| ObjectivesLung cancer is one of the most common deadly cancers in malignant tumors.It is characterized by excessive proliferation,high degree of malignancy,invasion and metastasis,and drug resistance.According to the traditional theory,the occurrence of tumor is mainly due to the qualitative change of normal cells in the body under the action of many internal causes(including heredity,endocrine,etc.)and many external causes(physical,chemical,biological,etc.),so as to have the ability of excessive proliferation.Therefore,the treatment of malignant tumor is mainly targeted at the tumor cells themselves,so the corresponding treatment methods are mainly surgery,radiotherapy,cryoablation and to remove local tumor tissues.For the invasion of lung cancer tumor cells,platinum based two-drug systemic chemotherapy is mainly adopted.Surgical treatment requires a high level of cardiopulmonary function.Even if radical resection is performed,tumor recurrence and metastasis cannot be avoided.Radiation therapy,cryoablation,thermal ablation and chemotherapy all had great damage to normal cell function.With the development of molecular biology and the application of targeted therapy,anti-vascular tumor drug therapy and pd-11 immunotherapy through gene detection,the survival time of lung cancer patients has not been improved.A growing number of studies found that the progress of the tumor is not only related to tumor cells themselves,are also associated with tumor cells surrounding microenvironment,main composition in the microenvironment of fibroblasts as main ingredients,extracellular matrix cells participating in tumor mainly in activation state evolution process,the active state is called cancer associated fibroblasts(carcinoma-associated fibroblasts,CAFs).Compared with normal fibroblasts(NFs)in normal tissues,the expression of interstitial protein increased,the content of lactic acid increased through glycolysis to strengthen the energy supply of tumor cells,participate in tumor angiogenesis,promote tumor invasion and metastasis,and even be related to tumor drug resistance and recurrence.Therefore,CAFs as a new therapeutic target is of breakthrough significance for tumor therapy.Fibroblast activation protein(Fibroblast activation protein,FAP)is a type II transmembrane serine proteolytic enzyme,in primary lung cancer,esophageal cancer,liver cancer,breast cancer and colorectal cancer and other solid tumors in selective expression in CAFs,except in embryonic organization,FAP barely exist in normal tissue,and studies have confirmed that the expression of FAP is closely relative to the degree of infiltration,lymph node metastasis of lung cancer,negative correlation with prognosis.This makes FAP a potential specific target for tumor therapy.Podoplanin(PDPN)is a type 1 transmembrane sialate glycoprotein consisting of an extracellular domain,a single transmembrane portion,and a short cytoplasmic tail for phosphorylation of protein kinase C and cAMP.In the past,PDPN has been widely used as a specific marker for lymphatic endothelium in histopathology.Recent studies have also confirmed the expression of CAFs in lung adenocarcinoma,but the specific gene mechanism and target therapy have not been clarified.Therefore,in this study,the lung adenocarcinoma and adjacent tissues were first obtained,and the expression of FAP protein and PDPN protein in CAFs was measured by immunohistochemistry,so as to observe the effect of FAP and PDPN on lymph node metastasis of lung adenocarcinoma.The interaction between CAFs and tumor cells was analyzed to provide a feasible theoretical basis for finding new therapeutic methods for tumors.Materials and methodsA total of 141 patients who were first diagnosed and underwent radical lung cancer resection at shandong university's shandong provincial hospital on December,2014 were selected.The screening criteria were pulmonary adenocarcinoma with nodules less than or equal to 3cm and confirmed by postoperative pathology.The expression of FAP protein and PDPN protein in CAFs was detected by immunohistochemical staining in 141 samples.The samples with 4%PBS buffer were used as the control group to analyze the differences in the expression of FAP and PDPN in CAFs and NFs,as well as the relationship with lymph node metastasis.The relationship between FAP and PDPN and clinical prognosis was analyzed with clinical case data.Results1.Lung adenocarcinoma and adjacent tissue slides were successfully preparedUnder the microscope,CAFs were observed in a long spindle shape.Compared with NFs,the shape of CAFs was not uniform.2.FAP and PDPN promoted the infiltration and metastasis of lung adenocarcinoma cells and were associated with poor prognosis of lung cancerThe results of immunohistochemical staining in this study showed that PDPN protein was only expressed in lung invasive adenocarcinoma,and the expression of FAP and PDPN in lung adenocarcinoma CAFs was significantly higher than that in NFs tissues,and was positively correlated with lymph node metastasis and clinical stage.3.The positive expression of FAP was positively correlated with the positive expression of PDPN.Conclusion1.The expression of FAP protein and PDPN protein in CAFs of lung adenocarcinoma was higher than that in normal lung tissues,and PDPN was only highly expressed in lung invasive adenocarcinoma,suggesting that FAP protein and PDPN protein were related to the occurrence of lung adenocarcinoma.2.FAP protein and PDPN protein are related to clinical stage and lymph node metastasis of lung adenocarcinoma;There was no significant relationship with age,smoking and positive edge.It can be used as a specific index to predict the prognosis of lung cancer3.FAP protein was positively correlated with PDPN protein expression in lung invasive adenocarcinoma.It may be used as a co-indicator to predict the progression of lung cancer. |
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