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miR-592, as a potential biomarker, has been linked to several cancers. However, the expression level and prognostic value of miR-592 in CRC have not been elucidated. In this study, we detected the miR-592 expression in CRC serum, tumor tissues, adjacent non-tumor tissues (NATs) and four colorectal cancer cell lines by RT-PCR. Our data proved that miR-592 expression was up-regulated in clinical CRC serum and tissues (P < 0.05). Serum or tissue miR-592 in CRC metastatic patients also maintained a high level, compared to that in non-metastatic CRC patients (P < 0.05). After radical surgery, postoperative serum miR-592 level in CRC patients significantly decreased (P < 0.05). Our clinicopathological analysis revealed that high miR-592 was significant associated with the tumor size (P = 0.008), TNM stage (P = 0.026), distant metastasis (P = 0.004) and preoperative CEA level (P = 0.022), which led to a shorter overall survival rate in CRC patients (P = 0.032). Furthermore, we designed and transfected miR-592 mimics or inhibitors into the corresponding CRC lines, and our experiments in vitro demonstrated that miR-592 could promote cell proliferation, wound healing and invasion ability of CRC cells (P < 0.05), while miR-592 did not influence the CRC cell apoptosis (P > 0.05). All these results suggested that miR-592 functioned as a novel and potential carcinogen-initiated and metastasis-related biomarker in CRC, and down-regulation of miR-592 might be considered as a potentially significant molecular treatment strategy for CRC patients.  相似文献   

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ObjectivesA fragment of cytokeratin 19, CYFRA 21-1, has been reported to be a sensitive tumor marker for non-small cell lung cancer (NSCLC). We describe analytical performance characteristics of a novel CYFRA 21-1 assay and hypothesize that CYFRA 21-1 complements the clinical sensitivity of carcinoembryonic antigen (CEA) and squamous cell carcinoma antigen (SCCa).Design and methodsPerformance characteristics of a CYFRA 21-1 immunochemiluminescent assay included analytical sensitivity, imprecision, linearity, analyte stability, and reference interval determination. Ninety-two pretreatment NSCLC serum samples were tested for CYFRA 21-1, CEA, and SCCa. Sensitivity was determined for each marker individually and in combination, with regard to tumor stage and histology.ResultsThe analytical sensitivity was 0.01 ng/mL. Total imprecision ranged from 4.0 to 6.3% at 4.9 to 28.4 ng/mL, respectively. The assay was linear from 0.9 to 71.4 ng/mL (slope = 0.995, intercept = ? 0.60, r2 = 0.999). CYFRA 21-1 was stable for 48 h at ambient temperature and 14 days at 4 °C. The 97.5th percentile of a reference population was 1.9 ng/mL. Across disease stage, the sensitivities of CYFRA 21-1, CEA, and SCCa were 17–81%, 30–52%, and 24–39%, respectively. CYFRA 21-1 combined with CEA or SCCa increased sensitivity above that of any single marker.ConclusionsAn immunochemiluminescent assay for CYFRA 21-1 had favorable performance characteristics. CYFRA 21-1 was complementary to CEA and SCCa and increased clinical sensitivity in patients with NSCLC.  相似文献   

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ObjectivesCA 15-3 is a widely used tumor marker for breast cancer. We have investigated whether the MUC1 568 A/G polymorphism can influence CA 15-3 levels in healthy women and patients with breast tumors.Design and methodsCA 15-3 was measured in 208 healthy women, in 67 with benign disease, and in 162 women with breast cancer. All subjects were genotyped for the MUC1 568 A/G polymorphism.ResultsSignificant differences were observed between mean CA 15-3 levels of control subjects grouped according to the MUC1 568 genotype (mean ± SD): AA (10.3 ± 3.8), AG (15.9 ± 5.0) and GG (19.0 ± 5.6) U/mL, p < 0.0001. Similar (median) results were observed in women with benign breast disease: AA (10.2), AG (14.2) and GG (16.6) U/mL, p < 0.0001, and those with breast cancer: AA (10.4), AG (17.1) and GG (23.9) U/mL, p < 0.0001.ConclusionsThe MUC1 568 A/G polymorphism strongly influences CA 15-3 levels in healthy women and women with either benign or malignant breast tumors.  相似文献   

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BackgroundMatrix metalloproteinases (MMPs) are involved in cardiac remodeling and are encoded by genes showing genetic polymorphisms that have functional implications. We examined whether MMP-9 genetic polymorphisms are associated with hypertension and with left ventricular (LV) remodeling in hypertensive patients.MethodsWe studied 173 hypertensive patients and 137 age, race and gender matched healthy controls. Heart echocardiography was performed in all patients and the following MMP-9 genetic polymorphisms were analyzed: C? 1562T (rs3918242), ? 90 (CA)14–24 (rs2234681) and Q279R (rs17576). Haplo.stats analysis was used to assess whether MMP-9 haplotypes are associated with hypertension. Linear regression analysis was performed to assess whether MMP-9 haplotypes affect LV mass index (LVMI) and other echocardiography parameters.ResultsMMP-9 ? 90 (CA)14–24 “HH” genotype (H allele defined by number of CA repeats ≥ 21) was associated with hypertension (P = 0.0085; OR = 2.321, 95% confidence interval = 1.250 to 4.309). While one MMP-9 haplotype (“C, H, Q”) protects against LVMI and end-diastolic diameter increases due to remodeling (P = 0.0490 and P = 0.0367), another MMP-9 haplotype apparently has detrimental effects over both parameters in hypertensive patients (“T, H, Q”, P = 0.0015 and P = 0.0057, respectively).ConclusionGenetic polymorphisms in MMP-9 gene may modify the susceptibility of hypertensive patients to LV remodeling. Further studies are necessary to examine whether these polymorphisms affect clinical events in hypertensive patients.  相似文献   

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ObjectivesTo evaluate the potential clinical significance of serum autotaxin (ATX) level in patients with cancers of the digestive system.Design and methodsSerum ATX activity was measured as the lysophospholipase D activity in patients with cancer of the esophagus (n = 8), stomach (n = 18), colorectum (n = 21), biliary tract (n = 19), or pancreas (n = 103) and in patients with benign pancreatic diseases (n = 73).ResultsAmong patients with various cancers of digestive system, increased serum ATX activity was predominantly observed among pancreatic cancer patients. Serum ATX activity was not increased in patients with chronic pancreatitis or pancreatic cysts. In the diagnosis of pancreatic cancer, the area under the receiver operating curve for serum ATX activity was 0.541 (95% CI, 0.435–0.648) for men and 0.772 (95% CI, 0.659–0.885) for women. No significant correlation was observed between serum ATX activity and CEA, CA19-9 or Dupan2 levels.ConclusionSerum ATX activity may be useful for identifying pancreatic cancer when used together with other serum markers of pancreatic cancer.  相似文献   

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BackgroundAbnormal production of matrix metalloproteinases (MMPs), especially MMP-9, may play a role in hypertensive disorders of pregnancy. These alterations may result from functional genetic polymorphisms in the promoter region of MMP-9 gene, which are known to change MMP-9 expression. We examined whether 2 MMP-9 polymorphisms (C? 1562 T and (CA)n) and haplotypes are associated with preeclampsia and/or gestational hypertension.MethodsWe studied 476 pregnant women: 176 healthy pregnant (HP), 146 pregnant with gestational hypertension (GH), and 154 pregnant with preeclampsia (PE). Genomic DNA was extracted from whole blood and genotypes for C? 1562 T and (CA)n polymorphisms were determined by PCR-RFLP. Haplotype frequencies were inferred using the PHASE ver. 2.1 program.ResultsFor the g.?90(CA)13–25 polymorphism, no significant differences were found in genotype and allele distributions when PE or GH groups were compared with HP group. However, the CT genotype and T allele for g.?1562C > T polymorphism were more commonly found in GH subjects compared with the HP group (both P < 0.05). Conversely, we found no differences in genotypes or allele distributions for the g.?1562C > T polymorphism when the PE and the HP groups were compared. No significant differences were found in overall distributions of haplotype frequencies when the GH or the PE group was compared with the HP group.ConclusionsThe C? 1562 T polymorphism in MMP-9 gene is associated with gestational hypertension, but not with preeclampsia. These findings may help to explain the higher plasma MMP-9 levels previously reported in GH compared with HP.  相似文献   

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BackgroundCarcinoembryonic antigen (CEA), a serological marker of malignant tumors, demonstrates a modest increase under nonmalignant conditions and the pro-inflammatory features of CEA suggest that CEA may be related to insulin resistance and metabolic syndrome.MethodsA total of 7075 female Korean non-smokers who underwent health check-ups were analyzed in the present study. The interquartile cutoff values for serum CEA concentrations were 0.39, 0.84, and 1.40 ng/ml.ResultsThe prevalence of metabolic syndrome increased significantly with the increasing CEA quartiles, and the age-adjusted mean CEA concentration increased consistently with each additional component of metabolic syndrome. Logistic regression analysis adjusted for age, alcohol intake, exercise, body mass index, total cholesterol, WBC count, and hsCRP showed that the third and fourth CEA quartiles were associated with metabolic syndrome with odds ratios of 1.29 (95% CI 1.07 to 1.63 P < 0.001) and 1.39 (95% CI 1.10 to 1.66, P < 0.001), respectively.ConclusionIn female Korean non-smokers, serum CEA was independently associated with metabolic syndrome. The pathophysiologic and clinical significance of these findings requires further investigation.  相似文献   

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AimGrowing evidence suggest that the microRNA (miR)-23a/24-2/27a cluster may play a crucial role in mammary tumorigenesis and act as a novel class of oncogenes. Among these members, miR-27a has been reported to promote proliferation, migration and invasion in human osteosarcoma cells. The aim of this study was to detect the serum levels of miR-27a in osteosarcoma patients and to investigate its associations with clinicopathological features and prognosis.MethodsmiR-27a levels in sera from 166 osteosarcoma patients and 60 healthy controls were detected by real-time quantitative RT-PCR. Then, the associations of serum miR-27a level with clinicopathological factors or survival of osteosarcoma patients were further evaluated.ResultsCompared to healthy controls, the serum levels of miR-27a were significantly increased in osteosarcoma patients (P < 0.001). Importantly, miR-27a could efficiently screen osteosarcoma patients from healthy controls (Area under receiver operating characteristic curve, AUC = 0.867). Then, high miR-27a expression was more frequently occurred in osteosarcoma patients with advanced clinical stage (P = 0.001), positive distant metastasis (P = 0.01) and poor response to chemotherapy (P = 0.008). In Kaplan–Meier survival analysis, high miR-27a expression was a significant indicator for poor overall survival (P = 0.006) as well as poor disease-free survival (P = 0.01). Furthermore, multivariate analysis demonstrated that miR-27a expression was an independent and significant prognostic factor to predict overall survival (P = 0.01) and disease-free survival (P = 0.03).ConclusionmiR-27a expression may be elevated in sera of osteosarcoma patients and in turn contributes to aggressive progression of this malignancy. Detection of serum miR-27a levels may have clinical potentials as a non-invasive diagnostic/prognostic biomarker for osteosarcoma patients.  相似文献   

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《Journal of critical care》2016,31(6):1190-1194
PurposePatients receiving extracorporeal membrane oxygenation (ECMO) are at risk for thrombocytopenia including heparin-induced thrombocytopenia (HIT). The purpose of this study was to determine the frequency of suspected HIT in patients receiving ECMO and unfractionated heparin (UFH).Materials and methodsWe conducted a retrospective review in adult patients on ECMO. Patients were included if they received ECMO for at least 5 days and concomitant UFH.ResultsThere were 119 patients who met inclusion criteria. Twenty-three patients (19%) had a heparin–platelet factor 4 immunoassay performed. Patients with suspected HIT had a significantly lower platelet count within the first 3 days of ECMO, 69 × 109/L (22-126 × 109/L) vs 87.5 × 109/L (63-149 × 109/L); P = .04. The lowest platelet count on the day of HIT testing was 43 × 109/L (26-73), representing a 71% reduction from baseline. Twenty patients (87%) had an optical density score less than 0.4, and all patients had a score less than 1.0. A functional assay was performed in 7 patients (30%), with only 1 patient having laboratory-confirmed HIT.ConclusionsThe evaluation of HIT occurred in a small percentage of patients, with HIT rarely being detected. Patients who had heparin–platelet factor 4 immunoassay testing exhibited lower platelet counts with a similar duration of ECMO and UFH exposure.  相似文献   

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BackgroundEmergency department (ED) crowding and prolonged waiting times have been associated with adverse consequences towards quality and patient safety.ObjectiveThis study investigates whether the number of patients simultaneously present at the ED might be an indicator of unsafe waiting and at what threshold hospital-wide measures to improve patient outflow could be justified.MethodsData were retrospectively collected during a 1-year period; all ED patients aged ⩾16 years, and triaged as ESI-1 or ESI-2 were eligible for inclusion. The number of patients simultaneously present was used as occupancy rate. Waiting time was considered unsafe if it was longer than 10 min for ESI-1 patients, or longer than 30 min for ESI-2 patients. Differences in waiting time and occupancy between patients with safe and unsafe waiting times were analysed using the Mann–Whitney U test. The ability of the occupancy rate to discriminate unsafe waiting times was analysed using a receiver operating characteristic curve.ResultsThe overall median waiting time was 5 min (IQR = 4–8) for ESI-1, and 12 min (IQR = 6–24) for ESI-2 patients. Unsafe waiting times occurred in 16.0% of ESI-1 patients (median waiting time = 17 min, IQR = 13–23), and in 18.9% of ESI-2 patients (median waiting time = 48 min, IQR = 37–68). The occupancy rate was a weak indicator for unsafe waiting times in ESI-1 patients (AUC = 0.625, 95%CI 0.537–0.713) but a fair indicator for unsafe waiting times in ESI-2 patients (AUC = 0.740, 95%CI 0.727–0.753) for which the threshold to predict unsafe waiting times with 90% sensitivity was 51 patients.ConclusionThe number of patients simultaneously present is a moderate indicator of unsafe waiting times. Future initiatives to improve safe waiting times should not focus solely on occupancy, and expand their focus towards other factors affecting waiting time.  相似文献   

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ObjectivesTo evaluate the diagnostic value of serum osteocalcin in the detection of bone metastases from differentiated thyroid carcinoma (DTC).Design and methodsSerum samples from DTC patients with (DTC BM+, n = 19) or without bone metastases (DTC BM?, n = 19), and matched healthy volunteers (n = 30) were tested for serum osteocalcin with electrochemiluminescent immunoassay.ResultsOsteocalcin was higher in DTC BM+ than in DTC BM? patients (+ 35.8%, p = 0.002), acting as an independent risk factor for bone metastases (R2 = 0.142, p = 0.039). The sensitivity was 78.9% and the specificity was 63.2% at a cut-off value of 11.2 μg/L.ConclusionsSerial measurements of osteocalcin could be useful in the detection of bone metastases from DTC.  相似文献   

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IntroductionMost patients with cardiac arrest (CA) admitted to hospitals after successful cardiopulmonary resuscitation (CPR) are discharged with various degree of neurological deficits. To determine predictor of neurological outcome early and accurately, and to determine cutoff values, serum levels of protein S-100B and neuron-specific enolase (NSE) within 24 h after CA were assessed.Methods and resultsA multicenter prospective observational study was conducted between May 2007 and April 2008 at three medical institutions in Japan on 107 consecutive non-traumatic CA patients with return of spontaneous circulation after CPR. Based on “best-ever achieved” Glasgow-Pittsburgh cerebral performance categories (CPC) score within 6 months after CA, patients were classified into a “poor neurological outcome” group (CPC3 to CPC5) (n = 67) and “favorable neurological outcome” group (CPC1 and CPC2) (n = 13). Blood was sampled on admission, at 6 and 24 h after CA. Serum S-100B and NSE in “poor outcome” group were higher than those in “favorable outcome” group (P < 0.01). On ROC analysis, area under the curve of S-100B was 0.85, 0.94 and 1.0, respectively. These were greater than those of NSE at all sampling points. The “100%-specific” cutoff values of S-100B predictive of poor neurological outcome were 1.41, 0.21, and 0.05 ng/mL, respectively. These values corresponded to sensitivities of 20.9%, 62.8%, and 100%, respectively, each of which was higher than those of NSE.ConclusionsS-100B is more reliable as an early predictor of poor neurological outcome within 24 h after CA than NSE and can be applied clinically.  相似文献   

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ContextBenzodiazepines (BZDs) are commonly prescribed for relief of dyspnea in palliative care, yet few data describe their efficacy.ObjectivesTo describe the management of moderate-to-severe dyspnea in palliative care patients.MethodsChart review of inpatients with moderate or severe dyspnea on initial evaluation by a palliative care service. We recorded dyspnea scores at follow-up (24 hours later) and use of BZDs and opioids.ResultsThe records of 115 patients were reviewed. The mean age of patients was 64 years and primary diagnoses included cancer (64%, n = 73), heart failure (8%, n = 9), and chronic obstructive pulmonary disease (5%, n = 6). At initial assessment, 73% (n = 84) of the patients had moderate and 27% (n = 31) had severe dyspnea. At follow-up, 74% (n = 85) of patients reported an improvement in their dyspnea, of which 42% (n = 36) had received opioids alone, 37% (n = 31) had BZDs concurrent with opioids, 2% (n = 2) had BZDs alone, and 19% (n = 16) had received neither opioids nor BZDs. Logistic regression analysis identified that patients who received BZDs and opioids had increased odds of improved dyspnea (odds ratio 5.5, 95% CI 1.4, 21.3) compared with those receiving no medications.ConclusionMost patients reported improvement in dyspnea at 24 hours after palliative care service consultation. Consistent with existing evidence, most patients with dyspnea received opioids but only the combination of opioids and BZDs was independently associated with improvement in dyspnea. Further research on the role of BZDs alone and in combination with opioids may lead to better treatments for this distressing symptom.  相似文献   

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ObjectivesThe practical application of elevated carbohydrate antigen 125 (CA125) to predict clinical outcome in chronic heart failure (CHF) is under debate. The mechanism for this CA125 elevation remains unknown. We hypothesize that mechanical stress on mesothelial cells initiates CA125 synthesis.Design and methodsA total of 191 patients suffering from edema and/or dyspnea were enrolled. 109 patients were diagnosed as CHF, and 82 patients without CHF were assigned as control group. Echocardiography, CA125, N-terminal pro-brain natriuretic peptide (NT-proBNP), and other biochemical parameters were measured. All enrolled patients underwent heart function classification.ResultsPatients with serous cavity effusion (SCE) demonstrated higher serum CA125 than patients without SCE (82.91 (61.90–103.92) vs. 44.98 (29.66–60.30) U/mL, P < 0.001). In the absence of SCE, CA125 levels in CHF patients were slightly higher than non-CHF patients (52.37 (34.85–69.90) vs. 35.15 (23.81–46.49) U/mL, P = 0.017). Additionally, compared with non-CHF patients, CHF patients had higher levels of high-sensitivity C-reactive protein (hsCRP) and lower superoxide dismutase (SOD). In all enrolled patients, CA125 levels were negatively correlated with SOD concentrations (r = ? 0.567, P < 0.001), and positively correlated with hsCRP levels (r = 0.608, P < 0.001). Receiver operating characteristic curve analysis showed that CA125 was better in predicting SCE than NT-proBNP, while NT-proBNP was more suitable for predicting CHF than CA125. The in vitro study demonstrated that MUC16, the CA125 coding gene, was up-regulated by mechanical stretch on human mesothelial cell line (MeT-5A).ConclusionsCA125 elevation in CHF was associated with SCE. Mechanical extension of mesothelial cells from SCE plays an important role in CA125 increase.  相似文献   

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AimThe prediction of return of spontaneous circulation (ROSC) during resuscitation of patients suffering of cardiac arrest (CA) is particularly challenging. Regional cerebral oxygen saturation (rSO2) monitoring through near-infrared spectrometry is feasible during CA and could provide guidance during resuscitation.MethodsWe conducted a systematic review and meta-analysis on the value of rSO2 in predicting ROSC both after in-hospital (IH) or out-of-hospital (OH) CA. Our search included MEDLINE (PubMed) and EMBASE, from inception until April 4th, 2015. We included studies reporting values of rSO2 at the beginning of and/or during resuscitation, according to the achievement of ROSC.ResultsA total of nine studies with 315 patients (119 achieving ROSC, 37.7%) were included in the meta-analysis. The majority of those patients had an OHCA (n = 225, 71.5%; IHCA: n = 90, 28.5%). There was a significant association between higher values of rSO2 and ROSC, both in the overall calculation (standardized mean difference, SMD –1.03; 95%CI –1.39,–0.67; p < 0.001), and in the subgroups analyses (rSO2 at the beginning of resuscitation: SMD –0.79; 95%CI –1.29,–0.30; p = 0.002; averaged rSO2 value during resuscitation: SMD –1.28; 95%CI –1.74,–0.83; p < 0.001).ConclusionsHigher initial and average regional cerebral oxygen saturation values are both associated with greater chances of achieving ROSC in patients suffering of CA. A note of caution should be made in interpreting these results due to the small number of patients and the heterogeneity in study design: larger studies are needed to clinically validate cut-offs for guiding cardiopulmonary resuscitation.  相似文献   

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BackgroundThe clinical symptoms and pathophysiologic mechanisms during and after ischaemia–reperfusion following cardiac arrest (CA) and successful cardiopulmonary resuscitation (CPR) closely resemble those observed in patients with severe sepsis. Impairment of microcirculation and endothelial leakage seem to play key roles in the underlying pathophysiology. Recombinant human activated protein C (rhAPC) is the first drug being licensed for the treatment of severe sepsis in patients. Therefore, for the first time, we investigated effects of rhAPC on microhaemodynamic changes and endothelial leakage applying in vivo microscopy of postcapillary mesenteric venules after CA and CPR in rats.MethodsAfter 6 min of CA, male Wistar rats were randomised into two groups (n = 10) to receive rhAPC or placebo (0.9% NaCl). Sham-operated animals (n = 10) served as non-ischaemic controls. At 360, 420, and 480 min after CA in vivo microscopy was performed to assess wall shear rate (WSR) and plasma extravasation (PE).ResultsBoth treatment groups showed typical signs of impaired microcirculation and a severe endothelial leakage after CA at all time points studied when compared to the sham group. However, no significant differences between the treatment groups were observed with regard to WSR and PE.ConclusionOur results show that CA with consecutive successful CPR leads to a microcirculatory impairment closely resembling experimentally induced sepsis. Intriguingly, despite these similarities, rhAPC had no significant effects on WSR and PE. Our results strongly suggest that further mechanisms such as mast cell activation might play an important role and have therefore to be studied to elucidate the pathophysiology of “postresuscitation disease”.  相似文献   

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BackgroundNeural precursor cell-expressed, developmentally down regulated 9 (NEDD9), a member of Crk-associated substrate (CAS) family, is highly expressed in multiple cancer types and involved in cancer cell adhesion, migration and invasion. The prognostic value of NEDD9 has been evaluated before and its expression is a predictor of poor prognosis in cancer patients. The objective of this study was to determine the clinical significance of the serum levels of NEDD9 in gastric cancer (GC) patients.Patients and methodsA total of 68 patients with a pathologically confirmed diagnosis of GC were enrolled into this study. Serum NEDD9 concentrations were determined by the solid-phase sandwich (ELISA) method. Twenty-eight healthy age- and sex-matched controls were included into the analysis.ResultsThe median age at diagnosis was 60 years, range 21 to 84 years. Forty-nine (72%) patients were male and cardia was the most common tumor localization (n = 37, 77%) in GC patients. The most frequent histologic subtype was adenocarcinoma (n = 45, 66%). Liver was the most common metastatic site in 32 patients with metastasis (n = 14, 44%). Sixty-one percent of 23 metastatic patients who received palliative chemotherapy (CTx) were CTx-responsive. The median follow-up time was 8 months (range 1 to 23 months). At the end of the observation period, 17 patients (25%) experienced disease progression and 28 of the remaining patients (41%) died. Median progression-free survival (PFS) and overall survival (OS) of the whole group were 4.0 ± 0.7 months [95% confidence interval (CI) = 3–5 months] and 14.6 ± 1.2 months (95% CI = 12–17 months), respectively. One-year and 2-year OS rates were 54.4% (95% CI = 41.3–67.5) and 51.2% (95% CI = 37.3–65.1), respectively. The median serum NEDD9 levels of GC patients were significantly higher than controls (1339.51 vs. 1187.91 pg/mL, P = 0.02). There was no significant difference according to known disease-related clinicopathological or laboratory parameters (P > 0.05). Serum NEDD9 levels had a significant impact on PFS (P = 0.04). On the other hand, serum NEDD9 levels showed no significantly adverse effect on OS (P = 0.50).ConclusionSerum NEDD9 level may be a diagnostic marker for GC patients. Moreover, our study results showed that it was elevated in GC patients and had an unfavorable prognostic effect. However, it has no predictive role on CTx response.  相似文献   

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