Expression And Biological Significance Of PPARγ In Esophageal Squamous Cell Carcinoma

Objectives:Esophageal cancer is one of the most common malignan-t tumor of the digestive system,claiming approximately300000deathsworldwide annually.Its morbidity and mortality rates vary in different co-untries.China,one of the high-incidence areas for esophageal cancer,is ho-me to50%of the deaths caused by esophageal cancer with a crude m-ortality rate of17.38/100000.Death toll of esophageal cancer in China a-ccounts for16.41%of the total cancer-related counterpart.Esophageal pa-thology is divided into Squamous cell carcinoma,Adenocarcinoma,Carcin-osarcoma,Sarcomatoid carcinoma and Small cell carcinoma.Squamous ce-ll carcinoma is the main in all of them,accounts for about90%of theincidence in China.Peroxisome proliferator-activated receptor proved to be a member ofthe nuclear receptor superfamily,it is a class with the DNA-respective e-lement bound ligand-activated transcription factors.Its main function is t-he specific regulation of the gene expression about growth and differentiation of cells.PPARγ is the most widely studied subtype in peroxisomeproliferator-activated receptors.Recent studies have confirmed that PPARγplay an important role in suppressing tumor cell proliferation,promotingcell differentiation,inducing apoptosis and inhibiting tumor angiogenesis i-n tumorigenesis and development.This experiment examine that PPARγ expressed in human esophagi-al carcinoma and far carcinoma（5cm above the edge away from the ca-ncerousexpression levels of tissues）using Immunohistochemistry and rea-l-time PCR,analysised its relationship with esophageal carcinoma clinicalpathological features,and explored the significance of its expression inesophageal squamous cell carcinoma.Provided a theoretical basis and exp -erimental evidence for the PPARγ agonist used in the clinical treatmentof cancer.Methods: Collected form February2013to December2013in Four-th Hospital of Hebei Medical University in thoracic surgery in patientswith esophageal squamous cell carcinoma,55cases of fresh tissue speci-mens,33cases of male patients,22cases of female patients,Male to fema-le ratio of1.5/1,the mean age of patients was62.3years.Among thesepatients,upper thoracic esophageal cancer6cases,32cases of carcinomaof the middle,under section17cases of cancer.Four cases of well-differentiated group,38cases of differentiated,13cases of poorly differentiated.They all have no radiation therapy and chemotherapy before surgery,andwere confirmed by pathology after surgery.At the same time selecting55patients′far carcinoma to corresponding fresh cancer tissue specimens（5cm above the edge away from the cancerous tissue) as a control gro-up.Patients were respectively recorded sex,age,histological type,degree ofdifferentiation,TNM staging and Lymph node metastasis.Selected histopa-thological wax block of55patients,and using Immunohistochemical met-hods to detected the expression of specimens PP-ARγ protein in the e-xperimental group and the control group. In addition,Using real-time qu-antitative PCR (RT-PCR),detected the expression levels of PPARγmRNAin the experimental group and a control group of specimens,then analysised its relationship with clinicopathological features of esophageal canc-er.Then analysised its relationship with clinicopathological features of es-ophageal cancer.Applying SPSS13.0statistical software for data analysis,using statistical analysis for the relationship between PPARγ protein andovarious clinical features of esophageal squamous cell carcinoma by ch-isquare test.Using the Wilcoxon signed-rank test analysis of the expression ofPPARγmRNA in esophageal tissue and far carcinoma tissue.Then,an-alysised the relationship between the PPARγ mRNA expression in esop-hageal cancer tissues and the clinical pathological features by Wilcoxonsigned-rank test or Kruskal-Wallis H test.P<0.05was considered statist -ically significant.Result:1Immunohistochemistry results1.1The expression of PPARγ protein in esophageal squamous cell carci-nomaThis group of experiment found that the expression of PPARγ prote-in is in the nucleus and/or cytoplasm,appear as brown or brownish yell-ow particles in the nucleus and/or cytoplasm is positive.PPARγ proteinhas low expression in esophageal cancer and high in far carcinoma tissu-es.The statistics of the experimental data show that the positive express-ion rate of PPARγ protein in esophageal squamous cell carcinoma is49.09%,and the far esophageal carcinoma positive expression rate is80.00%.The expression have difference between them,and the difference wasstatistically significant (P<0.05).1.2The relationship between PPAR protein expression and clinicopatholo-gical features in esophageal squamous cell carcinomaStudies have shown that the positive expression of PPARγ proteinwere27cases in all55cases of esophageal squamous cell carcinoma.T-he overall positive rate was49.09%.Distributed: male59.26%,female40.74%.Patients over60years of age including60-year-old59.26%,40.74%of patients under60years old patients.Tumor located in the upper eso-phagus is7.41%,Middle is62.96%,low segment is29.63%.Tumor with l-ow degree of differentiation is25.93%,differentiation is62.96%,well-diffe-rentiation is11.1%.Ⅰstage18.52%,Ⅱstage59.26%,Ⅲstage22.22%.Withoutlymph node metastasis is74.07%,and with lymph node metastasis is25.93%.Statistical analysis show that the PPAR protein expression have n-o relationship with gender, age, tumor location and lymph node metasta-sis. However,PPARγ protein expression have closely relationship with T-NM stage(χ2=13.713,P<0.05)and lymph node metastasis(χ2=13.245,P<0.05).2The test results of RT-PCR 2.1The expression of PPARγ mRNA in esophageal squamous cell carcinomaAble to detect the PPARγ mRNA in55cases of esophageal squamo-us cell carcinoma and its corresponding to far carcinoma tissues by RT-PCR.Compared with the far carcinoma tissues mucosa (3.32),PPARγmR-NA expression levels were significantly lower (1.00) in esophageal squa-mous cell carcinoma mucosa(P<0.05).1.2The relationship between the expression of PPARγ mRNA and Clini-copathological features in esophageal squamous cell carcinomaIn clinical pathology studies,PPARγ mRNA expression in esophagealsquamous cell carcinoma tissues has nothing to do with patients`age,ge-nder,and lymph node metastasis (P>0.05),but has correlated with the deg-ree of differentiation（P=0.007）,TNM stage（P=0.018）(P<0.05).Conclusion:1PPARγ protein in human esophageal squamous cell carcinoma was sig-nificantly reduced compared with far carcinoma tissues,and have closelyrelationship with the TNM stage and lymph node metastasis,but not wi-th sex and age,degree of differentiation of tumor and tumor site.PPARγprotein expression levels diminishing it with TNM stage;and without ly-mph node metastasis group was significantly higher than with lymph n-ode metastasis.2PPARγmRNA in human esophageal squamous cell carcinoma was sig-nificantly reduced compared with far carcinoma tissues,and have closelyrelationship with the TNM stage and degree of differentiation,but not wi-th sex and age,lymph node metastasis and tumor site.PPARγmRNA exp-ression levels diminishing it with TNM stage;and with diminishing degr-ee of differentiation is diminished.