The Expression Of ERCC1, P27^kip1, CyclinE And Its Relationship With Prognosis In Gastric Cancer

Background and ObjectivesGastric cancer is the most common digestive malignant tumor in the world and the second most frequent cause of cancer death, affecting about 13.8 cases per 100,000 persons every year. Satisfactory effect can not be got only by surgery because gastric cancer is a general disease. Therefore synthetic therapy of surgery combined with chemotherapy and radiotherapy should be employed to enhance the survival rate. Traditional chemotherapy medicine has five kinds, including anti-metabolism, alkylating agent, antibiotics, platinum and plants. With the development of modern molecular biology and cellular biology, targeted medicine came into being which can treat cancer. Targeted medicine plays an important part in anti-neoplasms by target point and has advantageous group itself. Recently, researches have found chemotherapy medicine also had advantageous group, just as targeted medicine. Now main question we are faced with is "how to screen the advantage group, so that the greatest benefit in patients receiving chemotherapy, to avoid over-treatment". The excision repair cross complementing group1 (ERCC1) gene carry out damage repair of the DNA via the nucleotide excision and repair pathway, which is essential for the repair of the cisplatin-DNA adducts. If DNA damage can not be repaired in time, it would lead to cell proliferation and cause cancer. Meantime, this gene in tumor cells to cisplatin resistance mechanisms plays a important role. It has been reported that the overexpression of the ERCC1 gene had a poor prognosis in lung cancer patients who received cisplatin-based adjuvant therapy after surgery. The cell cycle plays an important role in the development of cancer. Most of the molecular alterations are related to the gene in cell cycle regulation, including cyclin-dependent kinases(CDKs), cyclin-dependent kinase inhibitors (CDKIs) and Cyclin(A, D, E), which are the major regulatory factor of cell cycle. Cyclin-dependent kinases2 (CDK2) is one of the most important regulatory factor in G1/S of cell cycle, which play a positive role in G1/S when combines CyclinE, but it plays a negative role in G1/S when combines P27Kip1 (kinase inhibition protein27). Therefore, P27Kip1 and CyclinE form an adverse relationship in G1/S, which complete regulation of cell cycle and normal cell proliferation. Some scholars have found that downexpression of P27Kip1 and overexpression of CyclinE might be associated with the progress and prognosis of esophageal cancer. But the expression of ERCC1, P27Kip1 and CyclinE is unclear in gastric cancer, and the results of their impact on prognosis of gastric cancer are also inconsistent. Therefore, this study selected the ERCC1, P27Kip1 and CyclinE three indicators to explore them with the development of gastric cancer and its relationship with patient survival, clinical efficacy and prognosis prediction to provide a theoretical basis.Materials and Methods1 To collect 45 cases of gastric cancer and 10 cases of normal gastric tissue with clinicopthologic data and follow-up.2 To detect expression of ERCC1, P27Kip1 and CyclinE expression in gastric cancer and normal gastric tissue by immunohistrochemistry assay (ElivisionTM).3 To accepte chemotherapy of platinum and fluorouracil in 45 cases gastric cancer, specific schema, cisplatin,25mg/m2, d1-3. Leucovorin,0.1, d1-5. Fluorouracil, 50mg/m2, d1-5, transfusion, which should be experimented every three weeks, the media period 5. After the operation every 2-3 months line chest or ventrum spiral computed tomography examination time to tumor recurrence or metastasis. All patients had recurrence and metastasis by imaging, endoscopy and biopsy. None received preoperative radiotherapy or chemotherapy, all specimens by routine formalin-fixed, paraffin-embedded.4 To analyze ERCC1, P27Kip1 and CyclinE expression with various clinicopathological parameters and survival relationship in SPSS 11.0.Results1 The positive rate of ERCC1, P27Kip1 and CyclinE in gastric cancer was 31.1% (14/45),35.6%(16/45) and 55.6%(25/45). The positive rate of ERCC1, P27Kip1 and CyclinE in normal gastric tissue was 70%(7/10),80%(8/10) and 20%(2/10). There were the significant differences between two groups (P<0.05).2 The expression of ERCC1, P27Kip1 and CyclinE in gastric cancer was not correlated with sex, age, size, site of tumor and degree of differentiation (P>0.05). The expression of ERCC1, P27Kip1 and CyclinE in gastric cancer was related to depth of invasion, lymph node, distant metastasis, clinical stage (P<0.05).3 There was significantly negative correlationship between P27Kip1 and CyclinE expression in gastric cancer. The coefficient correlation was-0.47 (P<0.05).4 The median disease-free survival of patients with ERCC1 and P27Kip1 positive in gastric cancer was 6.8 and 12 months, respectively. There was significant differences between positive and negative expression of ERCCl, P27Kip1 (P<0.05). Median disease-free survival of patients with CyclinE positive and negative in gastric cancer was 13 and 15 months, respectively. There was not significant differences between CyclinE positive and negative (P>0.05).5 The positive of both ERCC1 and P27Kip1 was 7 cases (15%), negative of both ERCC1 and P27Kip1 was 22 cases (48%). ERCC1 positive and P27Kip1 negative were 7 cases (15%), ERCC1 negative and P27Kip1 positive were 9 cases (20%). Median disease-free survival of the four groups was 6.8,28.1,11.2 and 24.6 months, respectively. There was significant difference between median disease-free survival of patients with both ERCCl and P27Kipl positive or both ERCC1 and P27Kip1 negative or ERCC1 positive P27Kip1 negative (P<0.05). There was no significant difference between ERCC1 negative and P27Kip1 positive (P>0.05). Conclusions1 The low expression of ERCC1, P27Kip1 and the high expression of CyclinE were related with the occurrence and development of gastric cancer.2 The expression of ERCC1, P27Kip1 and CyclinE in gastric cancer was not correlated with sex, age, size, site of tumor and degree of differentiation. The expression of ERCC1, P27Kip1 and CyclinE in gastric cancer was related to depth of invasion, lymph node, distant metastasis, clinical stage.3 There was significantly negative correlationship between P27Kip1 and CyclinE expression in the development of gastric cancer.4 The gastric cancer patients receiving platinum-based and fluorouracil chemotherapy, median disease-free survival of patients with ERCC1, P27Kip1 and CyclinE positive was shorter than those with negative expression. They showed that patients with ERCC1, P27Kip1 and CyclinE positive were associated with short survival and poor prognosis.5 To detect ERCC1, P27Kip1 and CyclinE may predict effect of chemotherapy and evaluate prognosis.