Esophageal cancer (EC) is one of the common malignant tumors in China. Esophagectomy based on multi-disciplinary principle improves the quality of life and survival of esophageal cancer patients, but a lot of patients will suffer recurrence or metastasis after surgery. TNM stage is the most important factor which affects the prognosis of patients with esophageal cancer. Besides, there are other prognostic factors, such as abnormal expression of the proteins. Exploration of these proteins may provide new clues to improve prognosis in esophageal squamous cell cancer (ESCC). We reviewed the literatures related to abnormal protein expression in ESCC, and tried to elucidate the prognostic value and potential clinical application of these proteins in ESCC.
Biomarkers, Tumor ; metabolism ; Carcinoma, Squamous Cell ; metabolism ; Esophageal Neoplasms ; metabolism ; Humans ; Prognosis ; Proteins ; metabolism

OBJECTIVE: To investigate the expression of MC1R in esophageal squamous cell carcinoma and its correlation with the clinicopathological parameters. METHODS: We analyzed the expression of MC1R in esophageal cancer based on data from TCGA databse and examined its expression levels using RT-PCR and Western blotting in a human esophageal epithelial cell line BAr-T, human esophageal squamous cell carcinoma cell lines ECA109, KYSE30, KYSE150, KYSE510, TE-1, TE-13, and EC9706, a human gastric cancer cell line SGC7901 and 19 pairs of esophageal squamous cell carcinoma tissues and adjacent tissues.Immunohistochemistry was used to detect MC1R expression levels in 32 pairs of paraffin-embedded sections of esophageal squamous cell carcinoma and adjacent tissues, and the correlation of MC1R expression and the patients'clinicopathological characteristics was analyzed. RESULTS: Bioinformatics analysis showed that MC1R was significantly overexpressed in esophageal cancer tissues (P < 0.05).MC1R expression was also increased in 5 esophageal squamous cell carcinoma cell lines ECA109, KYSE30, KYSE510, TE-13, EC9706 and the gastric cancer cell line SGC7901 as compared with that in esophageal epithelial cells (P < 0.05).Immunohistochemistry revealed significantly increased MC1R expression in esophageal squamous cell carcinoma tissue sections in comparison with the adjacent tissue sections (P < 0.05).In patients with esophageal squamous cell carcinoma, a high MC1R expression was detected mainly in those with an old age, positive for middle-thoracic involvement, and with moderately differentiated tumor cells, and showed a correlation with T stage of tumor (P < 0.05), but not with the other clinicopathological parameters such as gender, age, degree of cell differentiation, primary tumor site, or TNM stage (P>0.05). CONCLUSION MC1R is highly expressed in esophageal squamous cell carcinoma and may serve as a molecular biomarker to assist in the diagnosis of esophageal squamous cell carcinoma.
Humans ; Esophageal Squamous Cell Carcinoma ; Esophageal Neoplasms/metabolism* ; Stomach Neoplasms ; Cell Line, Tumor ; Immunohistochemistry ; Cell Proliferation ; Gene Expression Regulation, Neoplastic

Carcinoma, Squamous Cell ; metabolism ; mortality ; Esophageal Neoplasms ; metabolism ; mortality ; Humans ; MicroRNAs ; metabolism ; Prognosis

OBJECTIVETo preliminarily investigate the expression and clinical significance of leptin and adiponectin in esophageal squamous cell carcinoma (ESCC).

METHODSThe expression of leptin and adiponectin in ESCC and normal esophageal mucosal tissue was detected by immunohistochemical staining with tissue microarray. The correlation between leptin, adiponectin and clinicalpathological features was statistically analyzed.

RESULTSThe expression of leptin was significantly upregulated in the ESCC than in the normal esophageal mucosa tissue [65.6% (80/122) versus 27.5% (11/40), P < 0.001]. Expression of leptin was significantly correlated with lymph node involvement and advanced tumor stage (P = 0.009 and P = 0.043, respectively). Expression of adiponectin was significantly down-regulated in ESCC compared with that in normal esophageal mucosal tissue [22.1% (27/122) versus 47.5% (19/40), P = 0.002]. Expression of adiponectin was significantly correlated with lymph node involvement (P = 0.020). Correlation analysis showed a positive correlation between the expression of leptin and lymph node metastasis and TNM stage (r = 0.235 and r = 0.183, respectively), and a negative correlation between the expression of adiponectin and lymph node metastasis (r = -0.229). There was no significant correlation between the expressions of leptin and adiponectin (P > 0.05), and between the body mass index and the expression of leptin and adiponectin, and lymph node metastasis (P > 0.05 for all).

CONCLUSIONSAn imbalanced expression of adipocytokines exits in ESCC. The expression of leptin and adiponectin is correlated with lymph node metastasis and/or tumor stage. Therefore, imbalanced expression of leptin and adiponectin may have a potential role in the carcinogenesis and disease progression of ESCC.

Adiponectin ; metabolism ; Carcinoma, Squamous Cell ; metabolism ; Down-Regulation ; Esophageal Neoplasms ; metabolism ; Leptin ; metabolism ; Lymphatic Metastasis ; Neoplasm Staging ; Up-Regulation

Esophageal Neoplasms ; metabolism ; pathology ; Female ; Humans ; Melanoma ; metabolism ; pathology ; Melanoma-Specific Antigens ; metabolism ; Middle Aged ; S100 Proteins ; metabolism

OBJECTIVETo investigate the expression of annexin I in esophageal squamous cell carcinoma (SCC) and carcinomas of other histological types in order to analyze the correlation between the expression of annexin I and carcinogenesis.

METHODSFirst, a set of tissue microarray was established, which consisted of SCC from the esophagus (208 cases), lung, larynx, cervix, and external genital organs; adenocarcinomas from the lung, stomach, colon and rectum, liver, pancreas, breast, thyroid and kidney with 30 cases in each group, meanwhile, the corresponding normal tissue was also obtained for control. Immunohistochemistry was used to detect the expression of annexin I in different types of carcinomas and the corresponding normal controls from different organs. The correlation between the expression of annexin I and the clinicopathological feature was analyzed and compared, which included age, gender, differentiation grade and lymph node metastasis.

RESULTSIt was found that the expression of annexin I was decreased in esophageal SCC, when compared with normal esophageal squamous epithelia (P < 0.001), the similarity was also found in SCC of the lung, larynx and cervix. However, though negative in normal epidermis, annexin I expression was detected in some cases with SCC from external genital organs. Annexin I was found to be overexpressed in adenocarcinomas of the lung, stomach, colon and rectum, liver, pancreas, breast, thyroid and kidney, particularly very strong expression of annexin I was seen in lung adenocarcinoma, uterine endometrioid adenocarcinoma and ovarian serous adenocarcinoma. Interestingly, it was found to be positive in all thyroid papillary carcinomas, but negative in all normal thyroid glands. However, annexin I expression was found to be negative in all hepatocellular carcinoma and normal hepatocytes; and it was only detected in myoepithelium of normal breast tissue, but not in ductal luminal cells, and rarely in infiltrating ductal adenocarcinoma. In SCC, annexin I expression was stronger in well differentiated ones than that in the poorly differentiated ones. However, contrasting with SCC, in the adenocarcinomas from different organs, annexin I expression was much stronger in poorly differentiated ones than that in the well differentiate ones, especially in the adenocarcinomas from stomach, colon and rectum, pancreas, ovarian and kidney.

CONCLUSIONAnnexin I expression is quite different among different types of carcinomas, and is correlated with histopathological type and differentiation grade. Further study is needed to investigate its role in the carcinogenesis.

Adenocarcinoma ; metabolism ; pathology ; Annexin A1 ; metabolism ; Carcinoma, Endometrioid ; metabolism ; pathology ; Carcinoma, Squamous Cell ; metabolism ; pathology ; Cell Differentiation ; Endometrial Neoplasms ; metabolism ; pathology ; Epithelium ; metabolism ; Esophageal Neoplasms ; metabolism ; pathology ; Esophagus ; metabolism ; Female ; Humans ; Immunohistochemistry ; Lung Neoplasms ; metabolism ; pathology ; Stomach Neoplasms ; metabolism ; pathology

OBJECTIVETo investigate the expression of HOXA13 gene in stage-II(a esophageal squamous cell carcinoma(ESCC), and to evaluate its relationship with clinicopathological characteristics and prognosis.

METHODSThe expression of HOXA13 was examined by immunohistochemistry(IHC) in specimens from 39 patients with ESCC of stage-II(a, who underwent resection from 1995 to 2002. SPSS software was used to analyze the relationship between HOXA13 expression and clinicopathological characteristics and prognosis of patients.

RESULTSThe expression of HOXA13 protein was detected in ESCC tissue, and the positive rate was 61.5%. The median survival time of patients without HOXA13 expression(>72 months) was significantly longer than those with HOXA13 expression (24 months)( P=0.023). Multivariate analysis showed that HOXA13 expression was independent predictor of disease-free survival time of patients with ESCC.

CONCLUSIONThe expression of HOXA13 can be detected in ESCC and is a negative independent predictor of disease-free survival, which implies that HOXA13 might play a role in ESSC, and may be used as a clinical tumor marker of ESCC.

Carcinoma, Squamous Cell ; metabolism ; pathology ; Esophageal Neoplasms ; metabolism ; pathology ; Female ; Homeodomain Proteins ; metabolism ; Humans ; Male ; Middle Aged ; Neoplasm Staging ; Prognosis

OBJECTIVETo establish the co-culture model of cancer cells and nerve, and to study the influence of esophageal cancer on nerve fibers.

METHODSMouse dorsal root ganglion (DRG) was cultured in sterile conditions by primary isolation. Co-culture model was established using matrigel matrix-embedded DRG and EC109 (esophageal cancer cell line) transfected with green fluorescent protein. Morphological changes of DRG, number and area of neurites were quantified with microscopy and image analysis. Furthermore, the mRNA expression of nerve growth factor(NGF) and brain derived neurotrophic factor(BDNF) was detected by real-time PCR.

RESULTSIn mixture cultivation model of EC109 and DRG cells, directional outgrowth of neurite projecting to EC109 was observed, and the length of neurite was markedly longer in proximal field compared to distal field. The number and area of neurite were 87 and 346 μm(2) in proximal field respectively, and 23 and 141 μm(2) in distal field on the 7th day. The expressions of NGF and BDNF were up-regulated in esophageal cancer cells.

CONCLUSIONSThe esophageal cancer may play an important role in nerve fiber growth and guidance, which may be associated with the up-regulation of NGF and BDNF expressions.

Animals ; Coculture Techniques ; Esophageal Neoplasms ; metabolism ; Ganglia, Spinal ; Humans ; Neurites ; Rats, Sprague-Dawley ; Up-Regulation

OBJECTIVEThe aim of this study was to explore the molecular mechanism of apoptosis in esophageal cancer cells induced by Isodon rubescens.

METHODSThe DNA-damage effect of Jaridonin was detected by single cell gel electrophoresis (SCGE). The p53 protein was determined by Western blot. GSH assay kit was employed to determine the GSH content in human esophageal cancer EC-1 cells. Intracellular levels of hydrogen peroxide (H2O2) or superoxide (O(2).-) were determined using the redox-sensitive probes 2', 7'-dichlorodihydrofluorescein diacetate (DCF) or dihydroethidium (DHE), and the fluorescence signal was assayed by fluorescence microscopy and by flow cytometry.

RESULTSJaridonin induced DNA damage in EC-1 cells remarkably. The olive tail moments (OTM) of control and 20, 40 µmol/L Jaridonin were 3.2, 45.2 and 89.0, respectively. Compared with the control, the differences were significant (P < 0.01 for both). Jaridonin resulted in extensive p53 up-regulation in the EC-1 cells. More importantly, the p53 up-regulation occurred as early as 2 h after Jaridonin incubation, and in a time-dependent manner (P < 0.05). p53 siRNA transfection inhibited apoptosis in the EC-1 cells, and the Jaridonin-induced apoptosis rate was reduced from 38.5% to 8.8%. Intracellular level of H2O2 was increased by Jaridonin, whereas the level of O(2).- was barely changed. The GSH content in EC-1 cells was reduced from (10.3 ± 1.6) nmol/mg protein to (4.6 ± 2.1) nmol/mg protein after 20 µmol/L Jaridonin incubation for 8 h, and it was further reduced with the increase of Jaridonin concentration. Jaridonin induced DNA damage, H2O2 accumulation and apoptosis were significantly attenuated in the presence of GSH, but Jaridonin showed little effect on normal human liver L-02 cells.

CONCLUSIONSJaridonin selectively induces apoptosis in esophageal cancer EC-1 cells through H2O2-mediated DNA damage by depleting GSH.

Antineoplastic Agents ; pharmacology ; Apoptosis ; DNA Damage ; Diterpenes, Kaurane ; pharmacology ; Esophageal Neoplasms ; metabolism ; Humans ; Hydrogen Peroxide ; metabolism ; Up-Regulation

OBJECTIVETo investigate the expression and significance of CCL5 in patients with esophageal carcinoma.

METHODSUsing reverse transcriptase polymerase chain reaction (RT-PCR), the expressions of CCL5/CD8/granzyme B/perforin in tumor and corresponding adjacent tissues from esophageal carcinoma patients were examined. Flow cytometry (FACS) was used to detect the percentages of CD8(+) T cells and CCR5(+)CD8(+) T cells in TIL and PBMC from the patients. Transwell assay was performed to study the effect of CCL5 on the migration of T cells in vitro. T test and Spearman correlation analysis were performed.

RESULTSThe mRNA expressions of CCL5 and perforin were 0.348 2 ± 0.300 1 and 0.181 9 ± 0.118 6, respectively, in the tumor samples, while their expressions in adjacent samples were 0.279 6 ± 0.138 0 and 0.118 0 ± 0.109 8, respectively, with no statistically significant differences between them (P > 0.05 for both). The mRNA expressions of CD8 and granzyme B were significantly higher in the tumor tissues than in adjacent tissues (0.464 9 ± 0.300 8 vs. 0.279 0 ± 0.173 4, 0.648 7 ± 0.516 0 vs. 0.469 7 ± 0.259 1; P < 0.05 for both). The relative expression of CCL5 was positively correlated with that of CD8, perforin and granzyme B (r(CD8) = 0.272, P = 0.034; r(perforin) = 0.305, P = 0.026; r(granzymeB) = 0.108, P = 0.012) in the tumor sites. FACS data revealed that the proportions of CD8(+) T cells in TIL and PBMC were (45.86 ± 16.09)% and (34.05 ± 15.07)%, respectively, showing a significant difference (P = 0.022). Similarly, CCR5(+)CD8(+) T cells fraction in TIL (48.12 ± 26.75)% was much higher than that in PBMC (19.53 ± 13.67) % (P < 0.001). Transwell assay showed that CCL5 protein enhanced the migration of T cells, supporting that CCL5 is crucial for CD8(+) T cells recruitment in vivo. Intriguingly, CCL5 expression was down-regulated in advanced patients (stage IIb-IV). The accumulation of CD8(+) T cells and CCR5(+)CD8(+) T cells was strongly reduced in advanced patients, suggesting that CCL5 expression may be involved in the local control of the disease and its reduction may be involved in disease progression.

CONCLUSIONSThe current data indicate the involvement of CCL5 in the regulation of CD8(+) T cell entry into tumor lesions in esophageal carcinoma patients. This process may affect the disease status and potentially as a prognostic factor for cancer patients. Enhancing local CCL5 expression in tumor lesions may represent a novel strategy in esophageal cancer therapy.

CD8-Positive T-Lymphocytes ; Chemokine CCL5 ; metabolism ; Disease Progression ; Esophageal Neoplasms ; metabolism ; Flow Cytometry ; Humans ; Leukocytes, Mononuclear ; Lymphocytes, Tumor-Infiltrating