| Background According to the 2015 China Cancer Statistics Report,the latest data shows that the incidence and mortality of gastric cancer in China ranked second [1].The incidence of gastric cancer is increasing year by year worldwidely and about 60% of the annual number of new gastric cancer cases occur in china.The incidence of gastric cancer in China,Japan and South Korea accounted for about 70% of the total number of gastric cancer in the world.The mortality rate of gastric cancer ranked second in various tumors in the world.The cause of gastric cancer has not been clear,but the high risk factors closely related to the occurrence and development of gastric cancer includes diet,environment,infection,genetic susceptibility and gene,all of which have been confirmed by many studies [2-6].Surgical resection of gastric cancer in early onset is often regarded as the best treatment.However,as the early screening of the disease failed to timely found it and people have weak cognition,the early gastric cancer is detected at a very low rate.The so-called progress stage of advanced gastric cancer,which is the mid or late gastric cancer,accounts for most of the overall treatment of gastric cancer.Most of them have missed the best time for surgery and they need kinds of comprehensive treatments including chemotherapy,radiotherapy,heat treatment,immunization therapy as well as traditional Chinese medicine treatment.Although systemic chemotherapy is the main treatment measure,a large number of Meta analysis showed that it could prolong the survival time.However,the results can still not achieve the ideal expectation.The relevant data shows that the five-year survival rate is about 20% after radical resection of advanced gastric cancer is done in China.The 2016 edition of the guidelines for the detection of gastric cancer HER2 noted that both To GA and Her MES have demonstrated the efficacy of trastuzumab,an anti HER2 target drug,in the treatment of HER2 positive advanced gastric cancer.In 2015,the NCCN guidelines listed docetaxel,cisplatin,and fluorouracil(DCF)regimens as first-line regimens for advanced gastric cancer.It is undoubted that the realization of the human genome project brings more hope to patients with gastric cancer under the background of "precision medicine”.Molecular targeted therapy system is becoming more and more mature,which is essentially due to the molecular biology and genomics that come from laboratory to clinic,making a big forward and completely changing the previous single,rough treatment mode.Gradually it comes to an era with the individualized treatment on the basis of molecular targeted therapy.Through the detection of different individual markers and combination of molecular targeted drugs selected according to different individuals and chemotherapeutic drugs,patients' disease progression time and overall survival time can be better extended.It has been widely recognized that the II epidermal growth factor receptor HER2,one of the human EGFR receptor super family member,acts as an important marker in targeted therapy and prognostic prediction of breast cancer.In addition,this receptors are found in other parts with malignant tumors except mammary cancer,mainly including ovarian cancer,colorectal cancer and lung cancer.Type II epidermal growth factor receptor HER2 also exists in gastric carcinoma.HER2 gene amplification can be used as an effective target for targeted therapy of gastric cancer.There is a close relationship between the over expression of HER2 protein and the prognosis of gastric cancer.The resistance problems of chemical drugs in the treatment of gastric cancer is also an important factor affecting the prognosis of gastric cancer.Platinum anticancer drugs and ERCC1 gene,fluorouracil anticancer drugs and TYMS gene,taxanes antitumor drugs and TUBB3 gene,those three kinds of chemotherapeutic drugs corresponds respectively to three genes,which also have a close relationship and play a very important role in individualized chemotherapy in patients with gastric cancer.By using real time fluorescence quantitative PCR,the q RT-PCR technique,the ERCC1,TUBB3,TYMS gene m RNA expression level are detected.The corresponding group of chemical drugs,DDP(C),Docetaxel(D)and 5-FU(F)are selected to form the chemotherapy regimen DCFf which is commonly used in clinical.The combination of multiple genes in selecting the chemotherapy drugs in the treatment of patients with gastric cancer can be more targeted and improve the therapeutic effect.Targeted drugs and chemotherapeutic drugs in the treatment of gastric cancer alone have an amazing effect.However,whether the combined treatment of targeted drugs and chemotherapeutic drugs in the treatment and prognosis of diseases is better than pure treatment of these two,this paper made a further research about it.Immunohistochemical staining method(immunohistochemistry,IHC)is used to detect the expression of HER2 protein in gastric cancer tissue,and fluorescence in situ hybridization(fluoresce in situ hybridization,FISH)is used to detect the state of HER2 gene in gastric carcinoma.The real-time quantitative PCR detection(realtime quantitative PCR,q RT-PCR)is used to detect the MRNA expression level of Commonly used chemotherapeutic drugs fluorouracil,platinum and taxane in gastric cancer,investigate the Criteria for gastric cancer using FISH,IHC,q RT-PCR technology,in order to better provide a quantitative reference for the benefit of anticancer drugs in the treatment process and to guide the rational use of drugs in individualized treatment.Objective The objective is to investigate the significance of HER2 gene amplification in gastric cancer tissues and the combined detection of three kinds of chemotherapeutic sensitive markers.Methods 120 cases of radical gastrectomy for gastric and gastroesophageal junction by surgical resection are collected from February 2011 to September 2013 in the 150 th Central Hospital of PLA,Luoyang.The expression of HER2 protein,HER2 gene amplification and expression of ERCC1,TUBB3 and TYMS gene in 120 cases of gastric cancer were detected by SP immunohistochemical staining,fluorescence in situ hybridization and real-time quantitative PCR detection(m RNA).Results 1.The expression of HER2 protein in 120 cases of gastric carcinoma: the positive expression rate of HER2 protein is 40.8%(49/120),among which HER2 protein 3+ is 10.8%(13/120);HER2 protein 2+ is 14.2%(17/120);HER2 protein 1+ is 15.8%(19/120).2.The amplification rate of HER2 gene in 49 cases of HER2 protein expression is 38.8%(19/49).According to the result of the SPSS output,the Kappa value here is 0.870,which shows the consistency of the two results is higher.The obtained Kappa values were tested,according to the Kappa value of the test value of P(approximate SIG),test P value is 0,that the calculated Kappa was not zero,and has statistical significance,according to the Kappa value judgment,and ultimately determine the expression levels of IHC and FISH is same,and high consistency.3.Detection results of ERCC1,TUBB3,TYMS m RNA gene expression in 120 cases of gastric carcinoma: low expression in 41 cases among single genes,low expression in 45 cases among double genes;ERCC1,TUBB3,TYMS gene have low expression in 19 cases,no middle and low expression in 15 cases.4.Chooaw HER2 gene amplification,combined with chemotherapy drug sensitivity markers ERCC1,TUBB3,TYMS gene m RNA expression leve,and according to the difference of three genes in patients with low expression in different ways,combined treatment of chemotherapy and divided into two groups,the combined program PFS and OS values were significantly different from DCFf scheme.And according to the difference t test P value,the difference of two indexes is significant.What's more,according to the average of two schemes of PDF and OS,combination is higher than DCFf,further illustrates that the combined scheme is better than DCFf scheme.Conclusions 1.The expression of HER2 protein and HER2 gene status in gastric cancer tissues have high similarity.2.Different expression patterns of HER2 have potential guiding significance for targeted therapy of gastric cancer.3.In patients with positive HER2 expression,trastuzumab is superior to chemotherapy alone. |
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