noncancerous lung infections [19]. These results along with our findings indicate that TTR has the potential to contribute to differential diagnosis among different pleural effusions.…”

Prognostic impact of serum transthyretin in patients with non‑small cell lung cancer

“…TTR correlates with patient outcome in various diseases (6)(7)(8). With regard to lung cancer, TTR has been reported to be useful in distinguishing lung cancer from lung infection (9), and to be synthesized in lung cancer cells (10). Low perioperative serum TTR was reported to predict early recurrence after curative-intent surgery in NSCLC patients (11).…”

Screening and Biosensor-Based Approaches for Lung Cancer Detection

“…Genetic and proteomics-based biomarkers are two major types of biomarkers, which can be identified through tumor cells, urine, sputum, blood, or other body fluids [ 3 ]. Table 3 demonstrates numerous lung cancer markers [ 121 , 122 , 123 , 124 , 125 , 126 , 127 , 128 , 129 , 130 , 131 , 132 , 133 , 134 , 135 , 136 , 137 , 138 , 139 , 140 , 141 ].…”

“…Many types of proteomic biomarkers have been investigated for lung cancer detection, including Annexin II [ 122 ], APOA1 [ 123 ], carcinoembryonic antigen (CEA) [ 124 ], carbohydrate antigen 125 (CA125) [ 125 ], carbohydrate antigen 19-9 (CA19-9) [ 126 ], cytokeratin fragment 21-1 (CYFRA21-1) [ 127 ], CD59 glycoprotein [ 128 ], transthyretin (TTR) [ 129 ], GM2 activator protein (GM2AP) [ 130 ], haptoglobin-R2 [ 131 ], Ig-free light chain [ 132 ], neuron-specific enolase (NSE) [ 133 ], nitrated ceruloplasmin [ 134 ], plasma kallikrein B1 [ 135 ], ProGRP [ 136 ], retinol binding protein (RBP) [ 137 ], squamous cell carcinoma (SCC) [ 138 ], vascular endothelial growth factor (VEGF) [ 139 ], TPA [ 140 ], and tumor M2-pyruvate kinase [ 141 ].…”