• Asian Pacific Journal of Cancer Prevention
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• v.16 no.12
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• pp.5089-5094
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• 2015

FADS1 (fatty acid desaturase 1) plays a crucial role in fatty acid metabolism, and it was recently reported to be involved in tumorigenesis. However, the role of FADS1 expression in esophageal squamous cell carcinoma (ESCC) remains unknown. In the current study, we investigated the expression and clinical pathologic and prognostic significance of FADS1 in ESCC. Immunohistochemical analyses revealed that 58.2% (146/251) of the ESCC tissues had low levels of FADS1 expression, whereas 41.8% (105/251) exhibited high levels of FADS1 expression. In positive cases, FADS1 expression was detected in the cytoplasm of cells. Correlation analyses demonstrated that FADS1 expression was significantly correlated with tumor location (p=0.025) but not with age, gender, histological grade, tumor status, nodal status or TNM staging. Furthermore, patients with tumors expressing high levels of FADS1had a longer disease-free survival time (p<0.001) and overall survival time (p <0.001). Univariate and multivariate analyses revealed that, along with nodal status, FADS1 expression was an independent and significant predictive factor (p<0.001). In conclusion, our study suggested that FADS1 might be a valuable biomarker and potential therapeutic target for ESCC.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.13
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• pp.5437-5442
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• 2014

Esophageal squamous cell carcinoma (ESCC) is one of the most malignancies with a poor prognosis. The phospholipase $C{\varepsilon}$ gene (PLCE1) encodes a novel ras-related protein effector mediating the effects of R-Ras on the actin cytoskeleton and membrane protrusion. However, molecular mechanisms pertinent to ESCC are unclear. We therefore designed PLCE1-special small interfering RNA and transfected to esophageal squamous cell (EC) 9706 cells to investigat the effects of PLCE1 gene silencing on the cell cycle and apoptosis of ESCC and indicate its important role in the development of ESCC. Esophageal cancer tissue specimens and normal esophageal mucosa were obtained and assayed by immunohistochemical staining to confirm overexpression of PLCE1 in neoplasias. Fluorescence microscopy was used to examine transfection efficiency, while the result of PLCE1 silencing was examined by reverse transcription (RT-PCR). Flow cytometry and annexin V apoptosis assays were used to assess the cell cycle and apoptosis, respectively. Expression of cyclin D1 and caspase-3 was detected by Western-blotting. The level of PLCE1 protein in esophageal cancer tissue was significantly higher than that in normal tissue. After transfection, the expression of PLCE1 mRNA in EC 9706 was significantly reduced, compared with the control group. Furthermore, flow cytometry results suggested that the PLCE1 gene silencing arrested the cell cycle in the G0/G1 phase; apoptosis was significantly higher than in the negative control group and mock group. PLCE1 gene silencing by RNAi resulted in decreased expression of cyclin D1 and increased expression of caspase-3. Our study suggests that PLCE1 may be an oncogene and play an important role in esophageal carcinogenesis through regulating proteins which control cell cycling and apoptosis.

• Journal of Digestive Cancer Research
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• v.11 no.2
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• pp.61-65
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• 2023

Globally, esophageal cancer is the seventh most common cancer, and the male-to-female ratio in esophageal adenocarcinoma (EAC) is significantly imbalanced at 4:1 to 8:1. Obesity, reflux, and smoking are known risk factors for this sex difference; however, fully explaining this remains challenging. Studies have investigated the link between exogenous sex hormones and esophageal cancer occurrence. A meta-analysis revealed a lower risk of EAC in female who had undergone hormone replacement therapy. Androgen-deprivation therapy in patients with prostate cancer was associated with a decreased risk of EAC. Tissue-based studies have reported varied results regarding the relationship between estrogen receptor expression and survival in female patients with esophageal squamous cell carcinoma (ESCC). Circulating hormone studies have suggested that higher testosterone and luteinizing hormone levels decreased EAC risk in men, and free testosterone was inversely correlated in female with ESCC. However, a high androgen-estrogen ratio in male patients with EAC was linked to increased odds of EAC. Sex hormones influence carcinogenesis, affecting cell proliferation, differentiation, metabolism, inflammation, and cell death. The studies were limited by the small sample size and varying hormone measurement methods; thus, future studies with definitive conclusions on the association between esophageal cancer and sex hormones are warranted.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.9
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• pp.4217-4222
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• 2016

Purpose: To compare the expression level of CK 15 in normal esophageal and esophageal squamous-cell carcinoma (ESCC) tissues and analyse possible functions of CK15 in occurrence and development. Materials and Methods: Immunohistochemistry was used to compare CK14, CK15 and proliferating cell nuclear antigen (PCNA) expression levels in ESCCs. Expression level of CK15 was also assessed by Western blotting. In addition, levels of CK15, cytokeratin 19 fragment antigen 21-1 (CYFRA21-1) and PCNA were detected in serum by enzymelinked immunosorbent assay (ELISA) and chemiluminescence methods. Relationships between clinicopathological parameters and CK14 and CK15 expression were then analyzed. Results: According to immunohistochemistry, in esophageal and intraepithelial neoplasia (SIN) tissues, the expression of CK14, CK15 and PCNA localized to basal layer of the epithelium. CK14 and CK15 levels were higher in normal esophageal squamous epithelial tissue than in SIN and ESCC, and greater in highly differentiated than poorly differentiated carcinoma tissue. By Western blotting, we found more pronounced expression of CK15 in normal esophageal tissue, compared with carcinoma tissue. The specificity of changed CK15 and CYFRA21-1 expression was respectively 90.0% and 96.7% in serum of ESCC patients. Joint detection could improve the sensitivity of esophageal carcinoma diagnosis. Relationships between CK14, CK15 expression and clinical parameters were not statistically significant (P>0.05). Postoperative survival in patients of CK14, CK15 positive expression was longer than with negative expression ($x^2=4.35$, P=0.037; $x^2=9.852$, P=0.002). Conclusions: CK15 expression decreased in esophageal squamous cell carcinoma tissue and serum of esophageal squamous carcinoma patients. We infer that CK15 may play an important role for the occurrence and development of esophageal squamous-cell carcinoma. In the future, CK15 may be used for the diagnosis, treatment and prognostic evaluation of esophageal squamous-cell carcinoma.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.20
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• pp.8657-8660
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• 2014

Background: Yanting is one of high risk areas for esophageal cancer and the screening program was therefore initiated there. This study was aimed to investigate the dietary behaviors on the risk of esophageal squamous cell carcinoma (ESCC), among the individuals with normal and abnormal esophagus mucosa. Materials and Methods: A frequency matched case-controls study was proposed to estimate the different distribution of dietary behavior between individuals of control, esophagitis and cancer groups. Cancer cases were selected from hospitals. Esophagitis cases and controls were selected from screening population for ESCC. Health workers collected data for 1 year prior to interview, in terms of length of finishing a meal, temperature of eaten food and interval between water boiling and drinking. Chi-square, Kruskal-Wallis tests and unconditional logistic regression model were used to estimate differences and associations between groups. Results: Compared with controls, length of finishing a meal ${\geq}15mins$ was related to a reduced OR for cancer (OR=0.46, 95%CI, 0.22-0.97) and even compared with cases of esophagitis, the OR of cancer was reduced to 0.30 (95%CI, 0.13-0.72). The OR for often eating food at a high temperature was 2.48 (95%CI 1.06, 5.82) for ESCC as compared with controls. Interval between water boiling and drinking of ${\geq}10mins$ was associated with lower risk of cancer: the OR was 0.18 compared with controls and 0.49 with esophagitis cases (p<0.05). Conclusions: Length of eating food ${\geq}15mins$ and interval between water boiling and drinking ${\geq}10mins$ are potentially related to reduced risk of esophageal SCC, compared with individuals with normal and abnormal esophageal mucosa. Recommendations to Yanting residents to change their dietary behaviors should be made in order to reduce cancer risk.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.2
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• pp.819-823
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• 2014

Objective: The aim was to evaluate roles of vitamin D3 (VD3) and beta-carotene (BC) in the development of esophageal squamous cell carcinoma (ESCC) in a high-risk area, Huai'an District, Huai'an City, China. Methods: 100 new ESCC diagnosed cases from 2007 to 2008 and 200 residency- age-, and sex-matched healthy controls were recruited. Data were collected from questionnaires, including a food frequency questionnaire (FFQ) to calculate the BC intake, and reversed phase high-performance liquid chromatography (RP-HPLC) was used to measure the serum concentrations of BC and VD3. Odds ratios (OR) and 95% confidence intervals (CI) were calculated in conditional logistic regression models. Results: The average dietary intake of BC was $3322.9{\mu}g$ (2032.4-5734.3) in the case group and $3626.8{\mu}g$ (1961.9-5827.9) in control group per capita per day with no significant difference by Wilcoxon test (p>0.05). However, the levels of VD3 and BC in the case group were significantly lower than in the control group (p<0.05). The OR values of the highest quartile and the lowest quartile of VD3 and BC in serum samples were both 0.13. Conclusion: Our results add to the evidence that high circulating levels of VD3 and BC are associated with a reduced risk of ESCC in this Chinese population.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.3
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• pp.1951-1955
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• 2013

Background: Associations between the methylenetetrahydrofolate reductase (MTHFR) A1298C polymorphism and esophageal cancer risk have been reported in many articles recently, but results were controversial. Therefore the present meta-analysis was conducted to to provide a more precise estimation. Methods: Odds ratios (ORs) with 95% confidence intervals (CIs) were used to evaluate the strength of associations. Results: Finally, six case-control studies involving a total of 1,302 cases and 2,391controls for the A1298C polymorphism were included. The meta-analysis showed that significantly increased risk for Asians (CC versus AA, OR=3.799, 95%CI=1.541-9.365, P=0.004; CCversusCA+AA, OR=3.997, 95%CI=1.614-9.900, P=0.003) and Caucasians (CC versus AA, OR=1.797, 95%CI=1.335-2.418, P=0.000; CC+CA versus AA,OR=1.240, 95%CI=1.031-1.492, P=0.022; CCversusCA+AA, OR=1.693, 95%CI=1.280-2.240, P=0.000). In addition, there was an association with risk for both ESCC (CC versus AA, OR=2.529, 95%CI=1.688-3.788, P=0.000; CCversusCA+AA, OR=2.572, 95%CI=1.761-3.758, P=0.000) and esophageal adenocarcinoma (EAC) (CC versus AA, OR=1.592, 95%CI=1.139-2.227, P=0.007; CC+CA versus AA,OR=1.247, 95%CI=1.016-1.530, P=0.035; CCversusCA+AA, OR=1.466, 95%CI=1.069-2.011, P=0.018). Conclusion: This meta-analysis suggested associations of the A1298C polymorphism with increased risk of esophageal cancer in both Asians and Caucasians. In addition, we found that the MTHFR A1298C polymorphism might influence risk ofESCC and EAC in the overall studies.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.13
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• pp.5445-5451
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• 2015

Fascin-1 (FSCN1) is an actin-bundling protein that induces cell membrane protrusions, increases cell motility, and is overexpressed in various human epithelial cancers, including esophageal squamous cell carcinoma (ESCC). We analyzed various protein-protein interactions (PPI) of differentially-expressed genes (DEGs), in fascin knockdown ESCC cells, to explore the role of fascin overexpression. The node-degree distributions indicated these PPI sub-networks to be characterized as scale-free. Subcellular localization analysis revealed DEGs to interact with other proteins directly or indirectly, distributed in multiple layers of extracellular membrane-cytoskeleton/ cytoplasm-nucleus. The functional annotation map revealed hundreds of significant gene ontology (GO) terms, especially those associated with cytoskeleton organization of FSCN1. The Random Walk with Restart algorithm was applied to identify the prioritizations of these DEGs when considering their relationship with FSCN1. These analyses based on PPI network have greatly expanded our comprehension of the mRNA expression profile following fascin knockdown to future examine the roles and mechanisms of fascin action.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.5
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• pp.2345-2351
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• 2014

Lysyl oxidase-like 2 (LOXL2), a member of the lysyl oxidase (LOX) family, is a copper-dependent enzyme that catalyzes oxidative deamination of lysine residues on protein substrates. LOXL2 was found to be overexpressed in esophageal squamous cell carcinoma (ESCC) in our previous research. We later identified a LOXL2 splicing variant LOXL2-delta72 and we overexpressed LOXL2-delta72 and its wild type counterpart in ESCC cells following microarray analyses. First, the differentially expressed genes (DEGs) of LOXL2 and LOXL2-delta72 compared to empty plasmid were applied to generate protein-protein interaction (PPI) sub-networks. Comparison of these two sub-networks showed hundreds of different proteins. To reveal the potential specific roles of LOXL2- delta72 compared to its wild type, the DEGs of LOXL2-delta72 vs LOXL2 were also applied to construct a PPI sub-network which was annotated by Gene Ontology. The functional annotation map indicated the third PPI sub-network involved hundreds of GO terms, such as "cell cycle arrest", "G1/S transition of mitotic cell cycle", "interphase", "cell-matrix adhesion" and "cell-substrate adhesion", as well as significant "immunity" related terms, such as "innate immune response", "regulation of defense response" and "Toll signaling pathway". These results provide important clues for experimental identification of the specific biological roles and molecular mechanisms of LOXL2-delta72. This study also provided a work flow to test the different roles of a splicing variant with high-throughput data.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.15
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• pp.6047-6052
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• 2014

Background: Weight loss during chemotherapy has not been exclusively investigated. Macrophage inhibitory cytokine-1 (MIC-1) might play a role in its etiology. Here, we investigated the prognostic value of weight loss before chemotherapy and its relationship with MIC-1 concentration and its occurrence during chemotherapy in patients with advanced esophageal squamous cell carcinoma (ESCC). Materials and Methods: We analyzed 157 inoperable locally advanced or metastatic ESCC patients receiving first-line chemotherapy. Serum MIC-1 concentrations were assessed before chemotherapy. Patients were assigned into two groups according to their weight loss before or during chemotherapy:>5% weight loss group and ${\leq}5%$ weight loss group. Results: Patients with weight loss>5% before chemotherapy had shorter progression-free survival period (5.8 months vs. 8.7 months; p=0.027) and overall survival (10.8 months vs. 20.0 months; p=0.010). Patients with weight loss >5% during chemotherapy tended to have shorter progression-free survival (6.0 months vs. 8.1 months; p=0.062) and overall survival (8.6 months vs. 18.0 months; p=0.022), and if weight loss was reversed during chemotherapy, survival rates improved. Furthermore, serum MIC-1 concentration was closely related to weight loss before chemotherapy (p=0.001) Conclusions: Weight loss both before and during chemotherapy predicted poor outcome in advanced ESCC patients, and MIC-1 might be involved in the development of weight loss in such patients.