fibrinopeptide-a and Stomach-Neoplasms

We aimed to identify serum level variations in protein-derived peptides between patients diagnosed with gastric adenocarcinoma (GAC) and non-cancer persons (control) to detect the activity changes of proteases and explore the auxiliary diagnostic value in the context of GAC physiopathology.. The label-free quantitative peptidome approach was applied to identify variants in serum levels of peptides that can differentiate GAC patients from the control group. Peptide sequences were submitted against Proteasix tool predicting proteases potentially involved in their generation. The activity change of proteases was subsequently estimated based on the peptides with significantly altered relative abundance. In turn, activity change prediction of proteases was correlated with relevant protease expression data from the literature.. A total of 191 peptide sequences generated by the cleavage of 36 precursor proteins were identified. Using the label-free quantification approach, 33 peptides were differentially quantified (adjusted fold change ≥ 1.5 and p-value < 0.05) in which 19 were up-regulated and 14 were down-regulated in GAC samples. Of these peptides, fibrinopeptide A was significantly decreased and its phosphorylated form ADpSGEGDFLAEGGGVR was upregulated in GAC samples. Activity change prediction yielded 10 proteases including 6 Matrix Metalloproteinases (MMPs), Thrombin, Plasmin, and kallikreins 4 and 14. Among predicted proteases in our analysis, MMP-7 was presented as a more promising biomarker associated with useful assays of clinical practice for GAC diagnosis.. Our experimental results demonstrate that the serum levels of peptides were significantly differentiated in GAC physiopathology. The hypotheses built on protease regulation could be used for further investigations to measure proteases and their activity levels that have been poorly studied for GAC diagnosis.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Amino Acid Sequence; Biomarkers, Tumor; Cohort Studies; Computer Simulation; Female; Fibrinopeptide A; Humans; Male; Matrix Metalloproteinase 7; Middle Aged; Principal Component Analysis; Protein Interaction Maps; Proteome; Serine Endopeptidases; Stomach Neoplasms

Gastric cancer is one of the leading causes of tumor-related deaths in China. The tumor, node, metastasis (TNM) classification system is useful for predicting clinical prognosis of patients with gastric cancer. However, determining the presence of lymph node involvement in the early stages of gastric cancer is difficult without biopsy. Therefore, it is necessary to identify novel serum biomarkers for TNM cancer staging and prognostic follow-up. In this study, we have reported fibrinopeptide-A (FPA) with alanine truncation at the N-terminal as a novel biomarker to differentiate gastric cancer with and without lymph node metastases. We analyzed 369 individual serum samples including gastric cancer patients without lymph node metastases (n = 33), gastric cancer patients with lymph node metastases (n = 157; confirmed by pathology), and age- and sex-matched healthy individuals (n = 179). The data showed that 85.4% of patients with lymph node metastases were positive for FPA with alanine truncation at the N-terminal (degAla-FPA, 1,465.63 Da), as determined by tandem mass spectrometry (MS). Using degAla-FPA as the biomarker, the sensitivity was 85.4% for gastric cancer patients with lymph node metastases, and the specificity was 100% for gastric cancer patients without lymph node metastases. The high sensitivity and specificity achieved with serum degAla-FPA levels indicated that MS technology could facilitate the discovery of a novel and quantitative prognostic biomarker for gastric cancer with lymph node involvement.

Topics: Biomarkers, Tumor; Case-Control Studies; Fibrinopeptide A; Humans; Lymphatic Metastasis; Neoplasm Invasiveness; Neoplasm Staging; Peptide Fragments; Predictive Value of Tests; Prognosis; Proteomics; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Stomach Neoplasms; Tandem Mass Spectrometry

Gastric cancer is the second most common malignancy and prognosis remains dismal. The reasons for the poor prognosis are the lack of sensitive serum markers for early detection and screening of high-risk individuals as well as the limited treatment options in advanced cancer stages. Using MALDI-TOF mass spectrometry after prefractionation of sera with magnet hydrophobic C8 coated beads sera from 14 patients with gastric cancer and 14 healthy controls mass spectra were generated. A peptide fragment was found to be highly elevated in cancer sera and was identified as fibrinopeptide A. To confirm proteome analysis of gastric cancer sera, we then screened a larger series of patients with gastric cancer (n = 99), high-risk individuals (n = 13) and normal controls (n = 111) for fibrinopeptide A serum levels. Interestingly, the mean logarithmic concentrations of serum fibrinopeptide A levels were significantly higher in cancer patients (mean 3.636 +/- 0.3738; p < 0.0001) and high-risk individuals (mean 3.569 +/- 0.4722; p < 0.05) compared to normal controls (mean 3.303 +/- 0.4012). In contrast, we observed no association of fibrinopeptide A levels with tumor stage, tumor location, presence of regional or distant metastasis, and Lauren type of gastric cancer. In conclusion, MALDI-TOF mass spectrometry of prefractionated gastric cancer sera allows the identification of potential biomarkers that may lead to the development of serum based tests for screening of high-risk individuals.

Topics: Aged; Amino Acid Sequence; Biomarkers; Female; Fibrinopeptide A; Humans; Magnetics; Male; Middle Aged; Molecular Sequence Data; Neoplasm Proteins; Serum; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Stomach Neoplasms

The origin of coagulation and fibrinolysis abnormalities in cancer patients is unknown. The aim of this study was to measure markers of coagulation and fibrinolysis in portal and peripheral blood from patients with and without gastric malignancy.. Blood samples were drawn from the portal vein and a peripheral vein in 39 patients undergoing elective gastric surgery, 18 for gastric malignancy and 21 for benign disorders, and analyzed for prothrombin fragment 1 + 2 (F1 + 2), thrombin-anti-thrombin III complex (TAT), fibrinogen and fibrin degradation products (FgDP, FbDP), and fibrinopeptide A (FpA).. In portal blood, levels of F1 + 2, TAT, FpA, FgDP, and FbDP did not differ in the two groups. In peripheral blood, levels of FpA and FbDP were higher in cancer patients, but in a multiple regression model malignancy did not contribute significantly to variation in peripheral FpA or FbDP levels. In both groups FpA levels were higher in portal blood than in peripheral blood.

Topics: Antithrombin III; Blood Coagulation; Female; Fibrin Fibrinogen Degradation Products; Fibrinolysis; Fibrinopeptide A; Humans; Male; Middle Aged; Peptide Fragments; Peptide Hydrolases; Portal Vein; Prothrombin; Stomach Neoplasms

CEA, GICA, TPA, Fibrinopeptide-A (FpA) and Gamma-GT serum levels were evaluated in 312 patients affected by gastric cancer, to assess their effectiveness in diagnosis, evaluation of disease extension and follow-up of gastric cancer. In 204 patients neoplasia was limited to the stomach, in 108 liver metastases, ascertained by ultrasonography and/or TAC, were present. CEA was increased in 224 cases (71.8%); mean values were significantly higher in metastatic patients than in metastasis-free group (p less than 0.001), but overlap of values between the two groups was observed in about one third of cases. GICA was increased in 268 patients (86%) and TPA in 306 (98%), without significant differences between metastatic and metastasis-free group. FpA was increased in all patients; when metastases were present it was significantly higher than in metastasis-free patients (p less than 0.001), with negligible overlap of values between the two groups. Gamma-GT was normal in 202 metastasis-free patients (99%) and increased in 105 patients with liver metastases (97%). On the basis of these data CEA does not seem to have striking diagnostic sensibility nor reliability in differentiating presence from absence of liver metastases in patients with gastric cancer. Combined assay of TPA, FpA and Gamma-GT seems to be the most reliable serological approach in diagnosis, staging and follow-up of gastric cancer.

Topics: Adult; Aged; Aged, 80 and over; Antigens, Neoplasm; Biomarkers, Tumor; Carcinoembryonic Antigen; Female; Fibrinopeptide A; gamma-Glutamyltransferase; Humans; Liver Neoplasms; Male; Middle Aged; Peptides; Radioimmunoassay; Stomach Neoplasms; Tissue Polypeptide Antigen

In 12 patients with gastric cancer and in 14 with large bowel neoplasia, classified according to the TNM system, some major blood indices of hemostasis, platelet activation and fibrinolysis were assessed before and for 1 month after surgery, to show whether possible variations of such indices may provide useful clues to follow-up, treatment effectiveness and prognosis. The following conclusions may be drawn: (1) the assay of platelets, fibrinogen, AT III, fibrin(ogen) degradation products, fragment X, platelet factor 4 has provided useful clues in neither group of patients; (2) preoperative high beta-thromboglobulin (beta-TG) is a reliable index of tumor presence in both gastric and large bowel cancer; (3) postoperative high beta-TG and fibrinopeptide A (FpA) are reliable indices of (a) tumor persistence in both gastric and large bowel cancer; (b) lymph node involvement in gastric much more than in large bowel cancer; (c) metastatic spreading from gastric cancer; (4) the FpA levels are proportional to the tumor mass in gastric cancer. The finding of lower plasma heparin levels in neoplastic patients, when compared with controls (20 patients having undergone abdominal surgery for extraneoplastic affections) suggests higher than conventional doses (5,000 units every 8 h s.c.) of the drug should be given to neoplastic patients in order to prevent thromboembolic bouts and possibly reduce metastatic spreading.

Topics: Adult; Aged; Aged, 80 and over; beta-Thromboglobulin; Blood Coagulation; Colonic Neoplasms; Female; Fibrin Fibrinogen Degradation Products; Fibrinopeptide A; Heparin; Humans; Male; Middle Aged; Neoplasm Staging; Prognosis; Stomach Neoplasms

Serial changes of FPA, FPB beta 15-42, FN, XIIIa, and alpha 2PI were investigated for the study on wound healing, blood coagulation, and fibrinolysis during gastric cancer surgery. For a control, we compared the preoperative values with the postoperative ones. These results also were compared with the values in healthy volunteers and in patients with cholelithiasis or myoma uteri. Our findings were as follows; 1) Compared with the control values, a statistically significant elevation of FPA, FPB beta 15-42 and FPA/FPB beta 15-42 ratios in patients with gastric cancer was noticed after operation. 2) Compared with the control values, a statistically marked decrease of FN, XIIIa and alpha 2PI in patients with gastric cancer was observed after operation. 3) The preoperative FPA and FPB beta 15-42 levels of gastric cancer patients were appreciably greater than those of normal healthy volunteers. Compared with patients with cholelithiasis or myoma uteri, however, the only preoperative FPA of gastric cancer patients showed significantly high levels. 4) FN and alpha 2PI revealed a notable positive correlation. These results suggest (1) increase of coagulation activity (thrombin formation) in gastric cancer patients; (2) increase of intravascular coagulation and fibrinolytic activity (thrombin and plasmin formation) during gastric cancer surgery; and, (3) depression of FN, XIIIa and alpha 2PI during surgery was due to sequestration at the site of tissue injury.

Topics: Adult; Aged; alpha-2-Antiplasmin; Blood Coagulation; Cholelithiasis; Factor XIII; Female; Fibrin Fibrinogen Degradation Products; Fibrinolysis; Fibrinopeptide A; Fibrinopeptide B; Fibronectins; Humans; Intraoperative Period; Leiomyoma; Male; Middle Aged; Peptide Fragments; Stomach Neoplasms; Transglutaminases; Uterine Neoplasms; Wound Healing

Plasma Fibrinopeptide A (FPA) and beta-thromboglobulin (beta-TG) were measured in patients with various thrombogenic diseases. Plasma FPA levels were also measured in patients with malignant neoplasm and in patients who had open heart surgery. The following results were obtained. Measurement of FPA using Bentonite absorption method was simple and sensitive for clinical application. Plasma FPA and beta-TG levels were elevated in various thrombogenic diseases. Plasma FPA level correlated neither with plasma beta-TG level nor with plasma fibrinogen level. Measurement of FPA is a useful tool in the diagnosis of thromboembolic diseases, and is more trustworthy when combined with beta-TG measurement. Diagnosis of thromboembolism may be made when FPA levels are over 5 ng/ml or beta-TG over 50 ng/ml. Diagnosis of venous thrombosis was possible by the assay of FPA with a sensitivity of 100 per cent. Diagnosis of arterial thrombosis was made by the assay of beta-TG with a sensitivity of 64 per cent. In patients with gastric cancer, levels of plasma FPA tended to correlate with the size of the tumor, indicating that the progression and the activity of the tumor may be estimated by plasma FPA levels. The mean FPA level at the late stage of cardiopulmonary bypass was 14.2 +/- 6.8 ng/ml, indicating that fibrinogen is consumed during the bypass despite the systemic heparinization.

Topics: Adult; Aged; beta-Thromboglobulin; Cardiopulmonary Bypass; Female; Fibrinogen; Fibrinopeptide A; Humans; Male; Middle Aged; Radioimmunoassay; Stomach Neoplasms; Thrombosis