Esophageal Squamous Carcinoma Tissues Research Articles

Landscape of epithelial cell subpopulations in the human esophageal squamous cell carcinoma microenvironment

AimsWe sought to reveal the landscape of epithelial cell subpopulations in the human esophageal squamous cell carcinoma microenvironment and investigate their parts on esophageal squamous carcinoma (ESCC) development. BackgroundEpithelial cells play an important role in the occurrence and development of ESCC through multiple mechanisms. While the landscape of epithelial cell subpopulations in ESCC, remains unclear. ObjectiveExploring the role of epithelial cell subpopulations in ESCC progression. MethodsSeurat R package was used for single-cell RNA sequencing (scRNA-seq) data filtering, dimensionality reduction, clustering and differentially expressed genes analysis. Cellmarker database was adopted for cell cluster annotation. Functional enrichment analysis was carried out by Gene Ontology (GO) analysis. InferCNV package was conducted for copy number variation (CNV) of epithelial cell subpopulations in all chromosomal regions. Pseudotime trajectory analysis was implemented for exploring differentiation trajectory of epithelial cells subgroups during the cancer progression. CellChat analysis was used for probing the interactions between epithelial cells and NK/T cells. cellular experiments were performed using Quantitative Real-Time Polymerase Chain Reaction (RT-qPCR), Wound-Healing Assay and transwell. Results11 major cell subpopulations were identified in ESCC and adjunct tissues. Further reclassification of epithelial cells uncovered 4 subpopulations. Enrichment analysis revealed that highly expressed genes in 4 epithelial cell subpopulations were related to cell proliferation, immune response and angiogenesis. CNV analysis found that UBD+ epithelial cells and GAS2L3+ epithelial cells had a higher proportion of CNV. Cell differentiation trajectories disclosed that KRT6C+ and GSTA1+ epithelial cells were in an intermediate state of differentiation, while UBD+ and GAS2L3+ epithelial cells are in an end state of differentiation during ESCC progression. Finally, we found that four epithelial cell subpopulations all inhibited NK/T cells through NECTIN2-TIGIT and CLEC2B-KLRB1. Low ATF3 and DDIT3 mRNA expression inhibited ESCC cell migration and invasion. ConclusionHere, we obtained a through epithelial cell atlas of ESCC at single-cell resolution, explored the role of epithelial cell in ESCC progression, and unveiled immunosuppressive signals to NK/T cells in promoting ESCC. Our findings expand the comprehension of epithelial cells and offer a theoretical guidance for future anti- epithelial cell treatment of ESCC.

COL8A1 Regulates Esophageal Squamous Carcinoma Proliferation and Invasion Through PI3K/AKT Pathway.

Esophageal squamous carcinoma (ESCC) is a gastrointestinal malignancy with a high mortality, but the tumorigenesis is still unclear, restricting the target therapy development of ESCC. We explored the role of COL8A1 in ESCC development. Tissue microarrays were used to investigate the expression level of COL8A1 in ESCC tissues. The association between COL8A1 and the overall survival of ESCC patients was assessed. The effect of differential COL8A1 expression on tumor growth was investigated by the xenograft model. The regulation of COL8A1 on tumor growth, migration, and invasion was studied by using ESCC cell lines. The signal transduction pathways involved in COL8A1 were bioinformatically profiled and validated. The COL8A1 was significantly expressed in cancerous tissues and was associated with poor prognosis in patients with ESCC. In vivo, the tumor growth obviously declined after inhibition of the COL8A1 expression. The abilities of cell proliferation and invasion were both decreased when the expression of COL8A1 was knockdown in ESCC cell line. Furthermore, we found the inactivation of the PI3K/AKT pathway that was mediated by knockdown of COL8A1 in ESCC cells, which was reversed with COL8A1 overexpression, whereas the cell proliferation and invasion ability were restored. This is the first report that COL8A1 promote ESCC progression, which hopefully will provide a theoretical basis for clinical targeting of ESCC.

Expression and Clinicopathological Significance of Extracellular Matrix Remodeling Markers in Esophageal Squamous Carcinoma.

Esophageal squamous cell carcinoma (ESCC) is a common malignancy of the gastrointestinal tract with a single therapeutic option and a lack of effective clinical therapeutic biomarkers. Extracellular matrix (ECM) remodeling plays a pro-carcinogenic role in a variety of malignancies, but its role in esophageal squamous carcinoma remains to be elucidated. In this study, we examined the expression levels of ECM remodeling markers in 71 pairs of esophageal squamous carcinoma tissues and normal tissues adjacent to the carcinoma using immunohistochemical staining, and analyzed their relationship with clinicopathological features and prognosis. The results suggested that extracellular matrix remodeling markers (integrin αV, fibronectin, MMP9) were abnormally highly expressed in esophageal squamous carcinoma tissues. There was a statistically significant difference between the positive expression of ECM remodeling and the TNM stage of esophageal squamous carcinoma, and there was no statistically significant correlation with age, gender and carcinoembryonic antigen expression, differentiation degree, T stage, and lymph node metastasis. Overall survival rate and overall survival time were significantly lower in patients with positive ECM remodeling expression, which was an independent risk factor for poor prognosisof esophageal squamous carcinoma.

TESC acts as a prognostic factor and promotes epithelial-mesenchymal transition progression in esophageal squamous carcinoma

BackgroundTescalcin (TESC) is a critical regulator of cell differentiation and growth, promoting malignant progression in various tumors. However, the role of TESC in esophageal squamous carcinoma (ESCC) remains unclear. MethodsImmunohistochemistry (IHC), quantitative real-time PCR (qRT-PCR), and western blot were utilized to identify the difference in TESC expression between ESCC tissues and normal tissues adjacent to the carcinoma. The relationship between TESC and several clinicopathological features was shown by the chi-square test. Log-rank analysis and Cox regression were used to detect the relationship between TESC and the prognosis in ESCC. Clone formation and cell count kit-8 (CCK-8) were applied to detect the impact of TESC on ESCC proliferation. Wound healing assay and transwell assay were used to confirm the influence of TESC on the invasion and migration. Spearman correlation coefficient was used to describe the correlation between TESC and epithelial-mesenchymal transition (EMT)-related protein expression in ESCC. Western blot was used to detect the effect of TESC on the expression of E-cadherin, N-cadherin, and Vimentin as well as AKT signaling pathway. Xenograft tumors were developed to test the pro-tumorigenic impacts of TESC in vivo. ResultsTESC was upregulated expression in ESCC tissues and was linked to poorer prognosis and worse tumor infiltration, TNM stage, and lymph node metastasis. Meanwhile, TESC was able to act as an independent prognostic factor in ESCC. TESC promoted tumor cell proliferation, invasion, migration, EMT progression, and activated the phosphorylation of the AKT pathway. Furthermore, TESC knockdown inhibited the growth of carcinoma in vivo. ConclusionTESC is a predictive factor for poor prognosis in ESCC and may provide a new strategy for ESCC treatment.

A novel protein encoded by circUBE4B promotes progression of esophageal squamous cell carcinoma by augmenting MAPK/ERK signaling

Esophageal squamous carcinoma (ESCC) is a common malignant cancer. Although the non-coding roles of circRNAs in the pathogenesis of human tumors have been well studied, whether circRNAs participate in the progression of ESCC by encoding novel proteins remains unclear. In this study, we identified an overexpression circRNA with protein-coding ability in ESCC tissues, called circUBE4B, whose expression level is correlated with tumor size and tumor differentiation level of ESCC patients. Moreover, a higher level of circUBE4B in ESCC patients is correlated with a worse prognosis. Functionally, we found that circUBE4B promoted the proliferation of ESCC cells by encoding a novel cancer-promoting protein, circUBE4B-173aa. Mechanistically, the circUBE4B-173aa protein interacts with MAPK1 and promotes the phosphorylation level of MAPK1 to eventually activate MAPK/ERK signaling pathway. The xenograft model revealed that overexpression of circUBE4B-173aa in ESCC cells significantly promoted the growth of grafts. Our study provides new insights into the mechanism of circRNA in the development of ESCC and circUBE4B-173aa has the potential to serve as a biomarker and a novel therapeutic target for ESCC therapy.

NIR-II Navigation with an EGFR-Targeted Probe Improves Imaging Resolution and Sensitivity of Detecting Micrometastases in Esophageal Squamous Cell Carcinoma Xenograft Models.

The survival rate of esophageal squamous carcinoma (ESCC) after surgical resection is estimated to be only 30.3% due to the difficulty in identifying microinfiltration and subtle metastases. In this study, we explored the value of near-infrared fluorescence in the second window (NIR-II) using an epidermal growth factor receptor (EGFR)-targeted probe (cetuximab-IR800) for the intraoperative navigation of ESCC in xenograft mouse models. Immunohistochemical results showed that EGFR was aberrantly expressed in 94.49% (120/127) of ESCC tissues and 90.63% (58/64) of metastatic lymph nodes. Western blot results demonstrated that EGFR protein was highly expressed in ESCC cell lines. Flow cytometry data revealed that cetuximab-IR800 showed a stronger binding specificity in EGFR-positive KYSE-30 cells than in A2780 control cells (P < 0.01). In vivo imaging data showed that the ratio of mean fluorescent intensity (MFI) and tumor to background (TBR) was significantly higher in KYSE-30 subcutaneous tumors with the infusion of cetuximab-IR800 than in those with the infusion of IgG1-IR800 (P < 0.05). Surgical navigation with NIR-II imaging showed that the TBR in orthotopic ESCC was significantly higher than that of NIR in the first window (NIR-I) (2.11 ± 0.46 vs 1.58 ± 0.31, P < 0.05), and NIR-II was more sensitive than NIR-I in detecting subcentimeter metastases (94.87% (37/39) vs 58.97% (23/39), P < 0.001). In conclusion, cetuximab-IR800 with high specificity for ESCC was first used in NIR-II surgical navigation. This probe showed better imaging resolution and higher sensitivity in detecting subtle metastases derived from an orthotopic ESCC model than NIR-I, which indicates that NIR-II has promise in guiding precise surgery for ESCC patients.

S479 Identification of Highly Expressed Genes in Esophageal Squamous Carcinoma Tissue: A Bioinformatical Analysis

S479 Identification of Highly Expressed Genes in Esophageal Squamous Carcinoma Tissue: A Bioinformatical Analysis

Telomerase inhibition decreases esophageal squamous carcinoma cell migration and invasion.

Telomerase has been shown to be associated with a variety of cancer types. To elucidate the role of telomerase in esophageal squamous carcinoma (ESCC), tissue samples from 100 patients with ESCC, and paired paracancerous tissues from 75 of these patients, were collected for use in the present study. Using immunohistochemical analysis, the expression of telomerase reverse transcriptase (hTERT) in the cytoplasm of ESCC cells was revealed to be significantly higher compared with that in paracancerous tissues, and no significant difference was observed between hTERT expression in the nucleus of ESCC and paracancerous tissue cells. Combined analysis revealed that the cytoplasmic hTERT-positive rate of patients with ESCC was significantly associated with pathological grade, N stage and Tumor-Node-Metastasis (TNM) stage; these data support the association between hTERT expression and poor patient prognosis. In vitro experiments demonstrated that hTERT knockdown does not inhibit the proliferation of ESCC Kyse410 or Kyse520 cells, but inhibits their migration and invasion abilities. These findings indicate that hTERT expression is associated with ESCC metastasis. Interestingly, decreased colony-formation ability was observed in Kyse410 cells, but not in Kyse520 cells. Collectively, the results of the present study suggest that hTERT may serve as a potential therapeutic target for ESCC.

The high expression of MTH1 and NUDT5 predict a poor survival and are associated with malignancy of esophageal squamous cell carcinoma.

BackgroundMTH1 and NUDT5 effectively degrade nucleotides containing 8-oxoguanine. MTH1 and NUDT5 have been linked to the malignancy of multiple cancers. However, their functions in tumor growth and metastasis in esophageal squamous carcinoma (ESCC) remain obscure. Our present study aims to explore their prognostic value in ESCC and investigate their function in MTH1 or NUDT5-knockout tumor cells.MethodsMTH1 and NUDT5 protein expression in ESCC adjacent normal tissues and tumor tissues was examined by immunohistochemistry staining. Kaplan–Meier curves were used to assess the association between their expression and overall survival (OS) in ESCC patients. Univariate and Multivariate Cox regression analyses were generated to determine the correlation between these protein expression and OS of ESCC patients. Protein expression in ESCC cell lines were measured by Western blotting. To explore the potential effects of the MTH1 and NUDT5 protein in ESCC, cell models with MTH1 or NUDT5 depletion were established. CCK-8, cell cycle, Western blotting, migration and invasion assays were performed.ResultsOur present study demonstrated that the levels of MTH1 and NUDT5 were upregulated in ESCC cell lines and ESCC tissues, the expression of MTH1 and NUDT5 in ESCC tissues was significantly higher than in adjacent non-tumorous, and higher levels of MTH1 and NUDT5 predicted a worse prognosis in patients with ESCC. MTH1 and NUDT5 are novel biomarkers of the progression of ESCC and a poor prognosis. We also found for the first time that the high expression of NUDT5 independently predicted lower OS in patients with ESCC (hazard ratio (HR) 1.751; 95% confidence interval (CI) [1.056–2.903]; p = 0.030). In addition, the depletion of MTH1 and NUDT5 strongly suppressed the proliferation of ESCC cells and significantly delayed the G1 phase of the cell cycle. Furthermore, we found that MTH1 and NUDT5 silencing inhibited epithelial–mesenchymal transition mainly by the MAPK/MEK/ERK dependent pathway, which in turn significantly decreased the cell migration and invasion of ESCC cells. Our results suggested that the overexpression of MTH1 and NUDT5 is probably involved in the tumor development and poor prognosis of ESCC.

Fbxw8 protein promotes the proliferation and metastasis of ESCC

Objective: This article plans to investigate Fbxw8 protein expression in esophageal squamous cell carcinoma tissues. And its effect on the proliferation ability of esophageal squamous cancer KYSE70 cells is analyzed. Methods: We can detect Fbxw8 protein expression in esophageal squamous cell carcinoma tissues with IHC and analysis the expression with the sex, age, lymph node metastasis and tumor stage. We alsodetect the proliferation of KYSE70 cells with CCK 8. Result: Most esophageal squamous carcinoma tissues highly expressed Fbxw8 protein, and the expression was positively correlated with lymph node metastasis and tumor staging (P &lt; 0.05). Fbxw8 siRNAs can significantly cut FBXW8 protein expression, while lowering the cell cycle related protein expression of Cyclin A, Cyclin B1, and inhibiting KYSE70 cell proliferation. Conclusion: Fbxw8 protein highly expressed in esophageal squamous carcinoma tissues, and closely related to tumor staging. Targeted inhibition Fbxw8 protein expression could significantly inhibit the proliferation of esophageal squamous carcinoma cells.

Changing expression profiles of lncRNAs, circRNAs and mRNAs in esophageal squamous carcinoma.

Abundant evidence indicates that long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs) serve important roles in tumorigenesis and tumour progression. However, their diagnostic and treatment value for esophageal squamous carcinoma (ESCC) remains unknown. A microarray (SBC human ceRNA array V1.0) was performed to assess the expression profiles and biological functions of lncRNAs, circRNAs and mRNAs in ESCC and para-cancerous tissues from three patients. Microarray data were validated by reverse transcription-quantitative polymerase chain reaction for a group of genes. A number of lncRNA-microRNAs (miRNA) and circRNA-miRNA-mRNA networks were constructed. Bioinformatics tools, including gene ontology and Kyoto Encyclopedia of Genes and Genomes biological pathway analyses, were used to predict the functions of differentially expressed lncRNAs, circRNAs and potentially co-expressed target genes. The results revealed that compared with the expression levels of para-cancerous tissues, 1,384 lncRNAs, 2,046 circRNAs and 936 mRNAs were frequently altered in ESCC tissues. Co-expression networks of lncRNAs-miRNAs-circRNAs-mRNAs were constructed based on the correlation analyses among the differentially expressed RNAs. Furthermore, using bioinformatics methods, correlation expression networks were constructed that included cis- and trans-regulatory elements. Therefore, these results suggest that lncRNAs and circRNAs may be involved in the pathogenesis and development of ESCC. These findings provide a novel and systematic perspective on the potential function of noncoding RNAs in ESCC.

Relationship between expression of genes associated with retinoid interferon induced mortality-19, signal transducer and activators of transcription 3, and myeloid cell leukemia-1 with proliferation and apoptosis of esophageal squamous carcinoma cells

Objective To investigate the relationship between the expression of genes associated with retinoid interferon induced mortality-19 (GRIM-19), signal transducer and activators of transcription 3 (STAT3), and myeloid cell leukemia-1 (Mcl-1) with esophageal squamous carcinoma cells proliferation and apoptosis and the possible mechanism. Methods The protein expression of GRIM-19, STAT3, Mcl-1 and proliferation cell nuclear antigen (Ki-67) in 50 cases of esophageal squamous carcinoma tissues, 30 cases of atypical tissue adjacent to carcinoma and 50 cases of normal esophageal mucosa tissues was detected by immunohistochemical streptavidin avidin-peroxidase (SP) method. The mRNA expression of GRIM-19, STAT3, Mcl-1 and Ki-67 in 50 cases of esophageal squamous carcinoma tissues, 30 cases of atypical tissue adjacent to carcinoma and 50 cases of normal esophageal mucosa tissues was detected by in situ hybridization. TdT-mediated deoxyuridine triphosphate (dUTP) nick end labeling (TUNEL) method was applied to examine apoptosis of esophageal squamous carcinoma cells. Results The positive expression rate of GRIM-19 protein and mRNA in esophageal squamous carcinoma tissues was significantly lower than that in atypical hyperplasia tissue adjacent to carcinoma and normal esophageal mucosa (protein: χ2=12.130, P=0.000; mRNA: χ2=11.830, P=0.000). The positive expression rate of STAT3 and Mcl-1 protein and mRNA in esophageal squamous carcinoma tissues was significantly higher than that in atypical hyperplasia tissue adjacent to carcinoma and normal esophageal mucosa (STAT3 protein: χ2=4.910, P=0.000, STAT3 mRNA: χ2=5.410, P=0.000; Mcl-1 protein: χ2=4.970, P=0.000, Mcl-1 mRNA: χ2=5.370, P=0.000). The apoptosis of tumor cells in esophageal squamous carcinoma tissues was associated with the positive expression rate of GRIM-19, STAT3 and Mcl-1. The apoptosis index (AI) in the group of GRIM-19 positive expression was higher than that in the group of GRIM-19 negative expression (F=18.355, P=0.048). The AI in the group of STAT3 positive expression was lower than that in the group of STAT3 negative expression (F=19.003, P=0.036). The AI in the group of Mcl-1 positive expression was lower than that in the group of Mcl-1 negative expression (F=18.225, P=0.044). Conclusion The down-regulation of GRIM-19, and up-regulation of STAT3 and Mcl-1 may promote esophageal squamous cancer cell proliferation, and inhibit esophageal squamous cancer cell apoptosis. Key words: Genes associated with retinoid interferon induced mortality-19; Signal transducer and activators of transcription 3; Myeloid cell leukemia-1; Esophageal squamous carcinoma cells; Apoptosis

Expression of annexin A1 protein in esophageal carcinoma and its clinical significance

Objective To investigate the biological role of Annexin A1 protein in carcinogenesis and progression of esophageal carcinoma. Methods Annexin A1 protein level was analyzed by immunohistochemical assay in 94 cases of esophageal squamous carcinoma tissues and surrounding normal tissues. Annexin A1 overexpression and knockdown stable cell lines in human immortalized esophageal epithelial cell line SHEE were constructed by lentivirus. Cell proliferation of Annexin A1 overexpression and knockdown stable cell lines were analyzed by cell counting kit-8 (CCK-8). Cell invasion ability of Annexin A1 overexpression and knockdown stable cell lines were analyzed by transwell method. Cell colony forming ability in stable cell lines was analyzed by soft agar assay. Tumor formation in mice was analyzed by cell transplantation. Results Compared with the normal esophageal tissues, the expression levels of Annexin A1 protein in esophageal cancer tissues increased significantly (P=0.004). Compared with the control cell lines, proliferation (P=0.026) and invasion (P=0.017) ability in Annexin A1 protein overexpression cell lines significantly increased, while in the Annexin A1 protein knockdown cell lines, cell proliferation (P=0.019) and invasion (P=0.023) ability significantly decreased. Compared with the control cell lines, the clonal formation ability of Annexin A1 overexpression cell lines significantly enhanced(P=0.022), while the ability of clones formation in Annexin A1 protein knockdown cell line significantly decreased (P=0.035). In vivo tumor formation test showed that the tumor formation rate in Annexin A1 protein overexpressing cell lines significantly increased compared with control cell lines (P=0.001). Conclusion Annexin A1 protein overexpressed in esophageal carcinoma tissues, which was involved in the growth, invasion and tumorigenesis of esophageal cancer cells. Key words: Annexin A1 protein; Esophageal carcinoma; Proliferation; Invasion; Tumorigenesis

Direct Downregulation of B-Cell Translocation Gene 3 by microRNA-93 Is Required for Desensitizing Esophageal Cancer to Radiotherapy.

Esophageal squamous carcinoma (ESC) is one of the most fatal malignancies worldwide with increasing occurrences yet poor outcome. MicroRNAs were reported to play roles in ESC. We aimed to understand how miRNAs affect the radiotherapy resistance of ESC. MicroRNA assays, real-time PCR, and Western blot were performed for expression analysis of miR-93 and BTG3. Luciferase activity assay was conducted with mutated B-cell translocation gene 3 (BTG3) 3'-UTR sequence in the 3' end of luciferase sequence with miR-93 inhibitor. ESC cells were treated with irradiation (IR) and clonogenic assay was utilized to detect the cell viability. Human ESC xenograft mouse model was established and subjected to target IR treatment followed by tumor size analysis. MiR-93 was decreased and BTG3 was increased in ESC cells, with negative correlation of their expression in ESC tissues. MiR-93 directly targeted BTG3 3'-UTR by luciferase activity assay. Either miR-93 inhibition or BTG3 overexpression decreased radiation resistance. Furthermore, miR-93 inhibition suppressed radiation resistance through BTG3. Direct downregulation of BTG3 by miR-93 is able to render ESC resistant to radiotherapy, and both BTG3 and miR-93 may potentially serve as clinical markers for ESC and contribute to the treatment of ESC.

Clinical significance of the expression of eukaryotic initiation factor 4 E and mammalian target of rapamycin in esophageal squamous carcinoma tissues

To explore the clinical significance of eukaryotic initiation factor 4 E (eIF4E) and mammalian target of rapamycin (mTOR) expressions in esophageal squamous carcinoma tissues. Clinicopathological data and paraffin samples of resected tumor tissue from 148 patients with esophageal squamous carcinoma undergoing resection in our department between January 2010 and December 2012 were collected retrospectively. Expressions of eIF4E and mTOR were detected in above carcinoma tissues, counterpart para-carcinoma tissues (1 cm distance to carcinoma) and normal tissues (5 cm distance to carcinoma) with Western blot and immunohistochemistry. Their relevance with clinicopathological features was analyzed. Expression of mTOR located mainly in cytoplasm and elF4E mainly in cellular membrane, presenting as yellow grains. These two markers showed strong expression in carcinoma tissues and weak or none in para-carcinoma tissues. In esophageal squamous carcinoma tissues, counterpart para-carcinoma tissues and normal tissues, mTOR protein expression was 85.8% (127/148), 35.1% (52/148) and 3.4% (5/148), eIF4E protein expression was 93.9% (139/148), 35.1% (52/148) and 12.8% (19/148), with a downtrend respectively (all P<0.05). Expressions of mTOR and eIF4E were associated with tumor invasion depth and lymphatic metastasis (all P<0.05), while mTOR expression was associated with differentiation degree (P=0.003), but eIF4E expression was not. Both expressions were not associated with gender, age, and tumor size (all P>0.05). Expressions of eIF4E and mTOR are up-regulated in esophageal squamous carcinoma tissues, which may be associated with tumor malignance and lymphatic metastasis of esophageal squamous carcinoma. Combined detection of two markers may be helpful to predict the tumor malignance and the prognosis of patients.

Expression of elastic fiber in esophageal squamous carcinoma tissue.

We studied the expression of elastic fiber in esophageal squamous cell carcinoma tissue in North-eastern Indian population. Archival paraffin embedded 40 esophageal carcinoma specimens were retrieved for the study. Only smokers were included in the study. Verhoeff's stain for elastic fiber was performed to demonstrate elastic fiber with positive and negative control. A total of 28 (70%) tissue specimens was found to be positive for elastic fiber. Elastosis in esophageal carcinoma may be due to smoking. Further studies are required to rule out the etiology.

Expression and clinical significance of DAPK1 and CD147 in esophageal squamous cell carcinoma

To explore the amplification and expression status of DAPK1 and CD147 in esophageal squamous cell carcinoma (ESCC) and their relationship with the prognosis of ESCC. Immunohistochemical staining and RT-PCR were used to detect the expression and amplification of DAPK1 and CD147 in esophageal squamous carcinoma tissue and normal esophageal mucosa. Statistical analysis of the clinocopathological data was performed with SPSS 11.5 software package. The positive rates of expression of DAPK1 protein and CD147 protein in the specimens of esophageal carcinoma were 31.3% and 58.5%, and in normal esophageal mucosa 57.5% and 25.0%, respectively, with a statistically significant difference (P < 0.001). The expressions of DAPK1 and CD147 were significant correlated with invasion depth, lymph node metastasis, TNM stage and the degree of cancer differentiation. (P < 0.05). The negative expression of DAPK1 and positive expression of CD147 indicated a poor prognosis. In 52 ESCC cases, the expression of DAPK1 in cancer tissues was 0.236 ± 0.049, and 0.395 ± 0.058 in normal esophageal mucosa, while that of CD147 mRNA expression was 0.942 ± 0.204 and 0.821 ± 171, respectively, statistically both with a very significant difference (P < 0.01). There was a higher expression level of DAPK1 mRNA in the cancer tissue in patients with no lymph node metastasis, well differentiation, and earlier pathological stage, and a higher expression level of CD147 mRNA in the cancer tissues in patients with lymph node metastasis, poor differentiation, and later pathological stage. The expression of DAPK1 and CD147 proteins is closely correlated with the clinicopathological characteristics of ESCC. The genes DAPK1 and CD147 may participate in the metastasis and apoptosis of ESCC. The expression of DAPK1 and CD147 may be used as important prognostic predictors in ESCC.

Analysis of HER2 gene amplification and protein expression in esophageal squamous cell carcinoma

The HER2 gene, which is located on chromosomes 17, is a therapeutic target for cancer. Amplification of HER2 has been described in several tumor types. However, few studies of HER2 gene amplification and protein expression in esophageal carcinoma have been conducted. This study was to investigate the relationship between the expression of HER2/neu and the clinical characteristics, including survival rate, of esophageal squamous carcinoma. The clinical data of 145 patients admitted in Renmin Hospital of Wuhan University, from 2000 to 2005, were reviewed. The HER2 protein expression and gene status in 145 esophageal carcinomas were evaluated using immunohistochemistry and fluorescence in situ hybridization. The survival rate was calculated by the Kaplan-Meier method and the log-rank test using SPSS13.0 software. Compared to normal esophageal epithelium (23/95, 24.2%), HER2 protein was overexpressed in most esophageal squamous carcinoma tissues (60/145, 41.4%), of which 45 (31.0%) were 2+ and 15 (10.4%) were 3+, HER2 overexpression associated significantly with HER2 gene amplification. There is a correlation between the overexpression of HER2 and the differentiation of the carcinoma, the HER2 gene amplification and the differentiation of the carcinoma and the tumor stage. According to univariate analysis, there was a significant difference in survival rates when cases with and without HER-2/neu overexpression or amplification were compared. HER-2/neu amplification/overexpression may be used as an independent prognostic factor in patients with esophageal squamous cancer, and patients with HER-2/neu amplification/overexpression might be potential candidates for new adjuvant therapies that involve the use of humanized monoclonal antibodies.

Expression of vascular endothelial growth factor-C and its receptor in esophageal squamous carcinoma tissues and its clinical significance

Expression of vascular endothelial growth factor-C and its receptor in esophageal squamous carcinoma tissues and its clinical significance

Expression of Ras-GTPase-activating protein SH 3 domain binding protein and osteopontin in esophageal squamous carcinoma and their effects on prognosis

To investigate the expressions and significances of Ras-GTPase-activating protein SH 3 domain binding protein(G3BP) and osteopontin (OPN) proteins in esophageal squamous carcinoma (ESC). The expressions of G3BP and OPN proteins in 80 cases of ESC were detected by immunohistochemistry. The relationships between the 2 protein expression and tumor size, differentiation degree, TNM stage, lymph node metastasis and prognosis of ESC were also explored. (1) The positive expression rate of G3BP in ESC was 71.3%, and the rate in lymphoid metastatic group was significantly higher than that in non lymphoid metastatic group (Z=-2.283, P=0.022), but no relations were found between G3BP expression and diameter of tumor, differentiation and TNM grade (P>0.05). The G3BP positive expression group had shorter survival time than G3BP negative expression group (P=0.000). (2) The positive expression rate of OPN in ESC was 100%, and the degree of OPN expression was correlated with the differentiation (chi(2)=10.766, P=0.005) and lymphoid metastasis (Z=-2.289, P=0.022), but no relationship was found between the diameter of tumor and TNM grade (P>0.05). The expression of OPN were significantly related to survivals in a negative time-dependent manner in ESC patients (P=0.000). (3) The expression of G3BP protein correlated positively with the degree of OPN expression in ESC tissue (r(s)=0.376, P=0.001). The expressions of G3BP and OPN proteins have a close relationship with lymphoid metastasis and survival in ESC patients. G3BP and OPN proteins can be considered as predictors of prognosis in ESC patients.