Study Role Of The Chemical Modification Of Transthyretin In The Auxiliary Diagnosis Of Lung Cancer And Pulmonary Infection Diseases

Aims:Lung cancer is the most common malignant tumor of the lung disease which the mortality rate increased year by year and has a similar clinical manifestation with pulmonary infectious diseases. The most common laboratory diagnosis is tumor marker which lack of specificity, so you need to screen other biomarkers. Transthyretin are used as index of nutritional status and infection because of its short half-life and mainly comes from the liver. Moreover, for TTR gene expression is sensitive for cytokine interleukin1, interleukin6and tumor necrosis factor, known as the acute negative phase reaction protein. This study was to explore pleural effusion and serum TTR Chemical modification, joint clinical biomarkers to screen the differential diagnosis of lung cancer and pulmonary infection disease to guide the laboratory diagnosis of lung cancer and pulmonary infection.Methods:(1) Collect serum and pleural effusion of lung cancer (95cases, including35squamous cell lung cancer,30glandular cell lung cancer and30small cell lung cancer), pulmonary infection diseases (22cases, including10patients with suppurative pulmonary infectious diseases and12pulmonary tuberculosis) used to measure biochemical content and TTR mass spectrometry analysis. Also collect serum of50healthy control people which used to measure biochemical markers and TTR mass spectrometry analysis.(2) Use TOSHIBA TBA-120FR type full automatic biochemical analyzer to detect triglyceride (TG), total cholesterol (TC), total protein (TP), albumin(Alb), glucose (Glu), adenosine (ADA) and lactate dehydrogenase (LDH) in serum and pleural effusion.(3) Use TOSHIBA TBA-40automatic analyzer to detect ApoB, ApoA-1and TTR in serum and pleural effusion.(4) Use Roche2010type automatic electrochemical luminescence immune detection analyzer to detect CYFRA-21and NSE. Use Abbott ARCHITECTi2000SR automatic chemiluminescence immune analyzer to detect CEA, CA125and CA199levels.(5) By MALDI-TOF-MS analysis of healthy controls respectively, lung cancer and pulmonary infection group of serum and pleural effusion in TTR protein modification, and calculate the modified ratio.Results:The first part:To explore the role of TTR in the auxiliary diagnosis of lung cancer(1) Lung cancer serum tumor markers CEA, CYFRA-21, CA125, CA199and NSE levels were significantly higher than healthy control group, the positive rate between13.3%and48.6%, and differences between the pathological types. Commonly used joint detection to improve the detection rate, but found the more overlay the lower positive rate. Two joint detection in the group of squamous carcinoma, adenocarcinoma and small cell lung cancer group were greater than80%sensitivity, three joint detection sensitivity is more than70%in the squamous carcinoma group, in adenocarcinoma group sensitivity is greater than60%, and the four and five determination of tumor markers combined the positive detection rate decreased significantly.(2) Biochemical index in pleural effusion compare with in serum of lung cancer group, there are six indexes have a statistically significant difference (P<0.05), lipid and lipoprotein components in pleural effusion lower than in serum, followed by protein targets and TTR was most evident difference. The ratio of LDH is rise but have no statistically difference.(3) In serum and pleural effusion of lung cancer group and healthy control group, we found four TTR protein peaks, including three major types of chemical modification and cysgly-TTR modification type proportion in the pleural effusion in lung cancer is higher than in serum of lung cancer group and healthy control group.The second part:Study on auxiliary examination index in identification of lung cancer and pulmonary infection disease(1) Comparison between lung cancer and pulmonary infection in patients with serum biomarkers, we found TC, ApoA-1and TTR have significant differences, and lung cancer group significantly higher than the pulmonary infection group. In pleural effusion there are only TTR and ADA existing significant differences.(2) Analysis TTR chemical modification in serum and pleural effusion of lung cancer and pulmonary infection group, we found that in lung cancer, both in serum and pleural effusion there exist sul-TTR, cys-TTR and cysgly-TTR modification; But group of pulmonary infection appeared only sul-TTR and cys-TTR two peaks.Conclusion:(1) Joint detection of serum CEA, CYFRA-21, CA125, CA199and NSE can improve detection rate in lung cancer patients. Superposition of item by item can improve specificity but reduce sensitivity. However, considering joint three indexs detection is suitable for identification of lung cancer and pulmonary infection group.(2) TTR expresses difference in content in serum and pleural effusion between Lung cancer and and lung infection group which could be a index in assistant to diagnose the two groups.(3) In serum and pleural effusion of lung cancer, there are three TTR chemical modification types including sul-TTR, cys-TTR and cysgly-TTR. But only cysgly-TTR is higher than pulmonary infection obviously which can be used as auxiliary diagnostic indicator of lung cancer and pulmonary infection disease.