Yinting Chen1,2, Guoda Lian1,2, Guangsheng Ou3, Kege Yang1,2, Jianning Chen4, Haigang Li1,5, Shaojie Chen1,2, Jiajia Li1,2, Linjuan Zeng6, Kaihong Huang7,8. 1. Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, China. 2. Department of Gastroenterology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, China. 3. Department of Gastrointestinal Surgery, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510630, China. 4. Department of Pathology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510630, China. 5. Department of Pathology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, China. 6. Department of Oncology, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, 519000, China. zenglinj@mail.sysu.edu.cn. 7. Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, China. huangkh@mail.sysu.edu.cn. 8. Department of Gastroenterology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, China. huangkh@mail.sysu.edu.cn.
Abstract
BACKGROUND: B-cell-specific Moloney murine leukemia virus integration site 1 (Bmi-1) and Raf kinase inhibitory protein (RKIP) are involved in cancer metastasis and chemotherapeutic resistance, respectively. In this study, we evaluated the association between Bmi-1 and RKIP and outcome of gastric cancer through clinical data analysis and in vitro experiments. METHODS: Bmi-1 expression and RKIP expression were observed in 107 cases of gastric cancer through use of tissue microarray technology to identify their correlations with clinicopathological parameters, patient survival, and susceptibility to chemotherapy. The correlation was confirmed in gastric cancer cell lines, analyzed further by gene overexpression and silencing analysis, a cell invasion assay, and a chemosensitivity test. RESULTS: Positive expression of Bmi-1 was highly correlated with T classification and clinical stage. Diminished or lost expression of RKIP was significantly associated with T classification, lymph node metastasis, distant metastasis, and clinical stage. Bmi-1 is negatively and RKIP is positively related to patient survival. Positive expression of Bmi-1 and negative expression of RKIP are associated with poor patient survival and modest efficacy of postoperative chemotherapy. A meaningfully inverse association between Bmi-1 and RKIP was found in tissue microarray studies, and was verified further in gastric cancer cell lines. Moreover, gene overexpression and silencing analysis indicated that RKIP might be regulated by Bmi-1. Furthermore, the impacts of Bmi-1 on cell invasion and chemotherapy resistance were rescued by knockdown of RKIP. CONCLUSIONS: Our study implies that detection of Bmi-1 and RKIP is valuable in predicting patient survival and therapeutic response in gastric cancer, and the inverse association between Bmi-1 and RKIP reveals the potential molecular mechanisms underlying tumor metastasis and chemotherapy resistance.
BACKGROUND: B-cell-specific Moloney murine leukemia virus integration site 1 (Bmi-1) and Raf kinase inhibitory protein (RKIP) are involved in cancer metastasis and chemotherapeutic resistance, respectively. In this study, we evaluated the association between Bmi-1 and RKIP and outcome of gastric cancer through clinical data analysis and in vitro experiments. METHODS:Bmi-1 expression and RKIP expression were observed in 107 cases of gastric cancer through use of tissue microarray technology to identify their correlations with clinicopathological parameters, patient survival, and susceptibility to chemotherapy. The correlation was confirmed in gastric cancer cell lines, analyzed further by gene overexpression and silencing analysis, a cell invasion assay, and a chemosensitivity test. RESULTS: Positive expression of Bmi-1 was highly correlated with T classification and clinical stage. Diminished or lost expression of RKIP was significantly associated with T classification, lymph node metastasis, distant metastasis, and clinical stage. Bmi-1 is negatively and RKIP is positively related to patient survival. Positive expression of Bmi-1 and negative expression of RKIP are associated with poor patient survival and modest efficacy of postoperative chemotherapy. A meaningfully inverse association between Bmi-1 and RKIP was found in tissue microarray studies, and was verified further in gastric cancer cell lines. Moreover, gene overexpression and silencing analysis indicated that RKIP might be regulated by Bmi-1. Furthermore, the impacts of Bmi-1 on cell invasion and chemotherapy resistance were rescued by knockdown of RKIP. CONCLUSIONS: Our study implies that detection of Bmi-1 and RKIP is valuable in predicting patient survival and therapeutic response in gastric cancer, and the inverse association between Bmi-1 and RKIP reveals the potential molecular mechanisms underlying tumor metastasis and chemotherapy resistance.
Authors: W S Park; R R Oh; J Y Park; J H Lee; M S Shin; H S Kim; H K Lee; Y S Kim; S Y Kim; S H Lee; N J Yoo; J Y Lee Journal: Gastroenterology Date: 2000-09 Impact factor: 22.682
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