Can serum matrix metalloproteinase-9 and SMAD-2 levels predict lamina propria invasion in bladder urothelial carcinoma?

INTRODUCTION: Matrix metalloproteinase-9 (MMP-9) has a role in the destruction of lamina propria (LP) of the bladder wall and SMAD-2 promotes cell-to-cell adhesion. This study aimed to investigate the association between LP invasion and serum protein and mRNA expression levels of MMP-9 and SMAD-2 in bladder cancer (BC) patients. METHODS: Serum samples were taken from 57 patients with suspicious BC before TUR-BT (Group 1) and 20 patients with benign diseases as control (Group 2). The mRNA expression and serum protein levels of MMP-9 and SMAD-2 were analyzed using Real-Time PCR and ELISA methods, respectively. The comparison of protein and mRNA expression levels of MMP-9 and SMAD-2 were done statistically between Group 1 and 2, as well as for different T stages of BC. RESULTS: The protein levels of MMP-9 (2448 vs 637.5 pg/mL, P = .0001) and SMAD-2 (6.85 vs 1.61 P = .0001) were significantly higher in Group 1 compared to Group 2. The mRNA expression levels of MMP-9 (P = .89) and SMAD-2 (P = .99) did not significantly differ between the groups. The protein levels of MMP-9 in T1 patients were significantly higher from both of pTa patients (P = .018) and pT2 (P = .02). The protein levels of SMAD-2 were not statistically different between T stages. Similarly, the mRNA expression levels of MMP-9 and SMAD-2 were not different between T stages. CONCLUSIONS: The protein levels of MMP-9 and SMAD-2 were increased in BC patients while mRNA expressions were not different. Furthermore, the increased protein level of MMP-9 in T1 patients was more pronounced which may be related to LP invasion of the tumor.

Circulating interleukin-18 (IL-18) is a predictor of response to gemcitabine based chemotherapy in patients with pancreatic adenocarcinoma.

BACKGROUND: This study was conducted to investigate the serum levels of interleukin-18 (IL-18) in patients with pancreatic adenocarcinoma (PA) and the relationship with tumor progression and known prognostic parameters. METHODS: Thirty-three patients with PA were studied. Serum samples were obtained on first admission before any treatment. Serum IL-18 levels were analyzed using enzyme-linked immunosorbent assay (ELISA). Age- and sex-matched 30 healthy controls were included in the analysis. RESULTS: The median age at diagnosis was 59 years, range 32-84 years; 20 (61%) patients were men and the remaining were women. The median follow-up time was 26.0 weeks (range: 1.0-184.0 weeks). The median overall survival of the whole group was 41.3 ± 8.3 weeks [95% confidence interval (CI) = 25-58 weeks]. The baseline serum IL-18 levels were significantly higher in patients with PA than in the control group (p < 0.001). Serum IL-18 levels were significantly higher in the patients with high erythrocyte sedimentation rate (ESR) and lactate dehydrogenase (LDH) (p = 0.01 and p = 0.05). Moreover, the chemotherapy-(CTx) unresponsive patients had higher serum IL-18 levels compared to CTx-responsive (p = 0.04) subjects. Conversely, serum IL-18 concentration was found to have no prognostic role on survival (p = 0.45). CONCLUSION: Serum levels of IL-18 can be a good diagnostic and predictive marker; especially for predicting the response to gemcitabine based CTx in patients with PA but it has no prognostic role.

Clinical significance of serum interleukin-29, interleukin-32, and tumor necrosis factor alpha levels in patients with gastric cancer.

Many studies suggested that cytokines interleukin (IL)-29, IL-32, and tumor necrosis factor alpha (TNF-α) are implicated in the pathogenesis of malignancies. The purpose of this study was to determine the clinical significance of the serum levels of IL-29, IL-32, and TNF-α in gastric cancer (GC) patients. Fifty-eight GC patients and 20 age- and sex-matched healthy controls were enrolled into this study. The median age at diagnosis was 59.5 years (range 32-82 years). Tumor localization of the majority of the patients was antrum (n = 42, 72.4 %), and tumor histopathology of the majority of the patients was diffuse (n = 43, 74.1 %). The majority of the patients had stage IV disease (n = 41, 70.7 %). Thirty-six (62.1 %) patients had lymph node involvement. The median follow-up time was 66 months (range 1 to 97.2 months). The baseline serum IL-29 concentrations were not different between patients and controls (p = 0.627). The baseline serum IL-32 and TNF-α concentrations of the GC patients were significantly higher (for IL-32, p = 0.014; for TNF-α, p = 0.001). Gender, localization, histopathology, tumor, and lymph node involvement were not found to be correlated with serum IL-29, IL-32, and TNF-α concentrations (p > 0.05). Patients without metastasis (p = 0.01) and patients who responded to chemotherapy (p = 0.04) had higher serum IL-29 concentrations. Patients older than 60 years had higher serum IL-32 (p = 0.002). Serum IL-29, IL-32, and TNF-α levels were not associated with outcome (p = 0.30, p = 0.51, and p = 0.41, respectively). In conclusion, serum levels of IL-32 and TNF-α may be diagnostic markers, and serum IL-29 levels may be associated with good prognosis in patients with GC.

Circulating serum levels of angiopoietin-1 and angiopoietin-2 in nasopharynx and larynx carcinoma patients.

We aimed to determine the serum levels of angiogenic factors, namely angiopoietins, in nasopharyngeal and laryngeal carcinoma patients. We also aimed to seek the relation of these molecules with tumor grade and their utility as diagnostic biomarkers. We evaluated angiopoietin 1 and 2 levels innasopharynx and larynx cancer patients before treatment. Angiopoietin 2 levels were significantly elevated in larynx carcinoma patients and tended to be elevated in nasopharynx cancer patients compared with healthy controls. However, angiopoietin 1 levels were similar in cancer patients and controls. Angiopoietin 1 levels were significantly higher in nasopharyngeal cancer patients with advanced stages compared to earlier stages. On the other hand, angiopoietin 2 levels were similar in advanced and earlier stage cancer patients.

Diagnostic value of serum M30 and M65 in patients with nasopharyngeal carcinoma.

M30 and M65 are circulating fragments of cytokeratin 18 released during apoptotic cell death and regarded as markers of cell death in patients with various tumor types. Our aim was to investigate the clinical and prognostic significance of the serum M30 and M65 concentrations in patients with advanced nasopharyngeal carcinoma. Thirty-two patients with nasopharyngeal cancer and 32 control subjects were investigated. Serum samples were obtained on first admission before any treatment was initiated. Serum M30 and M65 concentrations were measured by quantitative enzyme-linked immunosorbent assay. Median serum M30 (181.5 vs. 45.5 U/L, p < 0.001) and M65 (384.2 vs. 179.1 U/L, p < 0.001) concentrations were significantly higher in patients with advanced nasopharyngeal carcinomas than in controls. receiver operating characteristic (ROC) analysis showed that a cutoff for M30 of 225 U/L had a sensitivity of 62.5% and a specificity of 73.9% (area under the curve (AUC) = 0.592, 95% confidence interval (CI) 35.3-83.2, p = 0.44), while a cutoff for M65 of 423.4 U/L had a sensitivity of 75.1% and a specificity of 65.6% (AUC = 0.562, 95 % CI 36.0-76.5, p = 0.60). However, serum M30 and M65 were not important prognostic factors for progression-free survival. There were no statistically significant correlations between serum M30 and M65 concentrations and clinicodemographical variables. Serum M30 and M65 concentrations were found to have a diagnostic value in nasopharyngeal cancer. However, neither M30 nor M65 serum levels played a prognostic role in the outcome in nasopharyngeal cancer patients.

Clinical significance of serum insulin-like growth factor-1 (IGF-1) and insulinlike growth factor binding protein-3 (IGFBP-3) in patients with epithelial ovarian cancer.

Insulin-like growth factor-1 (IGF-1) and its primary binding protein IGFBP-3 play an important role in cellular proliferation, differentiation, and apoptosis in many tumors, including ovarian cancer. The objective of this study was to determine the clinical significance of the serum levels of IGF-1 and IGFBP-3 in epithelial ovarian cancer (EOC) patients. A total of 50 patients with a pathologically confirmed diagnosis of EOC were enrolled into this study. Serum IGF-1 and IGFBP-3 levels were determined by the solid-phase sandwich ELISA method. Twenty age- and sex-matched healthy controls were included in the analysis. Median age of patients was 56.5 years old (range 22 to 83 years). Majority of the patients had advanced disease (FIGO stage III-IV; 90%). No significant difference was observed in baseline serum IGF-1 and IGFBP-3 levels between EOC patients and healthy controls (p = 0.99 and p = 0.80, respectively). The young patients had higher serum IGF-1 and IGFBP-3 concentrations (p = 0.04 and p = 0.02, respectively). Patients with normal CA-125 levels had higher serum IGFBP-3 concentrations compared with those with higher CA-125 levels (p = 0.008). However, no other clinical variables including histology, tumor grade, stage of disease, and response to chemotherapy were found to be correlated with serum IGF assays (p > 0.05). A trend to significant relationship was found between the serum levels of IGF-1 and IGFBP-3 (r(s) = 0.212, p = 0.07). The patients with elevated serum IGF-1 levels had favorable progression-free and overall survivals than those with lower levels (p = 0.04 and p = 0.03, respectively). However, serum IGFBP-3 concentrations were found to have no prognostic role for both survivals (p = 0.12 and p = 0.26, respectively). In conclusion, elevated serum level of IGF-1 is associated with favorable progression-free and overall survivals in EOC patients.

Clinical significance of serum transforming growth factor-beta 1 (TGF-ß1) levels in patients with epithelial ovarian cancer.

Transforming growth factor-beta 1 (TGF-ß1) plays an important role in the pathogenesis of multiple malignancies, and its expression also strongly affects the outcomes of cancer patients. The objective of this study was to determine the clinical significance of the serum levels of TGF-ß1 in epithelial ovarian cancer (EOC) patients. A total of 50 patients with a pathologically confirmed diagnosis of EOC were enrolled into this study. Serum TGF-ß1 concentrations were determined by the solid-phase sandwich ELISA method. Thirty age- and sex-matched healthy controls were included in the analysis. Median age of patients was 56.5 years old (range 22 to 83 years). Majority of the patients had advanced disease (FIGO stage III-IV; 90%). There was no significant difference in baseline serum TGF-ß1 levels between EOC patients and the controls (p = 0.39). A trend to significant relationship was found between the serum levels of TGF-ß1 and stage of disease (p = 0.06). The elevated serum TGF-ß1 level was associated with metastatic disease. The other known clinical variables including histology, grade of histology, debulking surgery, and serum CA 125 levels were not found to be correlated with serum TGF-ß1 concentrations (p > 0.05). Only the chemotherapy-unresponsive patients had higher serum TGF-ß1 levels compared with responsive ones (p = 0.02). Serum TGF-ß1 concentration was found to have no prognostic role for both progression-free and overall survivals (p = 0.42 and p = 0.09, respectively). In conclusion, although the serum level of TGF-ß1 has no diagnostic and prognostic role, it is associated with sensitivity to standard chemotherapy in EOC patients.

Serum levels of macrophage migration-inhibitory factor (MIF) have diagnostic, predictive and prognostic roles in epithelial ovarian cancer patients.

Macrophage migration-inhibitory factor (MIF) plays an important role in the pathogenesis of multiple malignancies, and its expression strongly also affects outcomes of cancer patients. The objective of this study was to determine the clinical significance of serum levels of MIF in epithelial ovarian cancer (EOC) patients. A total of 50 patients with a pathologically confirmed diagnosis of EOC were enrolled into this study. Serum MIF concentrations were determined using the solid-phase sandwich ELISA method. Age- and sex-matched 30 healthy controls were included in the analysis. Median age of patients was 56.5 years old, range 22 to 83 years. Majority of the patients had an advanced disease (International Federation of Gynecologists and Obstetricians (FIGO) stages III and IV) (90%). Baseline serum MIF levels were significantly higher than those in the healthy control group (p = 0.005). No known clinical variables including histology, grade of histology, stage of disease, debulking surgery, and serum CA 125 levels were found to be correlated with serum MIF levels (p > 0.05). Only those chemotherapy-unresponsive patients had higher serum MIF levels compared with responsive ones (p = 0.02). Patients with elevated serum MIF concentrations had significantly unfavorable overall survival compared to those with lower levels (p = 0.01). However, a serum MIF level was found to play no prognostic role for progression-free survival (p = 0.09). In conclusion, serum levels of MIF have diagnostic, predictive, and prognostic roles in EOC patients.

Clinical significance of serum epithelial cell adhesion molecule (EPCAM) and vascular cell adhesion molecule-1 (VCAM-1) levels in patients with epithelial ovarian cancer.

Cellular adhesion molecules might be good markers in some types of malignant tumors, useful information in diagnosis and prognosis. The objective of this study was to evaluate the serum levels of epithelial cell adhesion molecule (EPCAM) and vascular cell adhesion molecule-1 (VCAM-1) in epithelial ovarian cancer (EOC) patients. Fifty patients were enrolled into the study. Serum EPCAM and VCAM-1 levels were determined by the solid-phase sandwich ELISA method. Age- and sex-matched 30 healthy controls were included in the analysis. The median age of the patients was 56.5 years, range 22 to 83 years. Majority of the patients had advanced disease (stages III-IV) (90%). The baseline serum EPCAM levels of the EOC patients were significantly higher than in those in the control group (p = 0.03). However, there was no significant difference in the serum VCAM-1 level between EOC patients and controls (p = 0.24). Metastatic patients had higher serum VCAM-1 levels compared with the non-metastatic patients (p = 0.03). Moreover, no other clinical variables including response to chemotherapy were found to be correlated with both serum assays (p > 0.05). No correlation was found between serum EPCAM and VCAM-1 levels in EOC patients (r(s) = 0.105, p = 0.362). Neither serum EPCAM level nor serum VCAM-1 level had significant adverse effect on survival. In conclusion, the higher baseline serum levels of VCAM-1 were associated with metastatic disease, and serum EPCAM level was found to be a diagnostic marker in EOC patients. However, both serum assays had no prognostic roles on outcome.

Circulating annexin A2 as a biomarker in patients with pancreatic cancer.

BACKGROUND: Pancreatic cancer (PC) is a highly lethal malignancy. There are only few predictive or prognostic markers for PC. This study was conducted to investigate the serum levels of annexin A2 (AnxA2) in patients with PC and its relationship with tumor progression and known prognostic parameters. MATERIALS AND METHODS: Serum samples were obtained on the first admission before any treatment. Serum AnxA2 levels were determined using enzyme-linked immunosorbent assay. Age- and sex-matched healthy controls were included in the analysis. All statistical tests were carried out using two-sided test, and P ≤ 0.05 was considered statistically significant. RESULTS: The median age at diagnosis was 59 years. The most common metastatic site was liver in 23 patients with metastasis (n = 19, 83%). At the end of the observation period, thirty-two patients (97%) were dead. Thirty-nine percent of 23 metastatic patients who received palliative chemotherapy (CTx) were CTx responsive. Median overall survival of the whole group was 41.3 ± 8.3 weeks (95% confidence interval = 25-58 weeks). The baseline serum AnxA2 levels were significantly higher in patients with PC than in the control group (P = 0.01). Serum AnxA2 levels were significantly higher in the patients with high erythrocyte sedimentation rate (P = 0.04). Conversely, serum AnxA2 concentration had no prognostic role on survival (P = 0.18). CONCLUSIONS: AnxA2 is identified as a novel secretory biomarker for PC, but it has no role as a prognostic or predictive marker.

Detection of serum protein and circulating mRNA of cMET, HGF EGF and EGFR levels in lung cancer patients to guide individualized therapy.

BACKGROUND: Reseptor tyrosine kinases (cMET and EGFR) are important in lung cancer targeted therapy. We believe if we can use them as markers for clinicians to help decide the diagnosis of lung cancer. This parameter will be important in serum samples of patients with lung cancer diagnosis and treatment. The aim of this study is aimed to evaluate the clinical utility of serum protein and circulating mRNA of cMET and HGF in lung cancer patients. We also analyzed the correlation of mRNA expression with clinicopathologic parameters. METHODS: We performed enzyme-linked immunosorbent assay (ELISA) to measure and compare serum protein and circulating mRNA of cMET and HGF levels in peripheral blood from 60 lung cancer patients and 40 healthy control group. RESULTS: We found that both protein and gene expression levels of serum c-MET, HGF and EGFR were significantly higher in patients with lung cancer than control group. There was no association between HGF, cMET, EGF, EGFR (both protein and gene) expression levels with age, gender, smoking habit, COPD, pathological types or tumor size, stage, metastatic-non metastatic adenocarcinoma-squamous carcinoma, SCLC-NSCLC. As a result of ROC analysis, serum cMET (AUC: 0.892) and HGF protein (AUC: 0.784) were diagnosed in lung cancer patients (Fig. 1). The AUC values of serum EGF and EGFR proteins were calculated to be 0.631 and 0.692, respectively. CONCLUSION: To our knowledge this is the first study comparing the levels of protein and mRNA in the serum material of HGF, c-MET, EGF and EGFR parameters in lung cancer patients' blood samples. Further prospective studies with more participants for better understanding of mechanism and effect for HGF and c-MET inhibitors in lung cancer will help us to identify of these biomarkers role for guiding us to sellect individualized itargeted therapies.

The Diagnostic Significance of PDGF, EphA7, CCR5, and CCL5 Levels in Colorectal Cancer.

In this study, we compared the levels of C-C chemokine receptor type 5 (CCR5), C-C motif chemokine ligand 5 (CCL5), platelet-derived growth factor (PDGF), and EphrinA7 (EphA7) in patients with colorectal carcinoma and healthy controls in order to investigate the significance and usability of these potential biomarkers in early diagnosis of colorectal cancer. The study included 70 colorectal carcinoma patients and 40 healthy individuals. The CCR5, CCL5, PDGF, and EphA7 levels were measured using ELISA in blood samples. PDGF-BB, EphA7, CCR5, and CCL5 levels of the patients with colorectal carcinoma were significantly higher compared to the control group (p < 0.001 for each comparison). Our logistic regression analysis (the area under the curve was 0.958) supports the notion that PDGF-BB, EphA7, and CCL5 are potential biomarkers for the diagnosis of colon cancer. The sensitivity, specificity, and positive and negative predictive values were found to be 87.9%, 87.5%, 92.1%, and 81.4%, respectively. To our knowledge, this is the first study that investigates the relationship between colorectal carcinoma and the four biomarkers CCL5, CCR5, PDGF, and EphA7. The significantly elevated levels of all these parameters in the patient group compared to the healthy controls indicate that they can be used for the early diagnosis of colorectal carcinoma.

Diagnostic and Prognostic Significance of Carboxypeptidase A4 (CPA4) in Breast Cancer.

Recent research focused on prolonged survival has suggested that carboxypeptidase A4 (CPA4) plays a role in both tumor microenvironment formation and distant metastasis in cancer. In some patients, serum and expression (mRNA) levels of CPA4 have been found to be correlated with the aggressiveness and progression of the disease. Accordingly, we conducted a first study to investigate the diagnostic and prognostic significance of CPA4 in the case of breast cancer (BC), the most common form of malignancy in women. The study included a total of 50 patients with BC and 20 healthy women as the control group. The participants' serum CPA4 levels were determined by the ELISA test, and, for assessment of CPA4 mRNA, we used the PCR method. The serum CPA4 (p = 0.001) and CPA4 mRNA (p = 0.015) levels were found to be statistically significantly higher in the controls, compared to the patient group. When the results of patient group were statistically analyzed based on subgrouping by tumor characteristics, the measured CPA4 mRNA levels showed significant difference with respect to the molecular subtype (p = 0.006), pN status (p = 0.023), and pathological stage (p = 0.039), while the serum CPA4 measurements differed significantly in terms of pathological type only (p = 0.024). We conclude that CPA4 is diagnostically and prognostically not futile when used in combination with the other considerations and measurements in breast cancer.

Serum nectin-2 and nectin-4 are diagnostic in lung cancer: which is superior?

Nectins are immunoglobulin-like molecules that are involved in cell to cell adhesion by forming tight junctions and homophilic/heterophilic interactions. This study aimed to analyze serum nectin­2 and nectin­4 levels in lung cancer patients and to evaluate the prognostic, diagnostic and predictive strengths. Data from 74 lung cancer patients were retrospectively examined and enzyme-linked immunosorbent assays (ELISA) were used to measure serum nectin­2 and nectin­4 concentrations. A total number of 40 age and sex-adjusted healthy controls were also enrolled in the study. The median serum nectin­2 and nectin­4 levels of the patients were significantly higher than those of controls (p < 0.001); however, neither biomarker was found to be associated with clinicopathological parameters, (p > 0.05), and furthermore they were found not to be correlated with either overall survival or progression-free survival (p > 0.05). Even though both markers showed high diagnostic values, serum nectin­2 was found superior to both serum nectin­4 and serum nectin-2 + nectin­4 combinations in the diagnosis of lung cancer according to higher sensitivity, specificity and predictive values. Serum nectin­2 and nectin­4 might be used in lung cancer diagnosis but the diagnostic importance of nectin­2 is higher. The prognostic and predictive strengths in cancer are controversial. Furthermore, the interactions with tumor microenvironments and the potentials as therapeutic targets for malignancies have yet to be elucidated.

Significance of serum neural precursor cell-expressed developmentally downregulated protein 9 in melanoma.

Neural precursor cell-expressed developmentally downregulated protein 9 (NEDD9) is a promoter for various cellular functions that result in tumorigenesis. The aim of the present study was to analyse the serum levels of NEDD9 in melanoma patients in order to evaluate its prognostic, predictive and diagnostic value. Data from 112 melanoma patients were retrospectively analyzed and ELISA assays were used to measure serum NEDD9 concentration. The median serum NEDD9 levels of the patients were significantly higher compared with those of the controls. Serum NEDD9 was not found to be associated with any of the clinicopathological parameters, and was also not found to be prognostic for survival in melanoma. Therefore, serum NEDD9 may be of diagnostic value in melanoma, but its usefulness in prognosis remains controversial. The important role of NEDD9 in tumor angiogenesis necessitates efforts to elucidate its interactions with the tumor microenvironment and its potential as a therapeutic target for malignancies.

Clinical Significance of Serum NEDD9 Levels in Patients with Pancreatic Cancer.

INTRODUCTION: Pancreatic cancer (PC) is a lethal malignancy. Various diagnostic, predictive, and prognostic biomarkers have been evaluated. This study was conducted to investigate the serum levels of neural precursor cell expressed developmentally downregulated protein 9 (NEDD9) in patients with PC and the relationship between tumor progression and known prognostic parameters. MATERIALS AND METHODS: Serum samples were obtained on first admission before any treatment. Serum NEDD9 levels were determined using enzyme-linked immunosorbent assay (ELISA). Age- and sex-matched healthy controls were included in the analysis. RESULTS: In a three year period, 32 patients with a pathologically-confirmed diagnosis of PC were enrolled in this study. The median age at diagnosis was 61 years, range 38 to 84 years; the majority of the patients in the group were men (n = 20, 62.5%). The tumor was located in the head of pancreas in 21 (65.6%) patients. Forty-one percent of 17 metastatic patients who received palliative CTx (chemotherapy) were CTx-responsive. The baseline serum NEDD9 levels were significantly higher in patients with PA than in the control group (p = 0.03). Median OS of the whole group were 27 ± 7.3 weeks. Alcohol intake, performance status, and LDH levels were found to be significant prognostic factors (p = 0.006, p < 0.001, and p < 0.001, respectively). However, serum NEDD9 levels had no significantly effect on progression free survival (PFS) and overall survival (OS) (p = 0.71 and p = 0.58, respectively). CONCLUSIONS: NEDD9 is identified as a secretory biomarker for PC but it has no prognostic role.

Clinical Significance of Serum Ykl-40 (Chitinase-3-Like-1 Protein) as a Biomarker in Melanoma: an Analysis of 112 Turkish Patients

Background: Angiogenesis plays an essential role in tumor growth and serum levels of YKL-40 , a strong angiogenic factor that promotes tumor vessel development, has been found to be elevated in various cancers. We here investigated correlation between melanoma parameters and serum YKL-40 levels, to assess potential diagnostic, prognostic and predictive values. Material and Methods: Data for 112 pathologically confirmed cutaneous melanomas of any stage were examined retrospectively. ELISA assays were used to measure serum YKL-40 in plasma samples. Results: The baseline serum YKL-40 levels were significantly higher in patients than healthy controls (174.88 vs 120.10 ng/mL, p<0.001). However, values did not correlate with clinicopathological parameters, (p>0.05), and furthermore there was no apparent prognostic influence on melanoma survival (HR: 1.568; 95% CI, 0.580-3.051; p=0.838). Conclusion: Serum YKL-40 can be useful for diagnosis of melanoma, but reliability in assessing prognosis is questionable. We believe that efforts should be made to understand the interaction between YKL-40 and the tumor environment, and establish whether it might be the target for treatment of malignancies.

Elevated circulating monocyte chemoattractant protein 1 (MCP-1/CCL-2) level may be an unfavorable predictive factor to platinum- and taxane-based combination chemotherapy in patients with gastric cancer.

PURPOSE: Monocyte chemoattractant protein 1 (MCP-1/CCL-2) is a member of the CC chemokine family and a potent chemotactic factor for monocytes that regulate migration and infiltration of monocytes and macrophages. It plays an important role in the pathogenesis of multiple malignancies, and its expression strongly also affects the outcomes of cancer patients. The objective of this study was to determine the clinical significance of the serum levels of MCP-1/CCL-2 in gastric cancer patients. MATERIALS AND METHODS: A total of 78 patients diagnosed with gastric cancer were enrolled in this study. Serum MCP-1/CCL-2 concentrations were determined by the solid-phase sandwich ELISA method. Age- and sex-matched 30 healthy controls were included in the analysis. RESULTS: The median age at diagnosis was 60 years, range 21­84 years. The baseline serum MCP-1/CCL-2 concentrations of the gastric cancer patients were significantly higher than of healthy subjects (p < 0.001). The known clinical variables including gender, age, site of lesion, histopathology, tumor size, lymph node involvement, and stage of disease were not found to be correlated with serum MCP-1/CCL-2 concentrations (p > 0.05). However, a significant relationship was shown between serum MCP-1/CCL-2 levels and response to chemotherapy (p = 0.05). Chemotherapy non-responsive patients had higher serum MCP-1/CCL-2 concentrations. Serum MCP-1/CCL-2 concentrations were not associated with prognosis on both progression-free and overall survival (p = 0.53 and p = 0.39, respectively). CONCLUSION: Elevated circulating MCP-1/CCL-2 level may be an unfavorable predictive factor to chemotherapy based on platinum and taxane in patients with gastric cancer. However, serum MCP-1/CCL-2 concentrations were not associated with prognosis on both progression-free and overall survival.

Serum activated leukocyte cell adhesion molecule and intercellular adhesion molecule-1 in patients with gastric cancer: Can they be used as biomarkers?

Cellular adhesion molecules might be used as markers in diagnosis and prognosis in some types of malignant tumors. The purpose of this study was to determine the clinical significance of the serum levels of activated leukocyte cell adhesion molecule-1 (ALCAM) and intercellular adhesion molecule-1 (ICAM-1) in gastric cancer (GC) patients. Fifty-eight GC patients and 20 age- and sex-matched healthy controls were enrolled into this study. Pretreatment serum markers were determined by the solid-phase sandwich enzyme-linked immunosorbent assay (ELISA). The median age at diagnosis was 59.5 years (range 32-82 years). Tumor localizations of the majority of the patients were antrum (n=42, 72.4%) and tumor histopathologies of the majority of the patients were diffuse (n=43, 74.1%). The majority of the patients had stage IV disease (n=41, 70.7%). Thirty six (62.1%) patients had lymph node involvement. The median follow-up time was 66 months (range 1-97.2 months). At the end of the observation period, 26 patients (44.8%) were dead. The median survival for all patients was 21.4±5 months (%95 CI, 11.5-31.3). The 1-year survival rates were 66.2%. The baseline serum ALCAM levels of the patients were significantly higher than those of the controls (p=0.001). There was no significant difference in the serum levels of ICAM-1 between the patients and controls (p=0.232). No significant correlation was detected between the levels of the serum markers and other clinical parameters (p>0.05). Tumor localization (p=0.03), histopathology (p=0.05), and response to chemotherapy (p=0.003) had prognostic factors on survival. Neither serum ALCAM levels nor serum ICAM-1 levels were identified to have a prognostic role on overall survival (ICAM-1 p=0.6, ALCAM p=0.25). In conclusion, serum levels of ALCAM were found to have diagnostic value in GC patients.

Clinical significance of serum omentin-1 levels in patients with pancreatic adenocarcinoma.

BACKGROUND: Omentin is related with metabolic syndrome and obesity. Pancreatic adenocarcinoma (PA) is a lethal and obesity-linked malignancy. This study was conducted to investigate the serum levels of omentin in patients with PA and the relationship with tumor progression and known prognostic parameters. MATERIAL AND METHODS: Serum samples were obtained from thirty-three patients on first admission before any treatment. Age, sex and body mass index (BMI) matched 30 healthy controls were included in the analysis. Both serum omentin levels were measured using enzyme-linked immunosorbent assay (ELISA). RESULTS: The median age at diagnosis was 59 years (32-84 years). Twenty (61%) patients were men and the remaining were women. The most common metastatic site was liver in 23 patients with metastasis (n = 19, 83%). Thirty-nine percent of 23 metastatic patients who received palliative chemotherapy (CTx) were CTx-responsive. Median overall survival of the whole group was 41.3 ± 8.3 weeks [95% confidence interval (CI) = 25-58 weeks]. The baseline serum omentin levels were significantly higher in patients with PA than in the control group (p < 0.001). Serum omentin levels were significantly higher in patients with larger pathologic tumor size compared with smaller size (p = 0.03). Conversely, serum omentin concentration was found to have no prognostic role on survival (p = 0.54). CONCLUSION: Serum levels of omentin may have a good diagnostic role in patients with PA.