fibrinopeptide-a and Adenocarcinoma

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

The preoperative plasma levels of fibrinopeptide A (FPA), D-dimer (DD), and von Willebrand Factor (vWF) were measured in 38 patients with cervical cancer undergoing radical hysterectomy with pelvic lymphadenectomy. The surgical-pathological stage of disease was Ib in 17 patients, IIa in 9 patients, and IIb in 12 patients. The tumor size was < or = 4 cm in 20 patients and > 4 cm in 18 patients. The histologic type was squamous cell carcinoma in 32 patients and adenocarcinoma in 6 patients. Positive pelvic lymph nodes were found in 10 patients. When compared to controls, FPA, DD, and vWF levels were significantly raised in patients with surgical-pathological stage IIb disease but not in patients with stage Ib or IIa disease. The values of FPA, DD, and vWF were related to surgical-pathological stage (stage IIb vs stage Ib-IIa: P < 0.005, P < 0.001, and P < 0.001, respectively) and tumor size (> 4 cm vs < or = 4 cm: P < 0.05, P < 0.005, and P < 0.02, respectively), but not to histologic type. vWF values were also related to lymph node status (positive vs negative lymph nodes: P < 0.02). FPA and DD levels were higher in patients with positive lymph nodes than in patients with negative lymph nodes, but the difference did not reach the statistical significance even due to the small number of patients involved. In conclusion, increased fibrin production and degradation seem to occur in patients with stage IIb cervical cancer. The biological meaning of this hemostasis activation deserves further investigation.

Topics: Adenocarcinoma; Adult; Aged; Analysis of Variance; Carcinoma, Squamous Cell; Female; Fibrin Fibrinogen Degradation Products; Fibrinopeptide A; Humans; Hysterectomy; Lymphatic Metastasis; Middle Aged; Neoplasm Staging; Uterine Cervical Neoplasms; von Willebrand Factor

The prompt reduction of elevated fibrinopeptide A (FPA) levels (normal less than 1.3 pmole/ml) by heparin therapy in patients with thromboembolism suggests that measuring the FPA level may provide a good index of disease activity and be a useful method of monitoring therapy. Sepsis or malignancy may elevate FPA levels and coexist with thromboembolism. FPA levels were surveyed in 51 patients with thromboembolism (including 15 with concurrent sepsis or malignancy) during heparin treatment in an attempt to distinguish the effects of coexistent disease and the progression of thromboembolism. The anticoagulant effect of heparin was within the therapeutic range for 81% of the study period. In patients with thromboembolism alone and marked resolution of emboli on repeat lung scan, the mean daily FPA levels were lower than the values in patients with minimal resolution (p less than 0.005). In patients with marked resolution of pulmonary embolism or venous thrombosis and a concurrent disorder, the mean FPA level remained elevated compared to normal values in patients with thromboembolism alone. These results suggest that FPA levels monitored during heparin therapy of thromboembolism may be useful as an index of disease activity except in the presence of coexisting sepsis or malignancy.

Topics: Adenocarcinoma; Adult; Aged; Anticoagulants; Carcinoma, Squamous Cell; Female; Fibrinogen; Fibrinopeptide A; Heart Failure; Heparin; Humans; Leukemia, Lymphoid; Lupus Erythematosus, Systemic; Male; Middle Aged; Polycythemia Vera; Pulmonary Embolism; Sepsis; Thromboembolism