Association between Dietary Behavior and Esophageal Squamous Cell Carcinoma in Yanting

Zhao, Lin,Liu, Chun-Ling,Song, Qing-Kun,Deng, Ying-Mei,Qu, Chen-Xu,Li, Jun Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.20

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.

VEGF-C and VEGF-D Expression and its Correlation with Lymph Node Metastasis in Esophageal Squamous Cell Cancer Tissue

Yang, Zeng,Wang, Yong-Gang,Su, Kai Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.1

Background: To explore vascular endothelial growth factor C (VEGF-C) and VEGF-D expression and its correlation with lymph node metastasis in esophageal squamous cell cancer (ESCC) tissue. Materials and Methods: Immunohistochemical methods were applied to detect the levels of VEGF-C and VEGF-D expression in 64 surgicall removal ESCC tissues, tissues adjacent to cancer and normal tissues, and the relationship between VEGF-C and VEGF-D expression and lymph node metastasis was analyzed. Results: Both VEGF-C and VEGF-D were expressed by varying degrees in esophageal cancer tissue, the tissue adjacent to cancer and normal tissue, and the positive expression rate went down successively. The positive expression rates of VEGF-C (59.4%) and VEGF-D (43.8%) in esophageal cancer tissue were significantly higher than in the tissue adjacent to cancer (34.4%, 15.6%) and normal tissue (20.3%, 12.5%), respectively, in which significant differences were manifested (p<0.01). Positive expression rates of VEGF-C and VEGF-D in esophageal cancers with lymph node metastasis were markedly higher than without such metastasis (p<0.01), while those in the tissue with TNM staging I~II were markedly lower than that with TNM staging III~IV (p<0.01). Conclusions: Both VEGF-C and VEGF-D are highly expressed in ESCC tissue, which may be related to the lymph node metastasis of cancer cells. Hence, VEGF-C and VEGF-D can be clinically considered as important reference indexes of lymph node metastasis in esophageal cancer.

Overexpression of Phospholipase A₂ Group IIA in Esophageal Squamous Cell Carcinoma and Association with Cyclooxygenase-2 Expression

Zhai, Yan-Chun,Dong, Bin,Wei, Wen-Qiang,He, Yan,Li, Xin-Qing,Cormier, Robert T.,Wang, Wei,Liu, Fen Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.21

Background: Esophageal cancer is one of the most frequently occurring malignancies and the seventh leading cause of cancer-related deaths in the world. The esophageal squamous cell carcinoma (ESCC) is the most common histological type of esophageal cancer worldwide. Materials and Methods: Our goal in this study was to detect phospholipase A2 Group IIA (PLA2G2A) and cyclooxygenase-2 (COX-2) immuno-expression in ESCC in a high-risk population in China. Results: Positive expression of PLA2G2A protein was observed in 57.2% (166/290) of the cases, while COX-2 was found in 257 of 290 samples (88.6%), both PLA2G2A and COX-2 being expressed in 153 cases (52.8%), with a significant agreement (Kappa=0.091, p=0.031).Overexpression of PLA2G2A was significantly correlated with the depth of invasion (p=0.001). Co-expression of PLA2G2A and COX-2 not only significantly correlated with the depth of invasion (p=0.004) but also with TNM stage (p=0.04). Conclusions: Our results showed that in patients with ESCC, PLA2G2A overexpression and PLA2G2A co-expression with COX-2 is significantly correlated with advanced stage. The biological role and pathophysiologic regulation of PLA2G2A and COX-2 overexpression in ESCC deserve further investigation.

Matrix Metalloproteinase-13 - A Potential Biomarker for Detection and Prognostic Assessment of Patients with Esophageal Squamous Cell Carcinoma

Sedighi, Maryam,Aledavood, Seyed Amir,Abbaszadegan, MR,Memar, Bahram,Montazer, Mehdi,Rajabian, Majid,Gholamin, Mehran Asian Pacific Journal of Cancer Prevention 2016 Asian Pacific journal of cancer prevention Vol.17 No.6

Background: Matric metalloproteinase (MMP) 13 gene expression is increased in esophageal squamous cell carcinomas (ESCCs) and associated with increasing tumor invasion, lymph node involvement and decreased survival rates. Levels of the circulating enzyme may be elevated and used as a marker of tumor progression. In this study, clinical application of MMP-13 serum levels was evaluated for early detection, prediction of prognosis and survival time of ESCC patients. Materials and Methods: Serum levels of MMP13 were determined by ELISA in 66 ESCC patients prior of any treatment and 54 healthy controls for comparison with clinicopathological data through statistical analysis with Man Whitney U and Log-Rank tests. In addition, clinical value of MMP13 levels for diagnosis was evaluated by receiver operating characteristic (ROC) test. Results: The serum level of MMP-13 in patients (>250 pg/ml) was significantly higher than in the control group (<100 pg/ml) (p value=0.004). Also the results showed a significant correlation between MMP-13 serum levels with tumor stage (p value = 0.003), depth of tumor invasion (p value=0.008), involvement of lymph nodes (p value = 0.011), tumor size (p value = 0.018) and survival time. While there were no significant correlation with grade and location of tumors. ROC analysis showed that MMP-13 level is an accurate diagnostic marker especially to differentiate pre-invasive/ invasive lesions from normal controls (sensitivity and specificity: 100%). Conclusions: These findings indicate a potential clinical significance of serum MMP13 measurement for early detection and prognostic assessment in ESCC patients.

Association of Single Nucleotide Polymorphisms in the Prostaglandin-endoperoxide Synthase 2 (PTGS2) and Phospholipase A₂ Group IIA (PLA2G2A) Genes with Susceptibility to Esophageal Squamous Cell Carcinoma

Liu, Fen,Wei, Wen-Qiang,Cormier, Robert T.,Zhang, Shu-Tian,Qiao, You-Lin,Li, Xin-Qing,Zhu, Sheng-Tao,Zhai, Yan-Chun,Peng, Xiao-Xia,Yan, Yu-Xiang,Wu, Li-Juan,He, Dian,He, Yan Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.4

Background: The prostaglandin-endoperoxide synthase 2 (PTGS2) and phospholipase A2 group IIA (PLA2G2A) genes encode enzymes that are involved in arachidonic acid and prostaglandin biosynthesis. Dysregulation of both genes is associated with inflammation and carcinogenesis, including esophageal squamous cell carcinoma (ESCC). We therefore hypothesized that there is an association between single nucleotide polymorphisms (SNPs) in these genes and susceptibility to ESCC. Methods: We performed a gene-wide tag SNP-based association study to examine the association of SNPs in PTGS2 and PLA2G2A with ESCC in 269 patients and 269 healthy controls from Taihangshan Mountain, Henan and Hebei Provinces, the rural area of China which has the highest incidence of esophageal cancer in the world. Thirteen tag SNPs in PLA2G2A and 4 functional SNPs in PTGS2 were selected and genotyped using a high-throughput Mass Array genotyping platform. Results: We found a modest increased risk of ESCC in subjects with the PTGS2 rs12042763 AA genotype (OR=1.23; 95% CI, 1.00-3.04) compared with genotype GG. For PLA2G2A, a decreased risk of ESCC was observed in subjects with the rs11677 CT (OR=0.51, 95%CI, 0.29-0.85) or TT genotype (OR=0.51, 95%CI, 0.17-0.96) or the T carriers (CT+TT) (OR=0.52, 95%CI, 0.31-0.85) when compared with the CC genotype. Also for PLA2G2A, rs2236771 C allele carriers were more frequent in the control group (P=0.02). Subjects with the GC (OR=0.55, 95%CI, 0.33-0.93) or CC genotype (OR=0.38, 95% CI, 0.16-0.94) or the C carriers (GC+CC) (OR=0.52, 95%CI, 0.32-0.85) showed a negative association with ESCC susceptibility. Conclusions: Our results suggest that PTGS2 and PLA2G2A gene polymorphisms may modify the risk of ESCC development.

Weight Loss Correlates with Macrophage Inhibitory Cytokine-1 Expression and Might Influence Outcome in Patients with Advanced Esophageal Squamous Cell Carcinoma

Lu, Zhi-Hao,Yang, Li,Yu, Jing-Wei,Lu, Ming,Li, Jian,Zhou, Jun,Wang, Xi-Cheng,Gong, Ji-Fang,Gao, Jing,Zhang, Xiao-Tian,Li, Jie,Li, Yan,Shen, Lin Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.15

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.

Anti-CSC Effects in Human Esophageal Squamous Cell Carcinomas and Eca109/9706 Cells Induced by Nanoliposomal Quercetin Alone or Combined with CD 133 Antiserum

Zheng, Nai-Gang,Mo, Sai-Jun,Li, Jin-Ping,Wu, Jing-Lan Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.20

CD133 was recently reported to be a cancer stem cell and prognostic marker. Quercetin is considered as a potential chemopreventive agent due to its involvement in suppression of oxidative stress, proliferation and metastasis. In this study, the expression of CD133/CD44 in esophageal carcinomas and Eca109/9706 cells was explored. In immunoflurorescence the locations of $CD133^+$ and multidrug resistance 1 $(MDR1)^+$ in the same E-cancer cells were coincident, mainly in cytomembranes. In esophageal squamous cell carcinomas detected by double/single immunocytochemistry, small $CD133^+$ cells were located in the basal layer of stratified squamous epithelium, determined as CSLC (cancer stem like cells); $CD44^+$ surrounding the cells appeared in diffuse pattern, and the larger $CD44^+$ (hi) cells were mainly located in the prickle cell layer of the epithelium, as progenitor cells. In E-cancer cells exposed to nanoliposomal quercetin (nLQ with cytomembrane permeability), down-regulation of NF-${\kappa}Bp65$, histone deacetylase 1 (HDAC1) and cyclin D1 and up-regulation of caspase-3 were shown by immunoblotting, and attenuated HDAC1 with nuclear translocation and promoted E-cadherin expression were demonstrated by immunocytochemistry. In particular, enhanced E-cadherin expression reflected the reversed epithelial mesenchymal transition (EMT) capacity of nLQ, acting as cancer attenuator/preventive agent. nLQ acting as an HDAC inhibitor induced apoptotic cells detected by TUNEL assay mediated via HDAC-NF-${\kappa}B$ signaling. Apoptotic effects of liposomal quercetin (LQ, with cytomembrane-philia) combined with CD133 antiserum were also detected by CD133 immunocytochemistry combined with TUNEL assay. The combination could induce greater apoptotic effects than nLQ induced alone, suggesting a novel anti-CSC treatment strategy.

Upregulation of STK15 in Esophageal Squamous Cell Carcinomas in a Mongolian Population

Chen, Guang-Lie,Hou, Gai-Ling,Sun, Fei,Jiang, Hong-Li,Xue, Jin-Feng,Li, Xiu-Shen,Xu, En-Hui,Gao, Wei-Shi,Cao, Jian-Ping Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.15

Background: The STK15 gene located on chromosome 20q13.2 encodes a centrosome-associated kinase critical for regulated chromosome segregation and cytokinesis. Recent studies have demonstrated STK15 to be significantly associated with many tumors, with aberrant expression obseved in many human malignancies. The purpose of this study was to investigate expression of STK15 in esophageal squamous cell carcinomas (ESCCs) in a Mongolian population. Methods: Two non-synonymous single nucleotide polymorphisms in the coding region of STK15, rs2273535 (Phe31Ile) and rs1047972 (Val57Ile) were assessed in 380 ESCC patients and 380 healthy controls. We also detected STK15 mRNA expression in 39 esophageal squamous cell carcinomas and corresponding adjacent tissues by real time PCR. Results: rs2273535 showed a significant association with ESCC in our Mongolian population (rs227353, P allele = 0.0447, OR (95%CI) = 1.259 (1.005~1.578)). Real time PCR analysis of ESCC tissues showed that expression of STK15 mRNA in cancer tissues was higher than in normal tissues (p = 0.013). Conclusions: Our study showed that functional SNPs in the STK15 gene are associated with ESCC in a Mongolian population and up-regulation of STK15 mRNAoccurs in ESCC tumors compared adjacent normal tissues. STK15 may thus have an important role in the prognosis of ESCC and be a potential therapeutic target.

Protein-protein Interaction Network Analyses for Elucidating the Roles of LOXL2-delta72 in Esophageal Squamous Cell Carcinoma

Wu, Bing-Li,Zou, Hai-Ying,Lv, Guo-Qing,Du, Ze-Peng,Wu, Jian-Yi,Zhang, Pi-Xian,Xu, Li-Yan,Li, En-Min Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.5

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.

Pre-treatment Metabolic Tumor Volume and Total Lesion Glycolysis are Useful Prognostic Factors for Esophageal Squamous Cell Cancer Patients

Li, Yi-Min,Lin, Qin,Zhao, Long,Wang, Li-Chen,Sun, Long,Dai, Ming-Ming,Luo, Zuo-Ming,Zheng, Hua,Wu, Hua Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.3

Objectives: To study application of the maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV) and total lesion glycolysis (TLG) with $^{18}F$-FDG PET/CT for predicting prognosis of esophageal squamous cell cancer (ESC) patients. Methods: Eighty-six patients with ESC staged from I to IV were prospectively enrolled. Cisplatin-based chemoradiotherapy (CCRT) or palliative chemoradiotherapy were the main treatment methods and none received surgery. $^{18}F$-FDG PET/CT scans were performed before the treatment. SUVmax, MTV, and TLG were measured for the primary esophageal lesion and regional lymph nodes. Receiver operating characteristic curves (ROCs) were generated to calculate the P value of the predictive ability and the optimal threshold. Results: MTV and TLG proved to be good indexes in the prediction of outcome for the ESC patients. An MTV value of 15.6 ml and a TLG value of 183.5 were optimal threshold to predict the overall survival (OS). The areas under the curve (AUC) for MTV and TLG were 0.74 and 0.70, respectively. Kaplan-Meier analysis showed an MTV less than 15.6 ml and a TLG less than 183.5 to indicate good media survival time (p value <0.05). In the stage III-IV patient group, MTV could better predict the OS (P < 0.001), with a sensitivity and specificity of 0.80 and 0.67, respectively. Conclusions: Pre-treatment MTV and TLG are useful prognostic factors in nonsurgical ESC.