| BackgroundThe incidence of breast cancer, a common malignancy in women, has gradually risen in recent years, which increasingly becomes a threat to the majority of women. Breast cancer is a systemic disease because of the fact that cancer cells can early diffuse by micro-invasion. Although drugs and clinical treatment programs renew constantly, it is difficult to control the morbidity and the prognosis of this cancer, which is one of the most malignant diseases to threaten women’s health. According to clinical data, it has gradually become the most popular type of tumor resulting in death of women. Early diagnosis is a key to improving the cure rate and survival of breast cancer, while the growth and progression of breast cancer cells involve in complex biological processes. Pathological diagnosis is one of the important methods used in the clinical diagnosis of breast cancer, but there is a trouble that it only can be used once by testing for a single indicator, which cannot achieve a good diagnostic result. And it is inaccurate and nonspecific to classify the breast cancer molecularly or to guide the medication, therefore, the clinical needs a specific method to diagnose the breast cancer, which is extremely important for individual treatment.Nowadays pathologic type, clinical stage, estrogen receptor, progesterone receptor, HER-2and so on are used clinically to estimate the prognosis of breast cancer. With the continuous improvement and development of the biological basic and clinical research, breast cancer treatment has also constantly renewed, and new drugs as well as new therapy are emerging, making the breast effects of cancer treatment also have greatly improvement and changes. But there are still some patients with poor prognosis, compared to the good prognosis patients who show off the same clinical stage and pathological type, of course receiving the same drugs and treatment methods. At the same time, whether there is a need to receive chemotherapy for early breast cancer is still inconclusive, and also it is a lack of appropriate criteria.Although, compared with other solid tumors, treatment of breast cancer in the clinical has achieved certain success, which improves part of the patients’ quality of life,it does not mean that any kinds of good treatment program are suitable for all patients. More often, the treatment effects are not the same in the same pathology type and the same clinical treatments. So to find an appropriate treatment program for patients to receive the best therapeutic effect has become a long-term goal for today’s clinicians. The main reason leading to the death of patients is metastasis and proliferation of tumor cells, although patients with the same histological type and clinical stage also have various conditions of prognosis. So it is difficult to diagnose and estimate the prognosis from different patients based on today’s clinical classifications and pathological features. Nowadays we can obtain a series changes of metastatic gene which can be highly expressed and diffuse, therefore, the concept of early-stage breast cancer diagnosis by traditional pathology or medical imaging has been changed. In some cases of the patients with early-stage breast cancer, the tumor can grow back or move after radical surgery and normative chemotherapy, so accurate prediction about prognosis for early-stage breast cancer can provide an important basis for individualized treatment and prevention of recurrence. As we all know, breast cancer is a diverse disease with different immunohistochemistry, different molecular characteristics, different pathological type and different genes, which leads to different conditions of prognosis. Also patients with the same histological type and clinical stage can come out to be various conditions of prognosis. Tumor, known as a polygenic disease, grows up and develops at the level of gene, which results in the fact that the patients with same pathologic type and the same clinical stage response differently to the same clinical therapy. Overseas research shows that a typia and diversity of gene should be responsible for the different conditions of prognosis despite of the same histological type and clinical stage, and analysis of genome should be the standard of prognosis, which is more accurate to guide the treatment compared to the clinical pathologic indicators.It is no argument to say that immune expression, biological behavior, morphology and pathology are shown differently under the effect of treatment, and researchers believe this difference due to the differences in the molecule of breast cancer. Continuous research shows that duration of survival or prognosis is closely associated with many molecular markers, thus the study of genotyping has become the basis of molecular biology. At the same time, because of the appearance of high-throughput techniques (Gene chips, tissue microarray, etc.), genotyping can not only reflect the differences of clinical manifestations and prognosis but also provide a support to the study of genotyping on breast cancer theoretically and technically. Differentially expressed genes in tumors of breast cancer is important for genotyping which can truly solve these intractable problems—how to distinguish tumors, how to make neoplasm staging reasonable, how to predict the prognosis and how to make treatment plans. Occurrence of tumor is resulted from multiple genes combination, sequential mutation including oncogene and suppressor gene.Thanks for the constant exploration of study of human genome project, since 2003the researchers have been able to detect the human genome sequence. Today, people have entered an era of post-genome. To explore the configuration and the expression regulation of human’s genome sequence has become an important task of today’s study, and the detection and discovery of gene expression has become a key point of the study on gene function. Biochip technology is the use of microfilm, based on characteristics of the interaction between the different molecules specifically, the discontinuity in the life sciences, expression of integrated silicon chip or glass surface of the micro-biochemical analysis system, in order to achieve protein, fast-accurate detection of a large amount of information cells, genes and other biological components. Depending on the molecular components on the chip, and then the biochip can be divided into protein chip, microarray, cell and tissue microarray chip. Biochip detection equipment and technical methods compared to the past, there are advantages of miniaturization, high throughput, low cost, automated, pollution and other aspects. According to the synthesis of biochip technology, biochip can be divided into chip in situ synthesis and micro matrix. Due to the constant leap of the biochip technology research, the American association for the advancement of science biochip rated one of the top ten sciences and technology breakthrough in1998, it is agreed that biochip technology will be the human beings and a profound technological revolution. Today, the most valuable application of biochip is a gene sequence as the research object of the microarray, also called Gene chips or DNA chip. According to the differences of DNA on the carrier, the chip can be classified as oligonucleotides and cDNA microarray. And based on the different purposes of the gene chip, it can also be classified as fingerprint chip, expression profile chip, toxicology diagnose chip, sequencing chip and so on.30years ago, Bains, etc. have already used the method of biologicalhybrid for the purpose to detect sequence of short DNA on the solid support. Due to Introduction of confoeal laser scanning microscopy, photographic lithography technology, probe microscopy solid-phase technology in situ synthesis, two-color fluorescent probe hybridization, it makes the gene chip technology more commercialized from laboratory. At the same time, the improvement and progress of gene chip technology benefit from the development of molecular biology and other relative subjects as well as Human Genome Project. In1992, the team led by Fodor from Affymatrix first lyreported the in-situ synthesis DNA chip by using semiconductor photolithography technology, which the first piece of gene chip in the world. In1995, the first gene microarray using glass as carrier was invented by P.Brown laboratory from Stanford University, which marked the gene chip began to be widely researched and used.Because of the constant development of the gene chip technology, molecular defects in breast cancer is being found and revealed as the exploration of breast cancer has been developed from the original cellular level into the molecular biology. Accordingly,molecular diagnosis should be more and more important in early diagnosis. By using the gene chip to detect the genotyping of different breast cancer tumor tissues, we can distinguish the differences amount patients with breast cancer, then screen out the gene combination of significance, which provides new reference and basis for individualized treatment of breast cancer.Therefore, to analyze differences from gene expression of different early-stage breast cancer by using the gene chip technology can help us to find the genotyping, which is used to predict the prognosis from patients with early-stage breast cancer. And also we can find out the method of diagnosis, treatment and prevention without delay, which reduces the mortality of patients with early-stage breast cancer and prolongs their survival time. This is the topic of47early-stage breast cancer patients with the same clinical staging followed up by5years. And according to the results of the prognosis with Agilent4x44k human genome-wide Oligo chip used to screen out differentially expressed genes in patient of different prognosis, the selected part can be used to estimate the prognosis of early-stage breast cancer gene. Based on the different genes of prognosis, it provide an important guidance for clinical individualized diagnosis, treatment and the theoretical basis, which can predict the individual prognosis of breast cancer patients differently, thus to choose the appropriate radiation and chemotherapy as well as biological treatment and to improve the survival rate of breast cancer patients of early-stage. ObjectiveAnalysis of the same pathological type, clinical stage (I-II) but the expression of breast cancer prognosis of different genetic differences, screened the gene combination meaningful, look for related with the prognosis of breast cancer gene. MethodsThe Agilent4x44k human whole genome Oligo chip were used to screen47patients with early breast cancer tissue samples, combined with their difference of prognosis, divided into control group and experimental group for differential gene expression analysis. ResultsMicroarray analysis revealed that the experimental group (poor prognosis) sample than in the control group (good prognosis) samples are differentially expressed genes126, of which60genes significantly up-regulated and66genes were significantly down-regulated (differences were more than2times). ConclusionDifferent samples of early breast cancer prognosis, there are significant differences of gene expression, the prognosis of early breast cancer is associated with the expression of these genes. |
PDF Full Text Request