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Manifestation And Interrelationship Of EGFR Genetic Mutation, ERCC1and RRM1Protein In Ⅰ-ⅢLung Adenocarcinoma

Posted on:2013-07-21Degree:MasterType:Thesis
Country:ChinaCandidate:C S YaoFull Text:PDF
GTID:2254330398977025Subject:Oncology
Abstract/Summary:PDF Full Text Request
Background and purposeCurrently, lung cancer has become one of the malignant tumors with high incidences of disease and death on a global scale. Its mortality rate tops various strains of malignant tumors in urban areas in China, thus posing grave threat to people’s health and life. Among the different strains of lung cancer, non-small cell lung cancer accounts for75%-80%of the total. Although early non-small cell lung cancer can be completely removed through medical surgery, it cannot be totally cured; and in most cases, the patient ultimately dies either of relapse or metastasis. Adjuvant therapy after operation improves the survival rate in some of the cases, however, a considerable number of patients suffer from poor treatment. Therefore, it has become the focal issue of research to formulate individualized treatment scheme, pick out patients with certain characteristic symptoms for special treatment, and enhance efficacy of treatment while screening patients from the toxic side effects of adjuvant therapy of postoperation. Currently, EGFR, ERCC1, RRM1, K-RAS etc constitute the most ample evidence as predictive index of NSCLC patients.Relevant researches confirm that NSCLC patients with EGFR genetic mutation are generally characterized by a high rate of response after oral dosage of EGFR-TKIs. Some domestic and overseas researches reveal that in comparison with genetically wild EGFR patients, NSCLC patients with EGFR genetic mutation ought to be subject to platinum-based chemotherapy with high rate of efficacy. However, there also exists an opposite conclusion. Adenocarcinoma accounts for40%-50%of all strains of non-small cell lung cancer, and it is characterized by a year-on-year ascending tendency. In addition, its EGFR genetic mutation is more frequently observed. The current experiment, starting from the relationship between EGFR genetic mutation and DNA repair capability, conducts a retrospective analysis of the manifestation of EGFR genetic mutation, ERCC1and RRM1protein in101cases of Ⅰ-Ⅲ adenocarcinoma after medical surgery, their relationship with clinical pathological characteristics, and the interrelationship between these biomarkers. This is done in an attempt to locate the molecular mechanism possibly existing in this phenomenon, so as to provide theoretical basis for establishing the individualized treatment mode for adenocarcinoma patients after medical surgery, and to provide theoretical support for carrying out molecule-based clinical research of prospective adjuvant therapy of adenocarcinoma of postoperation.MethodsWe collected101I-III adenocarcinoma patients who have undergone operations at Henan Oncology Hospital from March of2010to September of2011. All these patients are subject to postoperative pathological confirmation, and their clinical and pathological characteristics are observed and analyzed. Postoperative pathological specimens of all these cases are collected, and genome DNA is extracted from the paraffin tissue. We detect the mutation of exonsl9and21of EGFR gene with the application of PCR apparatus for fluorescent quantization, and simultaneously detect the manifestation levels of ERCC1and RRM1protein through immunohistochemistry. Furthermore, we carry out an analysis with respect to the manifestation of the molecular indexes of the aforementioned researches, their relationship with clinical pathology and their interrelationship by employing SPSS17.0software package.ResultsA total of99suitable cases are selected for analysis, among which there are46cases with EGFR genetic mutation, accounting for46.5%of all adenocarcinoma patients. EGFR genetic mutation manifests a high likelihood among females and non-smokers, with P value as0.048&0.042respectively. The difference is statistically significant. With reference to such clinical traits as age, size of tumor, lymphatic metastasis and pathological stage, the difference between rates of EGFR genetic mutation is statistically insignificant. Among the99cases of adenocarcinoma,50cases are characterized by a high manifestation of ERCC1protein, accounting for50.5%;49cases are marked by a low manifestation, accounting for49.5%. With reference to such clinical traits as gender, age, smoking habit, size of tumor, lymphatic metastasis and pathological stage, the difference between rates of ERCC1high manifestation is statistically insignificant.52cases are marked by a high manifestation of RRM1protein, accounting for52.5%, whereas47cases are characterized by a low manifestation, accounting for47.5%. With reference to such clinical traits as gender, age, smoking habit, size of tumor, lymphatic metastasis and pathological stage, the difference between rates of RRM1high manifestation is statistically insignificant. EGFR genetic mutation is negatively correlated with ERCC1protein manifestation (P=0.035) and uncorrelated with RRM1protein manifestation; and there likewise exists no correlation between ERCC1and RRM1protein manifestations.Conclusion1. Among adenocarcinoma patients, EGFR genetic mutation rate stands at46.5%, and is marked by a high rate among females and non-smokers. With reference to such clinical traits as age, size of tumor, lymphatic metastasis and pathological stage, the difference between rates of EGFR genetic mutation is statistically insignificant.2. Among adenocarcinoma patients, high and low manifestation of ERCC1protein stands at50.5%and49.5%respectively. With reference to such clinical traits as gender, age, smoking habit, size of tumor, lymphatic metastasis and pathological stage, the difference between rates of ERCC1high manifestation is statistically insignificant.3. Among adenocarcinoma patients, high and low manifestation of RRM1protein stands at52.5%and47.5%respectively. With reference to such clinical traits as gender, age, smoking habit, size of tumor, lymphatic metastasis and pathological stage, the difference between rates of RRM1high manifestation is statistically insignificant.4. Among adenocarcinoma patients, EGFR gene mutations in lung adenocarcinoma patients with low ERCC1protein expression is more common, and the difference was statistically significant (P=0.035). EGFR genetic mutation is uncorrelated with RRM1protein manifestation, and there likewise exists no correlation between ERCC1and RRM1protein manifestations.5. Adenocarcinoma patients with EGFR genetic mutation are marked by a low manifestation of ERCC1protein. Hence, platinum-based chemotherapy can be taken as the standard therapy for adenocarcinoma patients with EGFR genetic mutation. Further researches ought to be conducted in this regard.lung...
Keywords/Search Tags:lung adenocarcinoma, EGFR genetic mutation, ERCC1proteinmanifestation, RRM1protein manifestation, correlation
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