Expression Of ADM, IMD, HUⅡ, URP And Their Receptors In Tissues Of Non-small Cell Lung Cancer Patients And Its Clinical Significance

Background and Objective:Lung cancer has become the highest incidence and mortality neoplastic diseases. Non-smallcell lung cancer (Non small cell lung cancer of NSCLC) accounts for about80%of all lungcancer, The majority of patients diagnosed at the late phase of disease, lost the best time ofsurgery, radiotherapy and chemotherapy. With the development of the molecular biology inrecent years, molecular targeted therapy for NSCLC. Provide a new therapeutic approach foradvanced NSCLC. However, genetic, environmental, and immune factors all can contribute tothe development of NSCLC, in which varies biological activities such as Tumor angiogenesisand cell proliferation can be participated. The efficiency of Molecular targeted drugs used in inclinical is still low. To research the pathogenesis of NSCLC is of great significance for the earlydiagnosis and effective treatment of NSCLC.Adrenomedullin (ADM), Intermedin(IMD), human Urotensin-II (hU II), urotensin-relatedpeptide (URP) are all small molecular bioactive peptides. They can expressed in a variety oftissues and organs in the body, and displayed a variety of biological functions. ADM and IMDwhich all belong to the calcitonin gene-related peptide family, are powerful vasodilators. ADMcould protect myocardial cells of oxygen in heart failure; the IMD can play a more prominentrole in the regulation of renal blood flow. hU II and URP are all belong to the somatostatinfamily. The hU II which is considered to be the most powerful vasoconstrictor substances everdiscovered, can take part in the pathophysiology of myocardial remodeling process. URP canregulate the activities of the central nervous system. The study found that abnormal expression ofADM, hU II, and its receptor can be detected in a variety of tumor cells in vitro and tumors inhuman bodys. Many researches show that ADM, hU II can stimulate the growth of tumorangiogenesis, proliferate the tumor cell. The research of the relationship between IMD, URP andthe tumor is less. We can only learn that IMD is highly expressed in adrenal cortical carcinoma,melanoma and other solid tumors; URP can be expressed in the pulmonary lymphangioma. Ourgroup have found that the expression of ADM IMD and hU II were higher in plasma and tissueof patients with lung cancer by the method of radioimmunoassay and immunohistochemical. Tofurther investigate the role of ADM IMD hU II and URP in the development of NSCLC, we determine the expression levels of ADM IMD hU II URP and its receptors Calcitonin receptorlike receptor(CRLR), Receptor activity modifying protein1-3(RAMP1-3), Urotensin-II receptor(UT) in cancer tissues and adjacent tissues of patients with NSCLC, Analysis the relationship ofthe expression levels of ADM, IMD, hU II and URP in patients with NSCLC betweenpathological types, TNM (Tumor Node metastasis the TNM) stages, distant metastasis. Analysisthe situation of the distribution of the different receptors of ADM, IMD, hU II and URP incancer tissues and adjacent tissues. To further investigate the role of ADM, IMD, hU II and URPin the development process of NSCLC.Methods:Collection the fresh cancer tissue and adjacent noncancerous tissue samples of27cases ofNSCLC who take the surgerys, and their clinical datas. Designing primers and using real timequantitative PCR method to detect the mRNA expression of ADM, IMD, hU II, URP and relatedreceptors of CRLR, of RAMP1, RAMP2, RAMP3, UT in tissue samples.Results:1.ADM and its receptors were higher expressed in cancer tissues of NSCLC than theadjacent tissues, the expression levels of ADM in distant metastasis were higher than thosewithout metastasis patients, the difference was statistically significant (P<0.05).2. IMD and its receptors were higher expressed in cancer tissues of NSCLC than theadjacent tissues, the expression of IMD in patients with-were significantly higher inpatients with stage;the expression levels of ADM in distant metastasis were higher than thosewithout metastasis patients, the difference was statistically significant (P<0.05).3. hU II and its receptors were higher expressed in cancer tissues of NSCLC than theadjacent tissues, the expression of IMD in patients with were significantly higher in patientswith stage-; the expression levels of ADM in distant metastasis were higher than thosewithout metastasis patients, the difference was statistically significant (P<0.05), hU II expressedhigher in cancer tissue of adenocarcinoma patients than squamous cell carcinoma patients, thedifference was statistically significant (P<0.05).4. URP was higher expressed in cancer tissues of NSCLC than the adjacent tissues, thedifference was statistically significant (P<0.05). the expression of URP in NSCLC patients, withdifferent pathological types, TNM stages, with or without distant metastasis had no significantcorrelation, the difference was no significant difference (P>0.05).5. Expressions of hU II and UT in cancer tissue and adjacent noncancerous tissues showedsignificant positive correlation (r=0.979, P<0.01; r=0.786, P<0.01). Expressions of URP andUT was no significant correlation In cancer tissue and adjacent noncancerous tissue,there was nosignificant difference (P>0.05). 6. In cancer tissues,the expression levels Of RAMP1, RAMP2and RAMP3were as follows:RAMP3> RAMP2> RAMP1(P <0.05), In the adjacent tissues, the expression levels Of RAMP1,RAMP2, RAMP3were as follows: RAMP2> RAMP3> RAMP1.Conclusions:1. The expression of ADM, IMD and hU II in cancer tissues are higher than in adjacenttissues.and the expression level is contact with the TNM stages and lymph node metastasis, weinfer that the ADM IMD, hUII may be involved in the development of lung cancer.2. HUII express higher in patients diagnosised adenocarcinoma than squamous cellcarcinoma, To detect the expression of might become one of the indicators of the clinicaldiagnosis of lung adenocarcinoma.3. We found for the first time that in this study, the URP express higher in cancer tissues ofNSCLC patients the adjacent tissues, URP may participate in development of NSCLC.4. In cancer tissues and adjacent tissues, expression of hUII and UT showed a significantpositive correlation, it informed us that hUII may play a more important role in the process ofdevelopment of NSCLC compared with URP.5. In the cancer tissues, the RAMP3is the highest expression, in adjacent tissues theRAMP2expression is highest, RAMP3may play a major role in the development of NSCLC.