Marta Łukaszewicz-Zając

Comparison between clinical significance of serum proinflammatory proteins (IL-6 and CRP) and classic tumor markers (CEA and CA 19-9) in gastric cancer

Gastric cancer (GC) is a second most common cause of cancer-related death and represents an inflammation-driven malignancy. It has been suggested that interleukin 6 (IL-6) and C-reactive protein (CRP) play a potential role in the growth and progression of GC. The aim of the present study was to compare clinical significance of IL-6 and CRP with classic tumor markers—carcinoembryonic antigen (CEA) and carbohydrate antigen (CA 19-9) in GC patients. The study included 92 patients with GC and 70 healthy subjects. The serum concentrations of IL-6, CEA and CA 19-9 were determined using immunoenzyme assays, whereas CRP using immunoturbidimetric method. We defined the diagnostic criteria and prognostic value for proteins tested. In GC patients, the serum concentrations of all the proteins tested were significantly higher than in healthy subjects. The IL-6, CEA and CA 19-9 levels correlated with nodal metastases, while CRP with tumor stage, gastric wall invasion, presence of nodal and distant metastases. Diagnostic sensitivity of IL-6 was higher (85%) than those of other markers (CRP 66%, CA 19-9 34%, CEA 22%) and increased in combined use with CRP or CEA (88%). The area under ROC curve for IL-6 was larger than those of CRP and classic tumor markers (CEA and CA 19-9). None of the proteins tested was independent prognostic factor for the survival of GC patients. Our findings indicate better usefulness of serum proinflammatory proteins—IL-6 and CRP than classic tumor markers—CEA and CA 19-9 in the diagnosis of GC.

Pre-treatment serum and plasma levels of matrix metalloproteinase 9 (MMP-9) and tissue inhibitor of matrix metalloproteinases 1 (TIMP-1) in gastric cancer patients

Abstract Background: The invasion and metastases of gastric cancer (GC) depends on the activities of matrix metalloproteinases and tissue inhibitors of metalloproteinases. It was suggested that the concentration of plasma matrix metalloproteinase-9 (MMP-9) is better than the concentration of serum MMP-9 for prediction of evolution of GC. The aim of the present study was to compare the clinical usefulness of plasma and serum tissue inhibitor of metalloproteinases-1 (TIMP-1) in the diagnosis and prognosis of GC. Methods:Plasma and serum concentrations of TIMP-1, MMP-9 and carcinoembryonic antigen (CEA) were assayed in 73 patients with GC and 61 healthy controls. The diagnostic criteria and prognostic value for the measurands were defined. Results: Plasma and serum TIMP-1, MMP-9 and CEA were significantly higher in GC patients compared with healthy controls. The area under the ROC curve (AUC) (0.961), diagnostic sensitivity (89%) and accuracy (91%) of plasma TIMP-1 were higher than those for MMP-9 and CEA. An increased pre-treatment concentration of plasma TIMP-1 was a significant independent prognostic factor for the survival of patients with GC. Conclusions: These findings suggest that the plasma TIMP-1 is a better biomarker than the serum TIMP-1 and might be useful for the diagnosis of GC and prognosis of patient survival. Clin Chem Lab Med 2009;47:1133–9.

Cerebrospinal fluid leakage—Reliable diagnostic methods

Prompt diagnosis and early treatment of cerebrospinal fluid (CSF) leakage minimizes the risk of severe complications. In patients presenting with clear fluid nasal discharge it is important to identify the nature of the rhinorrhea. The CSF leakage may occur as post-traumatic, iatrogenic, spontaneous or idiopathic rhinorrhea. The differential diagnosis of CSF rhinorrhea often presents a challenging problem. The confirmation of CSF rhinorrhea and localization of the leakage may be diagnosed by CT, MRI cisternography and MRI cisternography in combination with single photon emission tomography or radioisotopic imaging. Although these methods allow estimation of the CSF leakage with high accuracy, they are expensive and invasive procedures. Therefore, biochemical methods are still used in the differentiation. Although the most common diagnostic method for screening CSF leakage is glucose oxidase, its diagnostic sensitivity and specificity is generally unsatisfactory. False negative results may occur with bacterial contamination and false positive results are common in diabetic patients. Glucose detection is not recommended as a confirmatory test. As such, other biomarkers of the CSF leakage, such as beta-2-transferrin (beta-2 trf) and beta-trace protein (betaTP) are necessary to identify and confirm of this condition.

Clinical significance of serum macrophage-colony stimulating factor (M-CSF) in esophageal cancer patients and its comparison with classical tumor markers.

Abstract Background: Hematopoietic growth factors (HGFs), such as macrophage-colony stimulating factor (M-CSF) are produced aberrantly in many malignancies. Esophageal cancer (EC) is characterized by late diagnosis, rapid progression and poor survival. The purpose of the present study was to determine the clinical usefulness of M-CSF in the diagnosis of EC and its histological type – squamous cell cancer of the esophagus (ESCC). Methods: The study included 80 patients with EC (54 with ESCC and 26 with adenocarcinoma of the esophagus) and 30 healthy subjects. The serum concentrations of M-CSF, carcinoembryonic antigen (CEA) and squamous cell cancer antigen (SCC-Ag) were determined using immunoenzyme assays. We defined the percentage of increased concentrations of proteins tested and the areas under the receiver-operating characteristics (ROC) curves. Results: In EC and ESCC patients, serum concentrations of M-CSF, CEA and SCC-Ag were significantly higher compared with healthy subjects. Concentrations of M-CSF in both groups analyzed (EC and ESCC) showed a tendency for increases with depth of tumor invasion, the presence of lymph node and distant metastases. The combined use of M-CSF with SCC-Ag increased their percentage of increased concentrations, and this value was higher than for classical tumor markers in both groups analyzed. The area under ROC curve for M-CSF was larger than for CEA in EC patients. Conclusions: Our findings suggest the potential usefulness of serum M-CSF concentrations as a tumor marker for EC, especially in combination with SCC-Ag. However, the diagnostic value of this cytokine may be limited because of its non-specific nature. Clin Chem Lab Med 2010;48:1467–73.

Comparative evaluation of serum C-reactive protein (CRP) levels in the different histological subtypes of esophageal cancer (squamous cell carcinoma and adenocarcinoma of esophagus).

Elevated C‐reactive protein (CRP) levels have been found in patients with several malignancies. The aim of the present study was to analyze the diagnostic and prognostic values of CRP levels measurement in esophageal cancer (EC) patients in relation to its different histological subtypes (squamous cell carcinoma—ESCC and adenocarcinoma—AC of esophagus) and compared them with classic tumor markers—carcinoembryonic antigen (CEA) and squamous cell cancer antigen (SCC‐Ag). The diagnostic sensitivity, specificity, and the areas under receiver operating characteristic curves (AUC) for all the proteins tested were defined. Serum CRP levels were statistically higher in EC, ESCC, and AC patients compared to healthy subjects and significantly increased in EC and ESCC patients with the presence of lymph node and distant metastases. The percentage of elevated CRP results in all the analyzed subgroups (EC, ESCC, and AC) was higher than CEA and SCC‐Ag, similarly as AUC for CRP in comparison to SCC‐Ag. Serum CRP level was a significant predictor of EC and ESCC patients’ survival in univariate analysis. In conclusion, these results indicate that CRP can be used as an adjunct in evaluating the tumor markers—CEA and SCC‐Ag and may improve the clinical diagnosis and follow‐up of EC patients, especially for ESCC subgroup.

The Serum Concentrations of Chemokine CXCL12 and Its Specific Receptor CXCR4 in Patients with Esophageal Cancer.

Objectives. Recent investigations have suggested that upregulated levels of inflammatory biomarkers, such as chemokines, may be associated with development of many malignancies, including esophageal cancer (EC). Based on our knowledge, this study is the first to assess the serum concentration of chemokine CXCL12 and its specific receptor CXCR4 in the diagnosis of EC patients. Material and Methods. The present study included 79 subjects: 49 patients with EC and 30 healthy volunteers. The serum concentrations of CXCL12 and CXCR4 and classical tumor markers such as carcinoembryonal antigen (CEA) and squamous cell cancer antigen (SCC-Ag) were measured using immunoenzyme assays, while C-reactive protein (CRP) levels were assessed by immunoturbidimetric method. Moreover, diagnostic criteria of all proteins tested and the survival of EC patients were assessed. Results. The serum concentrations of CXCL12 were significantly higher, while those of its receptor CXCR4 were significantly lower in EC patients compared to healthy controls. The diagnostic sensitivity, negative predictive value, and accuracy of CXCR4 were the highest among all analyzed proteins and increased for combined analysis with classical tumor markers and CRP levels. Conclusion. Our findings suggest that serum CXCR4 may improve the diagnosis of EC patients, especially in combination with classical tumor markers.

The role of selected chemokines and their specific receptors in pancreatic cancer

Pancreatic carcinoma is a highly malignant disease associated with an extremely poor prognosis, which is caused by late presentation, aggressive invasion and metastases, as well as the detection of pancreatic carcinoma in its advanced stages. Thus, better understanding of the tumour biology of this malignancy is sorely needed to improve the clinical outcome. A great challenge for the medical practice is finding a new biomarker of pancreatic carcinoma that will be helpful in diagnosis, in prognosis and in making clinical decisions, including the assessment of patients’ response to therapy. It is suggested that selected chemokines and their specific receptors play an important role in tumour progression, such as tumour growth, angiogenesis, proliferation and development of metastasis. In the present review, general characteristics of chemokines and their specific receptors as well as the significance of these molecules in tumour development are described. The crucial issue of this review is to summarise the importance of various chemokines and their specific receptors in pancreatic carcinoma. Understanding the role of chemokines in the pathogenesis of pancreatic carcinoma is extremely important since these proteins may be used as a potential tool in the diagnosis and prognosis of pancreatic carcinoma patients.

Matrix Metalloproteinases and Their Tissue Inhibitors in Comparison to Other Inflammatory Proteins in Gastric Cancer (GC)

ABSTRACT Gastric cancer (GC) remains a major cause of cancer-related deaths worldwide. The lack of management strategies for the diagnosis of GC in patients gives rise to the challenging questions about the new tumor markers for GC. Developing malignant process may induce local and systemic inflammatory responses. Cancer-associated inflammation is characterized by the infiltration of immune cells. Thus, the inflammation-related proteins, such as cytokines, chemokines, and selected matrix metalloproteinases, may facilitate the growth, proliferation, and migration of tumor cells, including GC. Based on our previous findings, we assessed the significance of various inflammatory mediators as candidates for tumor markers of GC.

Serum chemokine CXCL-8 as a better biomarker for diagnosis and prediction of pancreatic cancer than its specific receptor CXCR-2, CRP and classical tumor markers (CA 19-9 and CEA)

Introduction Novel biomarkers are critically needed to improve the management of patients with pancreatic cancer (PC). Objectives We aimed to evaluate the clinical usefulness of serum CXCL8 in relation to its specific receptor CXCR2 in the diagnosis and prediction of PC compared with classic tumor markers (carbohydrate antigen 19-9 [CA 19-9] and carcinoembryonic antigen [CEA]) and C-reactive protein (CRP). Patients and methods The study included 76 subjects: 42 patients with PC and 34 healthy volunteers. Serum protein levels were measured by immunological methods. Results Serum CXCL8 and CXCR2 concentrations were significantly higher in PC patients compared with healthy controls, similarly to classic tumor markers and CRP. CXCL8 levels were significantly elevated in patients with lymph node metastasis compared with individuals without nodal involvement. The diagnostic sensitivity, accuracy, negative predictive value, and areas under the receiver operating characteristic curves for CXCL8 were higher than those for CXCR2, CRP, CA 19-9, and CEA. Moreover, serum CXCL8 was the only significant predictor of PC risk. Conclusions Our findings indicate the significance of the CXCL8-CXCR2 axis in the pathogenesis of PC. Serum CXCL8 is emerging as the strongest candidate for a potential PC biomarker among all proteins tested.

Stem cell factor in the serum of patients with esophageal cancer in relation to its histological types

Introduction Hematopoietic growth factors (HGFs), such as stem cell factor (SCF), may stimulate proliferation and differentiation of hematopoietic progenitor cells. Stem cell factor is also able to affect the growth of malignant tumors, including esophageal cancer (EC). The prognosis of EC patients’ survival is still unfavorable. Thus, novel biomarkers are necessary to improve the diagnosis and prognosis of EC patients. The aim of this study was to determine the serum SCF concentrations in EC patients in relation to its histological types and compare these levels with the classical tumor marker – carcinoembryonic antigen (CEA). Material and methods The study included 56 EC patients and 65 healthy controls. Serum SCF and CEA concentrations were measured using immunoenzyme assays. Moreover, diagnostic criteria of both proteins tested and the survival of EC patients were assessed. Results The serum SCF concentrations were lower in EC patients compared to healthy controls, but the difference was not significant, whereas CEA levels were higher in EC patients than in healthy subjects. The serum SCF concentrations were significantly higher in patients with adenocarcinoma of the esophagus (AC) than in patients with esophageal squamous cell carcinoma (ESCC). Moreover, the diagnostic sensitivity of SCF (88%) was higher than for CEA (29%) and increased for combined analysis of SCF with CEA. Conclusions Our findings suggest the potential role of serum SCF in the diagnosis of EC patients, especially in combination with the classical tumor marker. However, due to the non-specific nature of SCF, this issue requires further investigations performed on a larger population of EC patients.