Expression Of SSTR2A,SSTR5 And EGFR In Non-smallcell Lung Cancer And Their Clinical Signification

BackgroundsLung cancer is one of the five malignant tumors, but it has become the most killing tumor recently with the increase of its incidence and mortality. In the past five years, even related therapies have been improvement a lot, its survival rate is still in low. As to the treatment of non-small cell lung cancer (NSCLC), besides the existing surgery, chemotherapy, actinotheraphy and immunotherapy, molecular targeted therapy for different targets is applied to clinical treatment.Somatostatin receptor (SSTR), as a genic tumor marker, has drawn more and more attention from researchers. With the successful clone of its five subtypes, researchers have been deepening their research on the amino acid sequence, the molecular biological property, the distribution and expression of normal tissue and tumor tissue and specificity ligand of SSTR family. Autoradiography on slices of tumor tissue, observation and analysis on the combination of ligands of tumor homogenate have testified that the high-density expression of SSTR exists in many neuroendocrine tumors. Since 1990s, advanced molecular biotechnologies (e.g. in situ hybridization, RT-PC, Norhern marking) have been used to study the mRNA of SSTR subtypes, and their results indicate that rate of SSTR positive expression in neuroendocrine tumors is over 70%. Recent RII (Radio immuno imaging) studies have found that besides the neuroendocrine tumors, some non-neuroendocrine tumors (e.g. breast carcinoma, non-small cell lung cancer, colon cancer) also have the high-density SSTR which can be observed by scintilla imaging. It is a reliable reference for the location, diagnosis and targeted medical treatment of tumors. As to how SST inhibits tumor proliferation, it is held that the SSTR in tumor cells inhibits the mitosis signal of kinase of growth factor acceptoz straightly, resulting in the stagnation of tumor's growth or the apoptosis of tumor cells; or it is held that the SSTR of high-density expression in tumor-adjacent blood vessel walls inhibits tumor proliferation by inhibiting the formation of blood vessels, stimulating their intense contraction and regulating immunocyte. It is possible that SST, as an important hormone-regulating peptide to inhibit cell proliferation and differentiation, and its analogues (SSA) will become an anti-tumor drug. The high-density expression of EGFR in many malignant tumors (including NSCLC) is closely related to the proliferation of tumor cells, generation of tumor blood vessel, adhesion, attack, metastasis and apoptosis of tumor cells. Since the EGFR tyrosine kinases is a necessary condition in the transmission of signals, it becomes an important targeted molecule in tumor treatment. The present study aims to find out the relationship between SSTR subtypes and clinical pathological factors, the correlation between SSTR2A, SSTR5 and EGFR, the survival period of prognosis through studying the expression of SSTR2A, SSTR5, EGFR in NSCLC and normal tumor-adjacent lung tissues. It will shed light on the targeted therapy of NSCLC. 一, Subjects and methodologies1. Subjects: 69 NSCLC paraffin-embedded specimens, which were removed in radical surgery and verified pathologically from August 1999 to February 2005, of Thoracic Surgery Department of Jinan Military Region General hospital and Qilu Hospital. Among them, 62 NSCLC tissue specimens consist of the investigation group, and the other 7 tumor-adjacent lung tissues (10cm from tumor at least) consist of the contrast group.2. Methodology: All the specimens are fixed by formalin, embedded by paraffin, sliced serially, marked with immunohistochemical markers by rabbit anti-human SSTR2A polyclonal antibody, SSTR5 polyclonal antibody, EGFR monoclone antibody and colored by DAB color appearance system to show out their expression in those specimens. Data of groups are analyzed statistically, together with their clinical pathological data (e.g. size of tumors, age, sex of patients, type of tumor tissue, TNM stages, lymph-node metastasis, etc.) to probe into the relation between expression of the three albumens in 62 NSCLC tissues and 7 normal tumor-adjacent lung tissues and the clinical pathological symptoms of lung tumor, followed by a survey in prognosis.二, ResultsExpression of SSTR2A in those sliced tissues are distributed like yellow-brown grains in cell membrane; expression of SSTR5 are in cytosol and cell membrane; expression of EGFR is mainly in cell membrane and cytosol, distributed diffusively or like grains.1. In the 7 tumor-adjacent lung tissues, no expression of EGFR is found; the positive rates of SSTR2A and SSTR5 expression are 1/7 and 2/7 respectively.2. In the 62 NSCLC tissues, 30 have positive expression of SSTR2A, accounting for 48.3%; 44 have positive expression of SSTR5, accounting for 70.9%; 35 have positive expression of EGFR, accounting for 56.4%.3. The expression of SSTR2A and SSTR5 is closely related to the TNM stages of NSCLC (P<0.05), but insignificantly related to age, sex, smoking of patents, pathological types, size of tumors and lymph-nod metastasis (P>0.05). In the same group, the expression of EGFR is insignificantly related to age, sex, smoking of patients, type of tumor tissue, size of tumors, TNM stages, pathological grades and lymph-nod metastasis (P>0.05). The expression of SSTR2A albumen and SSTR5 albumen has a negative correlation with the expression of EGFR albumen.4. As to the expression of SSTR2A, the three-year survival rate of positive group is 64.52%, higher than the negative group (45.16%) with Log-rank test result as 4.56; their difference is significant statistically (P<0.05); the average survival period of the negative group is 32 months, shorter than that of the positive group (36 months) (P= 0.326, P> 0.05). As to the expression of SSTR5, the three-year survival rate of the positive group is 65. 91%, higher than that of the negative group (22.22%), with Log-rank test result as 4.01 (P<0.05); their difference is significant statistically; the average survival period of the negative group is 32 months, shorter than that of the positive group (40 months) (P=0.453, P>0.05). As to the expression of EGFR, the three-year survival rate of the negative group is 69.44%, higher than that of the positive group (30.77%), with Log-rank test result as 12.41; their difference is significant statistically (P<0.05); the average survival period of the positive group is 24 months, shorter than that of the negative group (50 months) (P= 0.004, P<0.05).四, ConclusionsThe expressions of SSTR2A albumen and SSTR5 albumen are negatively correlated with that of EGFR albumen. The biological behavior that expression of SSTR2A, SSTR5 and EGFR has an affect on NSCLC will shed light on the clinical treatment of NSCLC lymph-node metastasis, pathological staging and prognostic evaluation.Somatostatin receptor (SSTR) as a marker gene in tumors ,is being valued researcher's gradually. With five subtypes have been identified , the people to in the somatostatin receptor family various members' amino acid sequence, the molecular biology characteristic, match aspect the and so on body in the normal tissue and the tumor organization's distribution and the expression and its the specificity research also further deepen.We investigate the expression and significance of SSTR (SSTR2A, SSTR5 ) and EGFR in human non-small cell lung cancer (NSCLC), and to evaluate the relationship of them.