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Evaluation Of Plasma Lysophospholipids For Diagnostic Significance In The Early Gastric Carcinoma

Posted on:2009-09-19Degree:MasterType:Thesis
Country:ChinaCandidate:X F QiaoFull Text:PDF
GTID:2144360242980468Subject:Clinical Medicine
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Tumor Diagnosis and Treatment have became the front and major issues in the field of modern life science research. According to clinical data ,tumor metastasis is an important cause of death in patients .So the early diagnosis of cancer is essential to tumor treatment. In recent years studies have shown that, as an important factor of biological activity and cell metabolites , the Lysophospholipids such as LPA, LPC, S1P and SPC, and so on, through a variety of signal transduction pathway caused extensive biological effects. A recent study found that lysophosphatidic acid play an important role in tumor development, yet considered as the potential biomarkers of the early diagnosis of tumor.LPA has been proposed as a sensitive biomarker .However, studies investigating the utility of LPA as a biomarker for early detec-tion of ovarian cancer have yielded conflicting results. Preliminary findings from a study, which included 48 healthy controls and 48 women with ovarian cancer, showed that plasma LPA levels were elevated in patients with ovarian cancer (P < 0.01). Importantly, elevated levels were detected in early-stage ovarian cancers compared with controls .The study also compared available CA 125 values with LPA levels, and results suggested that plasma LPA may be a more sensitive marker for ovarian cancer, particularly for stage I disease . However, in another study where LPA levels were measured in plasma samples from 32 patients with ovarian cancer and 32 healthy controls using a liquid chromatography/mass spectroscopy assay, results showed no significant elevation in plasma LPA levels in ovarian cancer patients compared with controls, raising questions about the utility of plasma LPA levels for early detection of ovarian cancer .LPC, a related lysophospholipid (LPL) to LPA, has been shown to displaysignaling properties in cellular systems and to take part in the tumor development and metastasis. Thus, LPC may also have utility as a biomarker of tumor. And data suggest that measuring LPC in addition to LPA may increase the sensitivity and/or specificity of the test .Our study aims to determine for the early diagnosis of gastric cancer bioactive lipid molecular markers, to establish the early screening and diagnosis model of gastric cancer and to explore the possible mechanism,according to detect the level of plasma lysophospholipid of patients with gastric cancer.From August 2007 to January 2008,to collect 25 patients with gastric cancer and to test preoperative plasma lysophosphatidic level; 17 patients with benign ulcer ,24 cases of healthy people as a control, and do the same test.All cases are pathological diagnosis,except for two cases of gastroscopy pathological diagnosis. All case of experimental group have ,preoperatively,no radiotherapy, chemotherapy, inflammation and other complications,while healthy control group have no surgical and medical complications. The main process is follows as: Whole blood samples (5ml)were obtained preoperatively in EDTA tubes by routine venipuncture of patients undergoing surgery,Centrifugated at 1750*g for 15 minutes. the supernatant was transferred to silicide 1.5 ml Eppendorf tubes, (Ice operation), -80°C preservation. Using Optimized chloroform - methanol to extract lipid ;using high pressure liquid chromatography reverse the extract obtained to separate lipid molecules further; using Electro - spray ionization mass spectrometry (ESI-MS, tandem mass spectrometry triple 4)-based technologies, to detct quantitatively LPA, LPC, and other bioactive lipid molecules. Statistical analysis of the results found that in gastric cancer group the level of plasma total LPA ,16:0- LPA and 18:1-LPA are significantly higher than that in control,while Plasma 18:1-LPA is lower. Taking the total LPA and 18:1 - LPC/18 :2-LPC ratio as the standards of diagnosing gastric cancer, the sensitivity was 83.6% and 86.4%, specificity were 71.4 and73.7%, respectively.We believe that through this study lysophosphatidic such as LPA, LPC, and S1P play an important role in the proliferation and metastasis of gastric cancer cell. The mechanism may be through a variety of signaling pathways to promote tumor cell proliferation and promote adhesion, invasion, as well as induce apoptosis disorders. Plasma LPA, LPC, and other LPL levels of gastric cancer can be used as a marker of early diagnosis. Further multi-center study with large samples, Clinical application is geat significant to the survival rate of patients with gastric cancer and clinical principles. In addition, further study of detecting lysophospholipid, blocking lysophospholipid metabolismand inhibiting lysophosph- atidic mediated signal transduction, is expected to become the diagnosis and treatment of tumors in the new direction.
Keywords/Search Tags:Lysophospholipid, gastric cancer, diagnosis
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