| Background and objectiveCurrently on a global scale,the appearance of digestive tract malignancy is more and more frequent and severe,thereinto,esophageal cancer is one of the most serious malignancy which has high morbidity and mortality,and endangering people’s health in a large extent.China,as the region of high incidence of esophageal cancer in the world,is facing a growing prevalence of esophageal cancer,which is about 10 cases in 100,000 people,especially in Hebei(the surrounding area of Taihang mountain),and Linzhou,Huixian,Anyang city in Henan province.The histological types of esophageal cancer are mainly squamous cell carcinoma and adenocarcinoma,but of most patients in China,the main type is squamous cell carcinoma,and the type of adenocarcinoma only accounts for about a small part.Anatomical site of esophageal cancer is relatively special,so it is very hard to make a early diagnosis of esophageal cancer.Patients usually go to see a doctor only when symptoms of esophageal cancer attack and become serious,therefore,the incidence is about equal to death.If we can give the diagnosis and therapy at the time of the early pathological changest,it will be of great benefit to screen high-risk patients and improve the survival rate.There are many reasons for the pathogenesis of esophageal cancersuch as genetic and environmental factors,however,it remains unclear.With increasingly development of molecular biology,people gradually realized that the occurrence and development of tumor is a complex process of multiple factors.There are more and more researches on the clinical and pathological features of esophageal cancer,but there are still no predictive factors.In recent years,many studies have shown that in addition to oncogenes and tumor suppressor genes which can regulate the malignant transformation,cell cycle regulation proteins and their receptors such as cyclin dependent kinas,can activate the cell signal transduction pathways and stimulate the key function of the cell cycle in order to play an important role in cell growth,proliferation and differentiation.Among them,as the cell cycle protein kinase(cyclin dependent kinase,CDK),CDK14(PFTK1)is relatively new and rarely researched.There are studies found that PFTK1/CyclinY can phosphorylated LDL receptor related protein(low density lipoprotein receptor-related protein,LRP)5 and 6,therefore,LRP5 and LRP6 can combine with Wnt protein and play its regulative role as auxiliary receptor of extracellular signals.It has been reported as a regulation factor to participate in the development of liver cancer,however,its expression in esophageal squamous carcinoma has not been reported.Pang et al have found that the expression of PFTK1 was closely associated with late tumor metastasis and microvascular invasion.As a member of vascular endothelial growth factor(VEGF)family,VEGF-C is the most important controller of lymphatic generated signaling pathways,and it can induce the formation of blood vessels and lymphatic vessels,and also promote tumor cells of lymph node metastasis.However,its role in esophageal squamous carcinoma,lymph node metastasis and prognosis is still not sure,also,its relation with PFTK1 has not yet been reported.In this study,we detected the expression of PFTK1、LRP5、LRP6 and VEGF-C protein usingin situ hybridization and immunohistochemical SP method respectively,and our aim is to clarify their influences on the occurrence,development,invasion and metastasis of esophageal squamous carcinoma,and also their relationship.Material and methods1.We choosed 53 Esophageal squamous cell carcinoma,25 normal esophageal mucosa and 21 adjacent atypical hyperplasia tissues using immunohistochemical staining to measure the protein expression of PFTK1,LRP5,LRP6 and VEGF-C.2.To detect the mRNA expression of PFTK1,LRP5,LRP6 and VEGF-C in 53 Esophageal squamous cell carcinoma,25 normal esophageal mucosa and 21 adjacent atypical hyperplasia tissues using in situ hybridization method.3.SPSS(version 20.0)was carried out to statistical analysis.We used Chi-square test to compare the positive rate.Data does not meet the requirements for the chi-square analysis,Fisher’s exact probability method is used.Result1.The mRNA and protein expression of PFTK1 was positively correlated with the expression of LRP5,LRP6 and VEGF-C in esophageal squamous carcinoma tissues(P< 0.05).2.The mRNA and protein positive expression rate of PFTK1 in esophageal squamous carcinoma tissues is higher than adjacent carcinoma and normal esophageal mucosa tissues.The mRNA positive rate were 4.0%(1/25)、 38.1%(8/21)、 83%(44/53).The three comparative differences statistically significant(P < 0.05),the protein positive rate were 8.0%(2/25)、 38.1%(8/21)、 71.7%(38/53),the three comparative differences statistically significant(P < 0.05).The mRNA and protein positive expression rate of PFTK1 is positively correlated with infiltration depth,histological grading,and lymph node metastasis(P< 0.05),however,it has nothing to do with the patient’s age and sex(P> 0.05).3.The mRNA and protein positive expression rate of LRP5 in esophageal squamous carcinoma tissues is higher than adjacent carcinoma and normal esophageal mucosa tissues,The mRNA positive rate were 8.0%(2/25)、 23.8%(5/21)、75.4%(40/53),the three comparative differences statistically significant(P < 0.05),the protein positive rate were 12%(3/25)、38%(8/21)、74.8%(39/53),the three comparative differences statistically significant(P < 0.05).The mRNA and protein positive expression rate of LRP5 is positively correlated with infiltration depth,histological grading,and lymph node metastasis(P< 0.05),however,it has nothing to do with the patient’s age and sex(P> 0.05).4.The mRNA and protein positive expression rate of LRP6 in esophageal squamous carcinoma tissues is higher than adjacent carcinoma and normal esophageal mucosa tissues,The mRNA positive rate were 0%(0/25)、 47.6%(10/21)、79.2%(42/53),the three comparative differences statistically significant(P < 0.05),the protein positive rate were 19%(4/25)、42.8%(9/21)、69.8%(37/53),the three comparative differences statistically significant(P < 0.05).The mRNA and protein positive expression rate of LRP6 is positively correlated with infiltration depth,histological grading,and lymph node metastasis(P< 0.05),however,it has nothing to do with the patient’s age and sex(P> 0.05).5.The mRNA and protein positive expression rate of VEGF-C in esophageal squamous carcinoma tissues is higher than adjacent carcinoma and normal esophageal mucosa tissues,The mRNA positive rate were 4.0%(1/24)、 19%(4/21)、 62.3%(33/53),the three comparative differences statistically significant(P < 0.05),the protein positive rate were 0%(0/25)、23.8%(5/21)、69.8%(37/53),the three comparative differences statistically significant(P < 0.05).The mRNA and protein positive expression rate of VEGF-C is positively correlated with infiltration depth,histological grading,and lymph node metastasis(P< 0.05),however,it has nothing to do with the patient’s age and sex(P> 0.05).Conclusion1.The mRNA and protein expression of PFTK1、LRP5、LRP6 and VEGF-C were increased significantly in esophageal squamous carcinoma tissues,which indicate thatPFTK1、LRP5、LRP6 and VEGF-C may participate in the development of esophageal squamous carcinoma.2.The expression of PFTK1 was positively correlated with the expression of LRP5,LRP6 and VEGF-C in esophageal squamous carcinoma,which indicate that PFTK1 may regulate the expression of LRP5、LRP6 and VEGF-C in esophageal squamous carcinoma through Wnt signal pathway. |
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