| Background and ObjectiveMany malignant tumors such as gastric cancer's occurrence related to gene mutation,for example,the activation of oncogene and inactivation of tumor suppressor. In recent years,the occurrence of gastric cancer was gradually increase. The surgical treatment was the main treatment method for early gastric cancer and carcinoma in situ, but the rate of recurrence in situ or distant metastasis was high. Various kinds of clinic research has to study the chemotherapy for gastric cancer,for example,5-FU,DDP,paclitaxel has some effect on gastric cancer,but the effective rate of combined with or without chemotherapy yet less than 50%.Aktl(serine-threonine kinase),plays an important role in biological process,such as cell proliferation,metabolize and oncogenesis.Aktl has three subtypes:Aktl (PKBα), Akt2 (PKBβ) and Akt3 (PKBγ), they had different expression levels and function in many tissues. AKT1 suppresses apoptosis,stimulates the prolifertion of the cells,stimulates the growth of the placenea,meanwhile participates in candy metabolization.Akt2 plays an important role in candy metabolization and colon cancer metastasize.Akt3 has fewer report in vitro and in vivo research.Akt was actived and high expressed in many tumors,such as pancreatic cancer,thyroid cancer,colon cancer etc.ERCC1 (excision repair crosscomplementing 1,ERCC1)was necessarily DNA repair gene for cell survival,can detects the damaged DNA and remove it,the expression level can reflect the activity level of NER,meanwhile was the key enzyme of repair for platinum based chemotherapy caused genetic damage,was closely related to drug resistance.In recent years many studies proposed that,high expression level of ERCC1 and Aktl was related to platinum-based resistance and prognosis.To provide the basis for gastric cancer chemotherapy.Aktl related to the growth of tumor cells,proliferation,invasiveness,metastasis and angiogenesis.Because of individual variation,few patients has benefit from adjuvant chemotherapy.Detect the special gene change for sensibility and drug resistance mark, indicated prognosis,can make therapy more individual,effective,and avoid unnecessary side effects. This study used the RT-PCR to detected the expression rules of ERCC1 and AKT1 in cancerous tissues and pericarcinoma tissues,to know the clinical significance. Provide new ways for tumor detect and treatment.Material and MethodGastric cancer tissues and pericarcinoma tissues were obtained from 51cases of gastric cancer patients who underwent surgery in Shandong Provincial Hospital,from march 2008 to March 2009(32 cases of male,19 cases of female),between 34-71 years old. The main method of operation was radical operation, operative patterns were D2 Billroth I,Billroth II or Roux-en-Y gastrojejunostomy. Who can't underwent radical surgery underwent palliative surgery. The tissues were stored in-196℃liquid nitrogen.21cases in stage I,12cases in stageⅡ,14cases in stageⅢ,4 cases in stageⅣ. According to international TNM staging standing (UICC, 1997). To detected the expression of ERCC1 and AKT1 by RT-PCR,β-actin used as internal control, the average expression level was 6.1×103,the expression level>6.1×103 was high level(+),<6.1×103 was low level(-). The postoperation of stage I partly no chemotherapy,stage II-IV underwent chemotherapy, adopted DDP+5-FU+EPI or oxaliplatin+5-FU,21 days per cycle, underwent 4-6 consecutive cycles. Followed to Oct 2009,to observe the difference of ERCC1,AKT1 expression level in with or without lymph node metastasis,differences in different stage and the relationship to prognosis. Results1.Pericarcinoma tissue expressed higher than gastric cancer tissue.2.Gastric cancer tissue without lymph node metastasis expressed higher than with lymph node metastasis.3.ERCC1(+),AKT1(+) in stage I had better prognosis than ERCC1(-),AKT1 (-),both of ERCC1,AKT1 positive had better prognosis.But ERCC1(+),AKT1(+)in stage II-IV had bad prognosis than ERCC1 (-),AKT1 (-).Conclusion1.Pericarcinoma tissue expressed higher than gastric cancer tissue,had significant differences in with or without lymph node metastasis,gastric cancer tissue without lymph node metastasis expressed higher than with lymph node metastasis(p<0.05),this result showed that the lower express of ERCC1,AKT1 related to the occurrence of cancer and metastasis. May be related to ECC1 had function of detected and repaired the damaged DNA.The expression of ERCC1,AKT1 had positive correlation with prognosis.2.Stage II-IV postoperation underwent chemotherapy, priority scheme was platinum-based+5-FU.To observe time over lower expression of ERCC1,AKT1 had longer PFS than higher expression,but in stage I high expression had longer PFS than lower expression, this result showed that, the higher expression had low sensitivity to platinum-based+5-FU chemotherapy,may be related to the function to repair chemotherapy damaged DNA.3.ERCC1 and AKT1 had different mechanism in different stages,close related to resisitant and prognosis. To detect it in molecular level can further understood malignant degree of gastric cancer,instructed set individualized treatment,and could be a prognostic indicator for gastric cancer. |
