| Esophageal carcinoma is one of malignant tumors with highest incidence in the world, and its incidence rate and mortality rate is the highest in China. It’s difficult to diagnose early esophageal cancer, the discovering and diagnosis of esophageal cancer occur only when patients exhibited clinical symptoms such as difficulty swallowing food in the esophageal cancer invasion or metastasis phase. Therefore, looking for new methods for early diagnosis and prognosis molecular markers for patients with esophageal cancer are very important and very urgent.DLK1(Delta drosophila homolog-like1or delta-like homologue), which is first found in neuroblastoma, DLK1protein is a member of the EGF family, it is a transmembrane protein, and is involved in regulating differentiation of virous cells. Currently, a large number of experiments confirmed DLK1is closely related to tumor development.Notch family is a highly conserved protein among the cell membrane membrane receptors, Notch signaling pathway is composed by the ligand, receptor and DNA binding protein, it maintains the balance between the cell proliferation, differentiation and apoptosis, regulates cell differentiation.It’s found that DLK1competitive combined with Notchl receptors in the Notch signaling pathway, plays a negative regulatory role. DLK1have a high homology with Notchl delta ligand. The N-terminal of DLK1does not have the domain section that is combined with Notchl, but its EGF-like extracellular domain interacted with Notchl, and the interaction part of Notchl receptor and DLK1is relatively unfixed.DLK1, Notchl joint detection expression in esophageal squamous carcinoma and its relationship with tumor have not been reported. This study use situ hybridization and immunohistochemical to detect expression of DLK1and Notchl in normal esophageal mucosa, adjacent atypical hyperplasia esophageal squamous cell carcinoma to study their correlation; we further use TUNEL Method to detect cell apoptosis in normal esophageal mucosa, adjacent atypical hyperplasia and esophageal squamous cell carcinoma. We use apoptotic index to reflect the degree of apoptosis, and we investigate the relation between esophageal squamous cell apoptosis and DLK1as well as the expression of Notchl.Methods1We use immunohistochemistry to detect the expression of DLK1protein and Notchl protein in62cases of normal esophageal mucosa,31cases of cancer tissue and62cases of esophageal squamous cell carcinoma.2We use in situ hybridization to detect the expression of DLK1mRNA and Notch1mRNA in62cases of normal esophageal mucosa,31cases of adjacent atypical hyperplasia and62cases of esophageal squamous cell carcinoma.3We use TUNEL Method to detect cell apoptosis in normal esophageal mucosa, adjacent atypical hyperplasia and esophageal squamous cell carcinoma. We investigate the relation between esophageal squamous cell apoptosis and DLK1as well as the expression of Notchl.4Statistical analysis:we use SPSS17.0software for statistical analysis, the correlation was significant when α=0.05.Results1DLK1protein and mRNA in esophageal squamous cell carcinoma tissues are strongly positive.The positive expression rate in ESCC is59.67%and48.38%. The positive expression rate in normal esophageal epithelium and adjacent atypical hyperplasia tissues are (0.00%,0.00%) and (3.22%,3.22%). The different expression of DLK1between ESCC and other groups was statistically significant (P<0.05), while there was no significant difference between adjacent atypical hyperplastic tissue and normal tissue (P>0.05).2Notchl protein and mRNA are strongly expressed in normal esophageal epithelium; otherwise, adjacent atypical hyperplasia and esophageal squamous cell carcinoma have a decreased expression. There was significant difference (P<0.05). Between ESCC group (positive rates were38.70%,30.64%) and the other two groups. And there was no significant difference between adjacent atypical hyperplastic tissue and normal tissue (P>0.05).3The expression of DLK1and Notchl was unconcerned with the gender, age and depth of invasion (P>0.05) of patients with esophageal squamous cell carcinoma, but they were associated with the patient’s histological grade and lymph node metastasis (P<0.05).4The protein expression of DLK1was negatively correlated with Notch l(P<0.05),and the expression of DLK1mRNA was negatively correlated with NotchlmRNA in esophageal squamous cell carcinoma (P<0.05).5Results of TUNEL method:compared to the other groups, the difference of esophageal squamous cell carcinoma was statistically significant (P<0.05). Apoptosis of tumor cells in esophageal squamous cell carcinoma was related to the expression of DLK1and Notchl. In the group which DLK1protein and Notchl protein positively express, tumor cells AI were (3.59±0.34)%and (3.50±0.38)%, lower than the negative expression group (4.47±0.36)%,(4.22±0.46)%, and the difference was statistically significant (P<0.01). Conclusion1The high expression of DLK1and lower expression Notchl are closely related with the occurrence and development of ESCC, and both may have antagonism in Occurrence and development of ESCC.2The high expression of DLK1and lower expression Notchl may participate in the apoptotic process of ESCC, and its mechanism needs further study. |
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