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Background: To explore the association between serum human epidermal growth factor receptor 2 (HER 2) extracellular domain (ECD) levels and tissue HER 2 status in metastatic gastric cancer. Patients and Methods: HER 2 status was retrospectively analyzed in 219 advanced gastric or gastroesophageal junction (GEJ) patients. Serum HER 2 ECD was measured by chemiluminescent assay and tissue HER 2 was assessed by fluorescent in situ hybridisation (FISH) and immunohistochemistry (IHC) assay. Results: Significant associations were found between serum HER 2 ECD levels and tissue HER 2 status. Twenty-four patients had HER 2 ECD levels >16.35 ng/mL, which has a sensitivity of 51.4% and a specificity of 97.3% to predict tissue HER 2 status. When the cut-off value was increased to 22 ng/mL, then all 12 patients with serum HER 2 ECD levels>22 ng/mL were tissue HER 2 positive, corresponding to a specificity of 100% and a sensitivity of 32.4%. High serum HER 2 ECD levels were strongly associated with the intestinal histological type (Lauren’s classification), liver metastasis, multiple metastasis (>2) and increased LDH levels, but not with overall survival. Conclusions: The high specificity of the serum HER 2 ECD assay in predicting tissue HER 2 status suggests its potential as a surrogate marker of the HER 2 status in gastric cancer. [ABSTRACT FROM AUTHOR]

Background: To investigate the predictive value of chemokine CCL27 for identifying early stage nasopharyngeal carcinoma (NPC) patients within a population seropositive for Epstein-Barr virus (EBV) capsid antigen-specific IgA (VCA-IgA).Methods: CCL27 in plasma samples from 104 NPC patients, 112 VCA-IgA-positive healthy donors, and 140 VCA-IgA-negative normal subjects was measured by ELISA. Expression of CCL27 in nasopharyngeal tissue from 20 VCA-IgA-positive healthy donors and 20 NPC patients was examined by immunohistochemical staining.Results: Levels of CCL27 in the plasma of VCA-IgA-positive healthy donors (607.33 ± 218.81 pg/ml) were significantly higher than the levels in all NPC patients (437.09 ± 217.74, P = < 0.0001) and in the subset of patients with early stage NPC (463.85 ± 226.17, P = 0.0126). Plasma CCL27 levels were significantly lower in the VCA-IgA-negative normal subjects (358.22 ± 133.15 pg/ml) than in either the VCA-IgA-positive healthy donors (P < 0.0001) or the NPC patients (P = 0.0113). CCL27 protein was detected in 16 of 20 (80%) nasopharyngeal tissue samples from VCA-IgA-positive healthy donors and in 3 of 20 (15%) tumor tissue samples from NPC patients. There was no relationship between CCL27 levels and VCA-IgA titers or plasma EBV DNA content. Receiver operating characteristic (ROC) curves demonstrated that plasma CCL27 levels had a sensitivity of 67.00%, a specificity of 73.10%, and an area under the ROC of 0.725 (95% confidence interval [CI]: 0.657-0.793) for distinguishing between NPC patients and VCA-IgA-positive healthy donors. Further analysis showed that CCL27 levels could distinguish between early stage NPC patients and VCA-IgA-positive healthy donors with an area under the ROC of 0.712 (95% CI: 0.560-0.865), a sensitivity of 59.80%, and a specificity of 84.60%.Conclusions: Chemokine CCL27 could successfully identify NPC patients within a VCA-IgA-positive population. [ABSTRACT FROM AUTHOR]

Background. The pretreatment albumin and globulin ratio (AGR) was an inflammation-associated factor which was related to the overall survival in various malignancies. The aim of this study was to evaluate the prognostic value of AGR in patients with gastric cancer. Method. This retrospective study included 862 cases pathologically diagnosed with gastric cancer. All patients were randomly divided into the testing group (431 cases) and validation group (431 cases). The relationships of AGR with clinicopathologic characteristics and prognosis were analyzed by Kaplan-Meier and Cox regression methods. Results. In the testing group, the median overall survival was 26.90 months and the cutoff value of AGR was 1.50 based on R language. Kaplan-Meier analysis showed that lower AGR was correlated with poorer overall survival. Multivariate analysis demonstrated that AGR was an independent prognostic factor for overall survival (HR: 0.584, 95% CI = 0.351–0.973, and p = 0.039). In the validation group, the median overall survival was 24.10 months. Lower AGR (≤1.50) also had a significantly poorer overall survival by Kaplan-Meier analysis. According to multivariate analysis, the AGR was also confirmed to be an independent prognostic factor for overall survival (HR: 0.578, 95% CI = 0.373–0.897, and p = 0.015). Conclusions. Our study suggested that the pretreatment AGR could be a prognostic biomarker for overall survival in patients with gastric cancer. [ABSTRACT FROM AUTHOR]

Background: Increase of Serum amyloid A (SAA) level has been observed in patients with a variety of cancers. The objective of this study was to determined whether SAA level could be used as a prognostic parameter in patients with esophageal squamous cell carcinoma (ESCC).Methods: SAA levels were measured by rate nephelometry immunoassay in 167 healthy controls and 167 ESCC patients prior to surgical resection. Statistical associations between clinicopathological observations and SAA levels were determined using the Mann–Whitney U test. The clinical value of SAA level as a prognostic parameter was evaluated using the Cox’s proportional hazards model.Results: SAA levels were significantly higher in patients with ESCC compared to levels in healthy controls(13.88 ± 15.19 mg/L vs. 2.26 ± 1.66 mg/L, P < 0.001). Elevation of SAA levels (≥ 8.0 mg/L) was observed in 54.5%(91/167) of patients with ESCC but not in healthy controls. SAA levels were associated with tumor size (P < 0.001),histological differentiation (P = 0.015), T classification (P < 0.001), clinical stage (P < 0.001), lymph node metastasis(P < 0.001) and distant metastasis (P < 0.001), but not with the age and gender of the patients or tumor location.Multivariate analysis revealed that patients with an elevated level of SAA (≥ 8.0 mg/L) had significantly lower 5-year survival rate than those with non-elevated SAA (< 8.0 mg/L, log-rank P < 0.0001).Conclusions: An elevated level of preoperative SAA was found to associate with tumor progression and poor survival in patients with ESCC. [ABSTRACT FROM AUTHOR]

Background: Methyltransferase-like 3 (METTL3) is a member of the m6A methyltransferase family and acts as an oncogene in cancers. Recent studies suggest that host innate immunity is regulated by the enzymes controlling m6A epitranscriptomic changes. Here, we aim to explore the associations between the levels of METTL3 and CD33+ myeloid-derived suppressor cells (MDSCs) in tumour tissues and the survival of patients with cervical cancer (CC).Methods: Specimens of paraffin embedded tumour from 197 CC patients were collected. The expression levels of METTL3 and CD33 were measured by immunohistochemical (IHC) staining. The clinical associations of the IHC variants were analysed by Pearson's or Spearman's chi-square tests. Overall survival (OS) and disease-free survival (DFS) were estimated by the Kaplan-Meier method and log-rank test. Hazard ratios (HRs) and independent significance were obtained via Cox proportional hazards models for multivariate analyses. METTL3 in CD33+ cells or CC-derived cells was knocked down by METTL3-specific siRNA, and MDSC induction in vitro was performed in a co-culture system in the presence of METTL3-siRNA and METTL3-knockdown-CC-derived cells compared with that of the corresponding controls.Results: We found that tumour tissues displayed increased levels of METTL3 and CD33+ MDSCs compared with tumour-adjacent tissues from the same CC patients. Importantly, METTL3 expression was positively related to the density of CD33+ cells in tumour tissues (P = 0.011). We further found that the direct CD33+CD11b+HLA-DR- MDSC induction and tumour-derived MDSC induction in vitro were decreased in the absence of METTL3. The level of METTL3 in tumour microenvironments was significantly related to advanced tumour stage. The levels of METTL3 and CD33+ MDSCs in tumour tissues were notably associated with reduced DFS or OS. Cox model analysis revealed that the level of METTL3 in tumour cells was an independent factor for patient survival, specifically for DFS (HR = 3.157, P = 0.022) and OS (HR = 3.271, P = 0.012), while the CD33+ MDSC number was an independent predictor for DFS (HR: 3.958, P = 0.031). Interestingly, in patients with advanced-disease stages (II-IV), METTL3 in tumour cells was an independent factor for DFS (HR = 6.725, P = 0.010) and OS (HR = 5.140, P = 0.021), while CD33+ MDSC density was an independent factor for OS (HR = 8.802, P = 0.037).Conclusion: Our findings suggest that CD33+ MDSC expansion is linked to high levels of METTL3 and that METTL3 and CD33+ MDSCs are independent prognostic factors in CC. [ABSTRACT FROM AUTHOR]

Background: Elevated serum YKL-40 levels have been observed in various cancers. We evaluated the diagnostic performance of serum YKL-40 alone or in combination with the CEA, CYFRA21-1 and SCCA tumor markers for patients with esophageal squamous cell carcinoma (ESCC).Methods: YKL-40 was detected in ESCC cell lines and tissues by real-time RT-PCR, Western blotting and ELISA. YKL-40 protein expression was determined in 20 ESCC tumor tissues using immunohistochemistry. Serum YKL-40 was measured by ELISA in 126 healthy donors, 59 patients with benign esophageal diseases and 150 patients with ESCC. Serum CEA, CYFRA21-1 and SCCA were determined by electrochemiluminescence.Results: YKL-40 mRNA and protein were observed in ESCC cancer cell lines, tissues and cell culture media, respectively. YKL-40 expression was observed in 17 of 20 ESCC samples (85%). Serum YKL-40 concentration was significantly elevated in patients with ESCC (Range: 6.95-502.10 ng/ml) compared with patients with benign diseases (Range: 1.21-429.30 ng/ml; P = 0.038) and healthy controls (Range: 2.56-132.26 ng/ml; P < 0.001). ROC curves demonstrated that serum YKL-40 has a sensitivity of 72.70%, a specificity of 84.13% and an AUC of 0.874 for the diagnosis of ESCC, which was superior to CEA (Sen: 8.00%; Spe: 96.80%, AUC = 0.652), CYFRA21-1 (Sen: 40.00%; Spe: 92.06%, AUC = 0.746) and SCCA (Sen: 32.67%; Spe: 94.44%, AUC = 0.789). The YKL-40 and SCCA combination was better for diagnosing ESCC (Sen: 82.00%, Spe: 79.37%, PPV: 82.55 and NPV: 78.74; AUC = 0.917) than the YKL-40 and CEA combination (Sen: 74.00%, Spe: 83.20%, PPV: 84.09 and NPV: 72.73; AUC = 0.877), the YKL-40 and CYFRA21-1 combination (Sen: 82.00%, Spe: 77.78%, PPV: 81.46% and NPV: 78.40%; AUC = 0.897) or the CEA, CYFRA21-1 and SCCA combination (Sen: 56.67%, Spe: 84.80%, PPV: 81.73 and NPV: 61.99; AUC = 0.831). Associations between serum YKL-40 levels and the clinic characteristics of ESCC were not significant, with the exception of age (p = 0.001).Conclusions: ESCC tumor cells and tissues express YKL-40. Serum YKL-40 may be a potential biomarker for ESCC. Serum YKL-40 in combination with SCCA significantly increases the sensitivity of detecting ESCC. [ABSTRACT FROM AUTHOR]