Aihemaijiang Kuerbanjiang1, Maimaitiyiming Maimaituerxun2, Yanjun Zhang3, Yiliang Li2, Gang Cui3, Aibaidula Abuduhabaier2, Abuduwaili Aierken2, Buya Miranbieke1, Meilikezati Anzaer4, Yusufu Maimaiti5. 1. Department of Gastroenterology, People's Hospital of Xinjiang Uygur Autonomous Region, Urumqi, 830000, China. 2. Department of General Surgery, People's Hospital of Xinjiang Uygur Autonomous Region, Urumqi, 830000, China. 3. Department of Clinical Research Center, People's Hospital of Xinjiang Uygur Autonomous Region, Urumqi, 830000, China. 4. Department of Gastroenterology, People's Hospital of Xinjiang Uygur Autonomous Region, Urumqi, 830000, China. anzar1204@sina.cn. 5. Department of General Surgery, People's Hospital of Xinjiang Uygur Autonomous Region, Urumqi, 830000, China. docyusufu@163.com.
Abstract
BACKGROUND: Esophageal cancer is one of the most aggressive malignancies, and is associated with multiple genetic mutations. At present, the v-Raf murine sarcoma viral oncogene homolog B1 (BRAF) gene mutation has been observed in esophageal cancer and is associated with poor prognosis. This study aimed to investigate the protein expression of BRAF in esophageal cancer and determine its effect on patient outcomes. METHODS: We used immunohistochemistry to detect the expression of BRAF via tissue microarrays in esophageal cancer samples, the Kaplan-Meier method to perform survival analysis, and the Cox proportional hazards regression model to explore the risk factors of esophageal cancer. The role of BRAF in the proliferation, invasion, and metastasis of esophageal cancer was studied by clone formation, scratch test, Transwell invasion and migration test. The tumor-bearing model of BRAF inhibitor was established using TE-1 cells, and corresponding negative control was set up to observe the growth rate of the two models. RESULTS: The results revealed that BRAF overexpression was significantly correlated with Ki67 (P < 0.05). Survival analysis showed that BRAF overexpression contributed to a shorter overall survival (P = 0.014) in patients with esophageal cancer. Univariate and multivariate regression analyses demonstrated that BRAF was a prognostic factor for poor esophageal cancer outcomes (P < 0.05). Small interfering RNA knockdown of BRAF significantly reduced the cell clone formation rate compared to the control group. Transwell assay analysis showed that the migration and invasion of cells in the experimental group were significantly inhibited relative to the control group, and the inhibition rates of the small interfering RNA group were 67% and 60%, respectively. In the scratch test, the wound healing ability of the BRAF knockdown group was significantly weaker than that of the control group. There were significant differences in tumor growth volume and weight between the two groups in nude mice. CONCLUSION: BRAF overexpression may serve as an effective predictive factor for poor prognosis.
BACKGROUND: Esophageal cancer is one of the most aggressive malignancies, and is associated with multiple genetic mutations. At present, the v-Raf murine sarcoma viral oncogene homolog B1 (BRAF) gene mutation has been observed in esophageal cancer and is associated with poor prognosis. This study aimed to investigate the protein expression of BRAF in esophageal cancer and determine its effect on patient outcomes. METHODS: We used immunohistochemistry to detect the expression of BRAF via tissue microarrays in esophageal cancer samples, the Kaplan-Meier method to perform survival analysis, and the Cox proportional hazards regression model to explore the risk factors of esophageal cancer. The role of BRAF in the proliferation, invasion, and metastasis of esophageal cancer was studied by clone formation, scratch test, Transwell invasion and migration test. The tumor-bearing model of BRAF inhibitor was established using TE-1 cells, and corresponding negative control was set up to observe the growth rate of the two models. RESULTS: The results revealed that BRAF overexpression was significantly correlated with Ki67 (P < 0.05). Survival analysis showed that BRAF overexpression contributed to a shorter overall survival (P = 0.014) in patients with esophageal cancer. Univariate and multivariate regression analyses demonstrated that BRAF was a prognostic factor for poor esophageal cancer outcomes (P < 0.05). Small interfering RNA knockdown of BRAF significantly reduced the cell clone formation rate compared to the control group. Transwell assay analysis showed that the migration and invasion of cells in the experimental group were significantly inhibited relative to the control group, and the inhibition rates of the small interfering RNA group were 67% and 60%, respectively. In the scratch test, the wound healing ability of the BRAF knockdown group was significantly weaker than that of the control group. There were significant differences in tumor growth volume and weight between the two groups in nude mice. CONCLUSION: BRAF overexpression may serve as an effective predictive factor for poor prognosis.
Authors: James Larkin; Michele Del Vecchio; Paolo A Ascierto; Ivana Krajsova; Jacob Schachter; Bart Neyns; Enrique Espinosa; Claus Garbe; Vanna Chiarion Sileni; Helen Gogas; Wilson H Miller; Mario Mandalà; Geke A P Hospers; Ana Arance; Paola Queirolo; Axel Hauschild; Michael P Brown; Lada Mitchell; Luisa Veronese; Christian U Blank Journal: Lancet Oncol Date: 2014-02-27 Impact factor: 41.316
Authors: Luping Lin; Saurabh Asthana; Elton Chan; Sourav Bandyopadhyay; Maria M Martins; Victor Olivas; Jenny Jiacheng Yan; Luu Pham; Mingxue Michelle Wang; Gideon Bollag; David B Solit; Eric A Collisson; Charles M Rudin; Barry S Taylor; Trever G Bivona Journal: Proc Natl Acad Sci U S A Date: 2014-02-03 Impact factor: 11.205