| Background: Gastric cancer is the leading cause of cancer-related deaths with high morbidity and mortality in China.Gastric cancer presents insidiously and routine gastroscopy screening rate is quite low in China, all of which contribute to the advanced stage of gastric cancer in most patients diagnosed.Cytotoxic platinum compound is considered the most important and first-line reference drug to be used in the chemotherapy for gastric cancer patients. However, intrinsic or acquired drug resistance to platinum leading to treatment failure is very common in clinical practice. Therefore, it is imperative to find a sensitive marker for the efficacy of platinum-based chemotherapy in the pursuit of individual chemotherapy in patients with gastric cancer.Micro RNAs(mi RNAs) is a class of non-coding small RNAs that mainly function to negatively regulate target gene m RNAs by degradation or inhibition of translation through complete or incomplete matching of 3’UTR of the target gene. Current studies indicated that mi R-192 was correlated with chemoresistance to platinum-based drugs in patients with pulmonary carcinoma, esophageal carcinoma and ovarian carcinoma. Furthermore, our study showed that mi R-192 expression level differed significantly in cell line SGC-7901 from that in SGC-7901/DDP and that its expression was strongly correlated with chemoresistance to platinum-based drugs in patients with gastric carcinoma. In this study, based on previous literature reports and our own studies, we aimed to explore the relationship between mi R-192 expression level in cancerous tissues and plasma and efficacy of platinum-based chemotherapy in patients with gastric cancer.Moreover,by investigating the relationship of mi R-192 expression levels between cancerous tissues and plasma, we provide the solid foundation for invidual chemotherapy, especially on the choice of platinum-based chemotherapy in patients with advanced gatric cancer.This study contains three parts.Part 1 On the correlation between mi R-192 expression in tumor tissues and the short-term efficacy of platinum-based chemotherapy in patients with advanced gastric carcinomaObjective To investigate the correlation of mi R-192 expression in the tumor tissues and the short-term efficacy of first-line platinum-based chemotherapy in the patients of advanced gastric carcinoma. Methods The mi R-192 expression was measured by real-time quantitative PCR in the tumor tissues in 44 patients with advanced gastric carcinoma and in the adjacent normal tissues from 20 patients. All the enrolled patients received platinum-based chemotherapy and the chemotherapeutic efficacy was evaluated. mi R-192 expression level in tumorous and non-tumorous component and its correlation with clinicopathological characteristics and platinum-based chemotherapy efficacy were evaluated. Results The mi R-192 expression was higher in the tumor tissues than adjacent normal tissues(t=2.104,P=0.049) and its level in carcinomatous component was statistically correlated with the presence of liver metastasis(t=2.282,P=0.041) while independent of age, sex, ECOG score, tumor grade and peritoneal metastasis(P>0. 05). Forty-four patients were considered evaluable for efficacy. There were PR in 11 cases, SD in 16 cases, and PD in 17 cases. ORR was 25% and DCR was 61.4%. mi R-192 expression level was positively correlated with chemotherapy efficacy(rs=0.600,P<0.05). Conclusion mi R-192 expression in the tumor tissues is correlated with the short-term chemotherapeutic efficacy of patients with advanced gastric carcinoma treated with platinum-based chemotherapy.Part 2 On the correlation between mi R-192 expression in plasma and the short-term efficacy of platinum-based chemotherapy in patients with advanced gastric carcinomaObjective To investigate the correlation of mi R-192 expression in plasma and the short-term efficacy of first-line platinum-based chemotherapy in the patients of advanced gastric carcinoma. Methods The mi R-192 expression was measured by real-time quantitative PCR in plasma samples from 50 patients with advanced gastric carcinoma and 20 patients with gastric benign disease. All the enrolled patients received platinum-based chemotherapy and the chemotherapeutic efficacy was evaluated. mi R-192 expression level in plasma and its correlation with clinicopathological characteristics and platinum-based chemotherapy efficacy were evaluated. Results The mi R-192 expression was higher in plasma samples from gastric cancer than gastric benign disease(t=3.288,P=0.033) and its level in patients with gastric cancer was statistically correlated with the presence of liver metastasis(t=1.194,P=0.035) while independent of age, sex, ECOG score, tumor grade and tumor location(P>0. 05). Fifty patients were considered evaluable for efficacy. There were PR in 10 cases, SD in 24 cases, and PD in 16 cases. ORR was 20% and DCR was 68%. mi R-192 expression level was positively correlated with chemotherapy efficacy(rs=0.565,P<0.05). Conclusion mi R-192 expression in plasma is correlated with the short-term chemotherapeutic efficacy of patients with advanced gastric carcinoma treated with platinum-based chemotherapy.Part 3 On the correlation between mi R-192 expression in plasma and tumor tissues in patients with advanced gastric carcinoma treated with platinum-based chemotherapy.Objective To investigate the correlation of mi R-192 expression in plasma and tumor tissues in patients with advanced gastric carcinoma treated with platinum-based chemotherapy. Methods We retrospectively analyzed the mi R-192 expression levels in the cancerous tissues and plasma samples of patients described in Part1 and Part2. Of these patients, mi R-192 expression levels in the cancerous tissues and plasma samples were measured in 35 cases. Correlation between mi R-192 expression levels in the cancerous tissues and plasma samples were evaluated using Pearson correlation analysis. Results mi R-192 expression was higher in tumor tissues than plasma samples,but no statistical difference(t=1.867,P=0.068). And mi R-192 expression in tumor tissues is positively correlated with its expression in plasma(r=0.751,P<0.05). Conclusion mi R-192 expression in tumor tissues is positively correlated with its expression in plasma. |
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