Relationship Between Expression Of Livin In Gastric Cancer Tissues And Tumor Chemotherapeutic Sensitivity

Objective: The gastric cancer is the most common malignant tumors in the digestive system. At present, the mortality of the gastric cancer is the second in all of tumors worldwide and the first place of malignant tumors in our country. Most of patients with this disease are diagnosed in advanced stages, and lost the chance of surgical treatment. Despite recent progress in chemotherapy, the overall survival rate advanced stages is still low. Apoptosis resistance of gastric cancer cell of gastric cancer patients in may be one of many reasons, and has increasingly become one of the hot spot of research fields. Inhibitor of apoptosis protein family may play a key role in cause apoptosis resisitance, and have become the focus of research increasingly. Livin is a novel inhibitor of apoptosis protein (IAP) family member, and it has two isoforms, Livinαand Livinβ. The relationship between its up-regulation and gastric cancer occurrence progress and tumor chemotherapeutic sensitivity remains uncertain. The aim of this study was to study the expression of Livin protein and Livin mRNA in gastric cancer tissue and normal gastric mucosa and corelations with clinical pathology character and its relationship with tumor chemotherapeutic sensitivity. Livin may act a new target for apoptosis-inducing therapy of gastric cancer. Their detection can help us to select anticancer drugs, thus to implement Individualized chemotherapy.Methods: In this study, we select 50 samples of gastric cancer and samples of normal gastric mucosa (>5.0cm). These patients had gastrectomy in the 4th hospital of HeBei Medical University from October 2005 to March 2006. The samples were proved adenocarcinoma by pathology and detected the expressions of Livin protein by S-P immunohistochemical technique. We select 40 samples of gastric cancer and samples of normal gastric mucosa (>5.0cm). These patients had gastrectomy in the 4th hospital of HeBei Medical University from September 2006 to June 2007. The samples were proved adenocarcinoma by pathology and detected the expressions of Livin mRNA by reverse transcription polymerase chain reaction (RT-PCR).All samples are without chemotherapy or radiotherapy before surgery. The relationship between the expressions of Livin and the biological behavior of gastric carcinoma were analyzed, including patients'sex, age, tumor location, size, infiltration depth, differentiate extent, clinical stages and lymph node metastasis.In addition, we select one chaw tumor tissue from all the samples of gastric carcinoma. These tumor tissues were treated by mechanical dispersion method for single cell suspension respectively. The OD values were detected by MTT method and the CI values to 9 kinds of chemotherapy scheme, CTX,VCR,ADR,CDDP,5-Fu,MMC,L-OHP,CPT-11,VP-16, were calculated according to the formula.And analyze relationship between the expressions of Livin and tumor chemotherapeutic sensitivity.Results:1 The results of Livin protein expression in gastric cancer tissues detected by S-P immunohistochemical technique1.1 Exprssion of Livin protein in gastric cancer tissues The positive rates of Livin protein were 62.00% in gastric cancer tissues, but only 12.00% in normal gastric mucosa. The expressions of Livin in gastric carcinoma tissues were significantly higher (P<0.05).1.2 Correlations between the expression of Livin protein in gastric cancer tissues and clinical biological characteristicsThe expression level of Livin protein is elevated as the infiltration depth, differentiate extent, lymph node metastasis and clinical stages. On the depth of cancer infiltrating, the positive rates in T1+T2 was 33.33%, T3+T4 was 78.13% respectively. The comparison of the two showed significant difference (P<0.05). The comparison of the two showed significant difference (P<0.05). The poorly differentiated positive expression rate was 77.80%, the well and moderately differentiated positive expression rate was 43.50%. The comparison of the two showed significant difference (P<0.05). The group that the positive rates in lymph node transfer was 73.53%, the group that the positive rates in no lymph node transfer was 37.50% respectively. The stageⅠ+Ⅱwas 40.10%,Ⅲ+Ⅳwas 78.60% respectively, there were significant difference (P<0.05). The expression of Livin between age, gender, size, growth place and gross type had no significant difference (P>0.05).1.3 Correlations between expression of Livin protein and tumor chemotherapeutic sensitivityDetected by MTT method, all of the chemotherapeutics could inhibit the growth of tumor sells. The sensitivity rate to tumor cell were arranged in order were CDDP (37/50) >L-OHP (34/50)>5-FU(30/50)>VCR(29/50)>ADR(28/50)>CTX(26/50)>CPT-11(24/50)>MMC(22/50)>VP-16(19/50). The expressions of Livin protein have correlation with 5-FU, VCR, ADR and VP-16(P<0.05). Livin could effect the sensitivity of gastric cancer cells to 5-FU, VCR, ADR and VP-16.2 The results of Livin mRNA expression in gastric cancer tissues detected by reverse transcription polymerase chain reaction (RT-PCR)2.1 Exprssion of Livin mRNA in gastric cancer tissues The positive rates of Livin mRNA were 57.50% in gastric cancer tissues, but only 12.50% in normal gastric mucosa. The expressions of Livin mRNA in gastric carcinoma tissues were significantly higher (P<0.05).2.2 Correlations between the expression of Livin mRNA in gastric cancer tissues and clinical biological characteristicsThe expression level of Livin mRNA is elevated as the infiltration depth, differentiate extent, lymph node metastasis and clinical stages. On the depth of cancer infiltrating, the positive rates in T1+T2 was 22.22%, T3+T4 was 67.74% respectively. There were significant difference (P<0.05). The poorly differentiated positive expression rate was 77.80%, the well and moderately differentiated positive expression rate was 43.50%. The comparison of the two showed significant difference (P<0.05). The group that the positive rates in lymph node transfer was 70.00%, the group that the positive rates in no lymph node transfer was 20.00% respectively. There were significant difference (P<0.05). The stageⅠ+Ⅱwas 22.22%,Ⅲ+Ⅳwas 78.60% respectively, there were significant difference (P<0.05). The expression of Livin between age, gender, growth place and gross type had no significant difference (P>0.05).2.3 Correlations between expression of Livin mRNA and tumor chemotherapeutic sensitivityDetected by MTT method, all of the chemotherapeutics could inhibit the growth of tumor sells. The sensitivity rate to tumor cell were arranged in order were CDDP (26/40)>5-FU(26/40)>L-OHP(25/40)>ADR(18/40)>VCR(17/40)>CPT-11(16/40)>VP-16(15/40)>MMC(8/40)>CTX(7/40). The expressions of Livin protein have correlation with 5-FU, VCR, ADR and VP-16(P<0.05). Livin could effect the sensitivity of gastric cancer cells to 5-FU, VCR, ADR and VP-16.Conclusion:1 The positive rate of Livin protein in gastric cancer tissues was significantly higher than in normal gastric mucosa. It acts a role in course of formation of malignant tumors. Livin may act a new target for apoptosis-inducing therapy of gastric cancer.2 The expression of Livin protein correlated with infiltration depth, degrees of differentiation, lymph node metastases and grade, which may be useful in assessing the gastric cancer tissue malignancy extent and gastric cancer advance.3 The expression of Livin protein between age, gender, size, growth place and gross type had no significant difference (P>0.05).4 The expressions of Livin protein play an important role in the chemotherapy. Their detection can help us to select anticancer drugs, thus to implement Individualized chemotherapy.5 The positive rate of Livin mRNA in gastric cancer tissues was significantly higher than in normal gastric mucosa. Its expression was same with protein expression. It acts a role in course of formation of malignant tumors. Livin may act a new target for apoptosis-inducing therapy of gastric cancer.6 The expression of Livin mRNA correlated with infiltration depth, degrees of differentiation, lymph node metastases and grade, which may be useful in assessing the gastric cancer tissue malignancy extent and gastric cancer advance. Its expression was same with protein expression. 7 The expression of Livin mRNA between age, gender, size, growth place and gross type had no significant difference (P>0.05).8 The expressions of Livin mRNA play an important role in the chemotherapy. Their detection can help us to select anticancer drugs, thus to implement Individualized chemotherapy.