Font Size: a A A

The Expressions And Clinical Significance Of LRIG1 And EGFR In Human Gastric Carcinoma

Posted on:2010-04-10Degree:MasterType:Thesis
Country:ChinaCandidate:X S YangFull Text:PDF
GTID:2144360275469492Subject:Surgery
Abstract/Summary:PDF Full Text Request
Objective: Gastric carcinoma is one of the most common malignant tumors in the world. The morbidity in China is 25.2 per 100 000, which makes it to be the first leading cause of cancer death. The development and progression of gastric carcinoma are complex processes which involve in the activation of oncogenes and inactivation of anti-oncogenes, resulting in the changing of biological behavior of cells in vivo. Clinical studies show that more than 60% patients who have suffered from advanced gastric carcinoma will lose their lives because of recurrence and metastasis of tumor, even though the positive treatments including operation and/or chemotherapy have been put into practice. Thus, it appears vital clinical significant to research the molecule mechanisms and find out the new therapeutic methods of gastric carcinoma.Different factors and different genes play a different role in the development and progression of tumor. The cell microenvironment and cell interaction with extra cellular matrix (ECM) play an essential role in many physiological and pathological processes. The ECM can actively regulate cellular proliferation, migration, and adhesion, which influence embryonic development, tissue morphogenesis and angiogenesis as well as tumor transformation and metastasis. And in molecular mechanism, tumor development is characterized by a severe aberration in the interaction of tumor cells between the activation of oncogenes and inactivation of anti-oncogenes.Tandem leucine-rich repeats and immunoglobulin-like domains-1(LRIG1) is a transmembrane carbohydrate protein, which is induced from epidermal growth factor(EGF), and the combination of LRIG1 and epidermal growth factor receptor(EGFR)can lead to negative feedback effects. LRIG1 gene is situated in the 3p14.3 position of human chromosome.The sequence is 4763bp long, which coding 1093 amino acids.Tumor gene in the 3p14.3 position of human chromosome can be tested heterogeneous deletion among lots of human tumors. Thus, LRIG1 gene may be a tumor suppressor gene. The expression of LRIG1 protein was tested in much human tissue and parts of human tumors by Nilsson etc, study show that the expression level of LRIG1 gene in tumor tissue was lower or deletion than in normal tissue, which show that the LRIG1 gene may have a relationship with the development and progression of tumor.Epidermal growth factor receptor ( EGFR ) is a transmembrane receptive carbohydrate protein, EGFR gene is situated in the 7p13-q22 position of human chromosome.The sequence is 110kb long, which coding 170KD carbohydrate protein, which generally express in human epidermal cell and matrix cell. We can test that the abnormal RNA record or higher expression of EGFR in lots of human tumors, all of that points out that the EGFR may play a part in the development and progression of tumor. Study show that EGFR control the growth of tumor through signal transmission. In addition, it's closely associated with angiogenesis, tumor invasion and metastasis. The proliferation, angiogenesis, adhesion, invasion, metastasis and repress apoptosis of tumor cell can be promoted by the higher expression of EGFR. At present, it's not very clear that the record control, protein process following translation and transportation mechanism of EGFR. It is one of the researching focuses that the signal network about EGFR.To investigate the mRNA expression level of LRIG1 and EGFR in human gastric cancer tissues, matched para-cancer tissues and normal tissues, and to determine the relationship between expression of the two markers and the development or progression, and biological behavior, respectively, which may provide the theoretical foundation for prognosticating of invasion and metastasis of gastric cancer, and guiding the reasonable comprehensive treatment.Methods: put gastric cancer tissues, matched para-cancer tissues and normal tissues obtained from 40 patients with gastric cancer in the -80℃freezer, divide it into groups on the basis of the standard of diagnosis and treatment of gastric cancer. The mRNA expression level of LRIG1 and EGFR is investigated by reverse transcription polymerase chain reaction (RT-PCR) in human gastric cancer tissues, matched para-cancer tissues and normal tissues. ?-actin is designed as reference standard. We used SAS V8 software package to analyze the data, the difference was considered as significance if P<0.05.Results:1 The expression level of LRIG1 mRNA in gastric cancer tissues(0.51±0.13)is lower than that in matched para-cancer tissues(0.85±0.17) and normal tissues(1.26±0.16)(P<0.05);.2 The expression level of EGFR mRNA in gastric cancer tissues(4.42±0.85)is higher than that in matched para-cancer tissues(2.64±0.80) and normal tissues(1.73±0.87)(P<0.05);3 The expression level of LRIG1 mRNA is not correlated with sex, years, location, histological grade, the depth of invasion, metastasis of lymph node, and the staging (P>0.05);4 The expression level of EGFR mRNA is not correlated with sex, years, location, histological grade, the depth of invasion, metastasis of lymph node, and the staging (P>0.05);5 There is negative correlation between the expression level of LRIG1 mRNA and EGFR mRNA in human gastric cancer tissues, matched para-cancer tissues and normal tissues ,there were significant differences between them(r=-0.686; P <0.05).Conclusions:1 The expression level of LRIG1 mRNA is lower in gastric cancer tissues than that in matched para-cancer tissues and normal tissues, which may reveals that the lower expression of LRIG1 mRNA leads to the reduction of inhibition signal to EGFR and active it, that cut down the regulations of negative feedback to EGFR, results in tissues cells reproduced and survival, it may involves the progression of gastric cancer and LRIG1 gene may be an anti-oncogene.2 The expression level of EGFR mRNA is higher in gastric cancer tissues than that in matched para-cancer tissues and normal tissues, which demonstrates that the reduction of inhibition signal to EGFR leads to the high expression of EGFR, it obstrucs the signal system of growth factor, thus, the growth of cell lose control and deteriorate, become a tumor cell, and repress apoptosis of tumor cells.3 The expression level of LRIG1 mRNA is not correlated with sex, years, location, histological grade, the depth of invasion, metastasis of lymph node, and the staging, which is show the expression level of LRIG1 mRNA can't determine the pathological staging.4 The expression level of EGFR mRNA is not correlated with sex, years, location, histological grade, the depth of invasion, metastasis of lymph node, and the staging, which is different from other documents. It may because of the small sample or the difference of sample classification.5 There is negative correlation between the expression level of LRIG1 mRNA and EGFR mRNA in human gastric cancer tissues, matched para-cancer tissues and normal tissues, there were significant differences between them, which suggests that LRIG1 may be a direct or indirect regulator to EGFR, which negatively feedback to EGFR, EGF positively feedback to LRIG1, but LRIG1 negatively feedback to EGFR, keep relatively balance, and make tissue metabolism stable.
Keywords/Search Tags:gastric carcinoma, development and progression, invasion and metastasis, LRIG1, EGFR, RT-PCR
PDF Full Text Request
Related items