Background: The interaction between tumor cells and inflammatory cells has not been systematically investigated in esophageal squamous cell carcinoma (ESCC). The aim of the present study was to evaluate whether preoperative the lymphocyte-monocyte ratio (LMR), the neutrophil-lymphocyte ratio (NLR), and the platelet-lymphocyte ratio (PLR) could predict the prognosis of ESCC patients undergoing esophagectomy. Materials and Methods: Records from 218 patients with histologically diagnosed ESCC who underwent attempted curative surgery from January 2007 to December 2008 were retrospectively reviewed. Besides clinicopathological prognostic factors, we evaluated the prognostic value of the LMR, the NLR, and the PLR using Kaplan-Meier curves and Cox regression models. Results: The median follow-up was 38.6 months (range 3-71 months). The cutoff values of 2.57 for the LMR, 2.60 for the NLR and 244 for the PLR were chosen as optimal to discriminate between survival and death by applying receiver operating curve (ROC) analysis. Kaplan-Meier survival analysis of patients with low preoperative LMR demonstrated a significant worse prognosis for DFS (p=0.004) and OS (p=0.002) than those with high preoperative LMR. The high NLR cohort had lower DFS (p=0.004) and OS (p=0.011). Marginally reduced DFS (p=0.068) and lower OS (p=0.039) were found in the high PLR cohort. On multivariate analysis, only preoperative LMR was an independent prognostic factor for both DFS (p=0.009, HR=1.639, 95% CI 1.129-2.381) and OS (p=0.004, HR=1.759, 95% CI 1.201-2.576) in ESCC patients. Conclusions: Preoperative LMR better predicts cancer survival compared with the cellular components of systemic inflammation in patients with ESCC undergoing esophagectomy.

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Background:Accumulating evidence indicates that dysregulated microRNA-146a (miR-146a) is involved in tumour genesis and cancer progression. We aimed to evaluate its expression level and the potential for the diagnosis and prognosis in oesophageal squamous cell cancer (ESCC).Methods:We examined miR-146a expression in 62 pairs of ESCC cancerous and matched paracancerous tissue, 115 formalin-fixed paraffin-embedded (FFPE) tissue samples and serum samples from 154 ESCC patients and 154 healthy volunteers using quantitative reverse transcription–PCR (qRT–PCR). Kaplan–Meier method, Cox regression and receiver-operating characteristic (ROC) curve analysis were applied to analyse its prognostic and diagnostic value.Results:MicroRNA-146a expression level was significantly decreased in ESCC tissue compared with paracancerous tissue (P<0.001). Its regulation level was negatively associated with T factor and TNM stage. Kaplan–Meier curve revealed that its downregulation level predicted worse overall survival (OS) and progression-free survival (PFS). Both univariate and multivariate analyses identified miR-146a expression as independent prognostic factor for OS and PFS. Serum miR-146a was significantly reduced in ESCC patients than in healthy controls (P<0.001). Area under the curve ROC value, sensitivity and specificity for this marker were 0.863±0.033, 85.7% and 68.6% in the Discovery Group, and 0.891±0.027, 82.1% and 83.3% in the Validation Group.Conclusions:MicroRNA-146a is significantly reduced in cancerous tissue and serum samples of ESCC patients. It is an ideal biomarker for the prognosis and diagnosis of ESCC.

The objective of this study was to investigate the clinical significance of systemic inflammation score (SIS) and prognostic nutritional index (PNI) in esophageal squamous cell carcinoma (ESCC) patients who underwent esophagectomy. Records from 206 patients with histologically diagnosed ESCC who underwent esophagectomy at Qilu Hospital of Shandong University from January 2007 to December 2008 were retrospectively reviewed. The median disease-free survival (DFS) of this cohort was 32.3 months and 5-year DFS was 34.5 %. The median overall survival (OS) was 39.5 months and 5-year OS was 40.8 %. We found that high SIS was significantly associated with increased tumor length (p = 0.021), increased depth of invasion (p = 0.001), lymph node metastasis (p = 0.038), and advanced pathological stage (p = 0.004). Kaplan-Meier survival analysis revealed that both high SIS and low PNI were significantly associated with inferior DFS (for the SIS, p = 0.005; for the PNI, p = 0.003) and OS (for the SIS, p = 0.007; for the PNI, p = 0.002). In multivariate analysis, SIS was an independent prognostic indicator for both DFS and OS. However, PNI was not an independent prognosticator in multivariate analysis. SIS was a novel and promising inflammation-based prognostic score than PNI in ESCC patients who underwent esophagectomy.

We aimed to investigate the pattern of expression and clinical significance of isocitrate dehydrogenase 1(IDH1) in esophageal squamous cell carcinoma (ESCC). The IDH1 expression was determined by quantitative real-time polymerase chain reaction, immunohistochemistry, and Western blot analysis using 38 pairs of frozen tissues. Enzyme-linked immunosorbent assay was employed to measure 67 pairs of serum samples from patients and their controls to evaluate its diagnostic value. Immunohistochemistry analysis of 111 formalin-fixed paraffin embedded tissue samples was conducted for explaining its prognostic value. After shRNA transfection, CCK8 and clonal efficiency assays were carried on for verifying the function of IDH1 in vitro. Increased expression at mRNA (P < 0.001) and protein levels (immunohistochemistry: P < 0.001, Western blot analysis: P < 0.001) were observed. Similarly, the IDH1 expression in serum from patients with ESCC was significantly upregulated relative to that from healthy controls (P < 0.001). Kaplan–Meier curve indicated that IDH1 upregulation predicted worse overall survival (OS) and progression-free survival (PFS). Univariate and multivariate analyses identified IDH1 expression as an independent prognostic factor for OS and PFS. Furthermore, OD450 values and colony numbers were decreased in sh-IDH1 groups (all P < 0.05). In conclusion, IDH1 is upregulated in patients with ESCC and can be used as a good potential biomarker for diagnosis and prognosis.

MicroRNA-613 (miR-613) plays important roles in tumorigenesis and cancer progression. We aimed to evaluate its expression level and potential for diagnosis and prognosis in esophageal squamous cell cancer (ESCC). We examined miR-613 expression in 60 pairs of ESCC cancerous and matched paracancerous tissues, serum samples from 75 ESCC patients and 75 healthy volunteers, and 105 formalin-fixed paraffin-embedded (FFPE) tissue samples using quantitative reverse transcription polymerase chain reaction. Receiver-operating characteristic (ROC) curve analysis, Kaplan-Meier method, and Cox regression were applied to analyze its diagnostic and prognostic value. MiR-613 was significantly decreased in ESCC tissue compared with paracancerous tissue (P < 0.001). Moreover, the expression level of miR-613 was significantly reduced with increased T stage of ESCC. Statistically significant difference between ESCC patients and healthy controls in expression level of miR-613 (0.89 ± 0.73 vs. 1.71 ± 1.03, P < 0.001) was found. The area under the ROC curve (AUC) based on serum miR-613 was 0.767 ± 0.040. We also performed analysis on early-stage patients and revealed that the AUC value was 0.728 ± 0.052 (P < 0.001). The Kaplan-Meier curve revealed that the downregulation of miR-613 was related to worse overall survival (OS) and progression-free survival (PFS) of ESCC patients (P = 0.018 and P = 0.035, respectively). Furthermore, the multivariate analysis identified miR-613 to be an independent prognostic factor for OS and PFS (P = 0.031 and P = 0.006, respectively) In conclusion, miR-613 is significantly reduced in cancerous tissue and serum samples of ESCC patients. It can serve as an ideal indicator for the diagnosis and prognosis of ESCC.

We aimed to examine Notch2 expression in oesophageal squamous cell carcinoma (ESCC) patients and to evaluate its prognostic potential. Immunohistochemical (IHC) staining, quantitative real-time polymerase chain reaction (qRT-PCR) and western blot analysis were utilized to investigate the Notch2 expression status and prognostic value. Furtherly, CCK8 and clonogenic assays were conducted to determine if Notch2 inhibition by shRNA could lead to a decrease in the proliferation and survival of ESCC cells. A notably higher Notch2 expression level was found in ESCC tissues at the mRNA (P < 0.0001) and protein levels (IHC: P = 0.004; western blot: P = 0.021). Log-rank analysis demonstrated that Notch2 overexpression was significantly associated with worse overall survival (OS) (29.1% vs. 49.1%; P = 0.013) and progression-free survival (PFS) (15.3% vs. 34.4%; P = 0.006) rates in ESCC patients. The multivariate analysis revealed Notch2 as an independent prognostic factor for OS and PFS (P = 0.002 and 0.006, resp.). Besides, in vitro assays showed that OD450 values and colony formations were significantly reduced in Notch2-shRNA group (all P < 0.0001). In conclusion, these results show that Notch2 is up-regulated in ESCC tissues and could serve as a promising biomarker for identifying individuals with poor prognostic potential.

The objective of this study was to investigate the prognostic value of peripheral blood monocytes in esophageal squamous cell carcinoma (ESCC) patients who underwent esophagectomy. Records from 218 consecutive patients with histologically diagnosed ESCC who underwent esophagectomy at Qilu Hospital of Shandong University from January 2007 to December 2008 were retrospectively reviewed. The median disease-free survival (DFS) of this cohort was 29.0 months, and the 5-year DFS rate was 34.4%. The median overall survival (OS) was 35.0 months, and the 5-year OS rate was 37.6%. The cut-off value of 0.42 × 10 /L for the absolute monocyte count (AMC) was chosen as optimal to discriminate between survival and death by applying receiver operating curve analysis. There were 131 patients (60.1%) who had high AMC (≥0.42 × 10 /L) preoperatively. We found that AMC was significantly associated with gender, tumor location, and platelet count. Kaplan-Meier survival analysis of patients with high preoperative AMC had a significant worse prognosis for DFS (high vs. low: 27.5% vs. 39.0%, P = 0.015) and OS (high vs. low: 31.1% vs. 44.8%, P = 0.009) than those with low preoperative AMC. In a multivariate analysis, preoperative AMC was an independent prognostic factor for DFS (P = 0.025, hazard ratio [HR]: 1.469, 95% confidence interval [CI]: 1.050-2.054) and OS (P = 0.015, HR: 1.547, 95% CI: 1.088-2.200). In addition, among 140 patients without both preoperative and postoperative therapy, significantly worse OS (P = 0.012) and marginally reduced DFS (P = 0.079) were found in the high AMC cohort versus the low AMC cohort. A higher preoperative absolute peripheral monocyte count can be considered as a useful prognostic marker of ESCC patients who underwent esophagectomy.