The results of the present study suggest that TRPV2 is involved in the maintenance of CSCs, and that its specific inhibitor, tranilast, has potential as a targeted therapeutic agent against esophageal squamous cell carcinoma.

Background: Transient receptor potential vanilloid 2 (TRPV2) was recently shown to be involved in migrant potentials. The present study aimed to investigate its role in esophageal squamous cell carcinoma (ESCC). Methods: Knockdown experiments were conducted using TRPV2 siRNA in human ESCC cell lines, and anti-tumor effects were analyzed. The gene expression profiles of cells were analyzed using a microarray method. An immunohistochemical staining was performed on 62 primary tumor samples. Results: TRPV2 overexpression was observed in TE15 and KYSE170 cells. TRPV2 depletion suppressed proliferation, cell cycle progression, and invasion/migration ability, and induced apoptosis. A pathway analysis of microarray data showed that TRPV2 depletion down-regulated WNT/β-catenin signaling-related genes and basal cell carcinoma signaling-related genes. The suppression of tumor functions, such as proliferation, invasion, and angiogenesis, was predicted in the ontology analysis. Immunohistochemical analysis revealed a correlation between strong TRPV2 expression and a poor prognosis in ESCC patients. Conclusion: The present results suggest that TRPV2 regulates cancer progression by affecting WNT/β-catenin or basal cell carcinoma signaling, and that TRPV2 strong expression is associated with a worse prognosis in ESCC patients. These results provide an insight into the role of TRPV2 as a novel therapeutic target or biomarker for ESCC.

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PET-CT appears to be a useful complementary modality in the assessment of pStage III/IV because of the high sensitivity of FDG uptake in the primary tumor and the high specificity of FDG uptake in the lymph nodes.

Recent studies have described important roles for the anion exchanger (AE) in epithelial carcinogenesis and tumor behavior. The objectives of the present study were to investigate the role of AE1 in the regulation of genes involved in tumor progression and the clinicopathological significance of its expression in esophageal squamous cell carcinoma (ESCC). An immunohistochemical analysis was performed on 61 primary tumor samples obtained from ESCC patients who underwent esophagectomy. AE1 was primarily located in the cell membranes or cytoplasm of carcinoma cells, and its distribution pattern was related to the histological degree of the differentiation of SCC or the pT category. Among patients with pT2-3 ESCC, the 5-year survival rate of patients with diffuse AE1 expression (40.2%) was significantly lower than that of patients with focal expression (74.0%). AE1 was strongly expressed in KYSE150 and TE8 human ESCC cells. The depletion of AE1 using siRNA inhibited cell proliferation, migration, and invasion and induced apoptosis. The results of the microarray analysis revealed that MAPK and Hedgehog signaling pathway-related genes, such as DHH, and GLI1, were down-regulated in AE1-depleted KYSE150 cells. In conclusions, the results of the present study suggest that the diffuse expression of AE1 is related to a worse prognosis in patients with advanced ESCC, and that it regulates tumor progression by affecting MAPK and Hedgehog signaling pathways. These results provide an insight into the role of AE1 as a mediator of and/or a biomarker for ESCC.

Aim: Diffusion-weighted MRI (DWI) has the potential to reveal intra-tumor structural heterogeneity consisting of stroma through an evaluation of uniformity on DWI. In present study, we examined the diagnostic value of intra-tumor heterogeneity evaluated by DWI in lower rectal cancer (LRC).Patients and Methods: A total of 172 LRC patients underwent radical surgery between 2009 and 2017. T1 tumors and cases without pre-operative MRI were excluded. Twenty-nine primary resection cases (PR) and 37 pre-operative chemoradiotherapy followed by radical surgery cases (pCRT) were targeted. Intra-tumor heterogeneity on DWI was quantified using a specific formula (HSD). Structural heterogeneity was objectively quantified by an image analysis of resected specimens using a digital microscope (HSP). The relationships between HSD and HSP, pathological factors, and tumor regression grades (TRG) of pCRT were evaluated.Results: The relationship between HSD and HSP was analyzed by a linear regression model in PR cases, revealing a positive correlation (R2=0.43). PR cases were divided into HSD-high and HSD-low according to the median. There were more pT3 or N(+) cases in HSD-high (p=0.038, 0.095). HSD before pCRT correlated with TRG (grade 1 versus 2/3) in pCRT cases (p=0.001). The diagnostic accuracy of HSD for predicting T and N stages and therapeutic grades was evaluated by cut-off values calculated using a ROC curve and revealed that each factor may be accurately diagnosed.Conclusion: Intra-tumor heterogeneity on DWI corresponded with stromal pathological heterogeneity. It is useful for predicting T3 or deeper tumor invasion, pathological N(+), and the therapeutic effects of pCRT.

BackgroundPrecise staging is indispensable to select the appropriate treatment strategy for gastric cancer (GC); however, the diagnostic accuracy of conventional modalities needs to be improved. This study investigated the clinical significance of the preoperative neutrophil-to-lymphocyte ratio (NLR) for the prediction of pathological lymph node metastasis (pN+) in GC.MethodsThis was a retrospective study of 429 patients with GC who underwent curative gastrectomy. The predictive ability of NLR for pN+ was examined in comparison with that of computed tomography.ResultsThe preoperative NLR ranged from 0.6 to 10.8 (median, 2.0), and the optimal cut-off value for predicting pN+ was 1.6 according to the receiver operating characteristic curve with the maximal Youden index. Multivariate analysis identified a NLR ≥ 1.6 (odds ratio (OR) 3.171; 95% confidence interval (CI) 1.448–7.235, p = 0.004) and cN+ (OR 2.426; 95% CI 1.221–4.958, p = 0.011) to be independent factors associated with pN+ in advanced GC (cT2-T4). On the other hand, a NLR ≥ 1.6 was not useful for predicting pN+ in early GC (cT1). In advanced GC, a NLR ≥ 1.6 detected pN+ with a higher sensitivity (84.9%) and negative predictive value (NPV) (63.9%) than conventional modalities (50.0 and 51.7%, respectively). When the subjects were limited to those with advanced GC with cN0, the sensitivity and NPV of a NLR ≥ 1.6 for pN+ increased further (90.7 and 81.0%, respectively).ConclusionThe preoperative NLR may be a useful complementary diagnostic tool for predicting pN+ in advanced GC because of its higher sensitivity and NPV than conventional modalities.

Background/Aim: Few studies have examined postoperative CRP in esophageal cancer. We investigated the relationship between postoperative CRP values according to the postoperative period and prognosis in esophageal cancer. Patients and Methods: We performed a retrospective cohort study including 187 patients who underwent esophagectomy for esophageal squamous cell carcinoma (ESCC) between January 2008 and October 2016. Results: CRP within 1 month of surgery was not related to overall survival (OS) or recurrence-free survival (RFS). In a univariate analysis, postoperative 2 months (2M)-CRP ≥0.15 ml/dl was associated with poorer OS (41.4 vs. 71.4%, p=0.0002) and RFS (28.9 vs. 51.3%, p=0.007). In a multivariate analysis, 2M-CRP ≥0.15 ml/dl was an independent factor for poorer OS (HR=2.27, 95%CI=1.03-3.34, p=0.005) and RFS (HR=1.65, 95%CI=1.08-2.52, p=0.020). The incidence of postoperative pneumonia was significantly higher in the 2M-CRP ≥0.15 ml/dl group (p=0.026). Conclusion: 2M-CRP ≥0.15 ml/dl is an independent prognostic factor for ESCC. Furthermore, postoperative pneumonia may be associated with patient prognosis after esophagectomy.