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OBJECTIVES: The pathological mechanisms of patients with Renal Cell Carcinoma (RCC) remain defined. This study aimed to evaluate relationships between the landscape of gene mutations and their clinical significance in RCC patients. METHODS: Tissue and peripheral blood samples of 42 patients with RCC were collected and performed for the Next Generation Sequencing (NGS) with Geneseeq PrimeTM 425-gene panel probes. Their landscapes of gene mutation were analyzed. We also carried out an evaluation of Tumor-Node-Metastasis (TNM) staging, RENAL nephelometry score, surgery, and targeted drug treatment of patients. Then we compared the correlations of landscape in gene mutations and the prognosis. RESULTS: The most common gene alternations, including BAP1, PBRM1, SETD2, CSF1R, NPM1, EGFR, POLE, RB1, and VHL genes, were identified in tissue and blood samples of 75% of patients. EGFR, POLE, and RB1 gene mutations frequently occurred in relapsed and metastatic patients. BAP1, CCND2, KRAS, PTPN11, ERBB2/3, JAK2, and POLE were presented in the patients with > 9 RENAL nephelometry score. Univariable analysis indicated that SETD2, BAP1, and PBRM1 genes were key factors for Disease-Free Survival (DFS). Multivariable analysis confirmed that mutated SETD1, NPM1, and CSF1R were critical factors for the Progression Free Survival (PFS) of RCC patients with target therapy. CONCLUSIONS: Wild-type PBRM1 and mutated BAP1 in patients with RCC were strongly associated with the outcomes of the patient. The PFS of the patients with SETD2, NPM1, and CSF1R mutations were significantly shorter than those patients without variants.

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Abstract Objectives The pathological mechanisms of patients with Renal Cell Carcinoma (RCC) remain defined. This study aimed to evaluate relationships between the landscape of gene mutations and their clinical significance in RCC patients. Methods Tissue and peripheral blood samples of 42 patients with RCC were collected and performed for the Next Generation Sequencing (NGS) with Geneseeq PrimeTM 425-gene panel probes. Their landscapes of gene mutation were analyzed. We also carried out an evaluation of Tumor-Node-Metastasis (TNM) staging, RENAL nephelometry score, surgery, and targeted drug treatment of patients. Then we compared the correlations of landscape in gene mutations and the prognosis. Results The most common gene alternations, including BAP1, PBRM1, SETD2, CSF1R, NPM1, EGFR, POLE, RB1, and VHL genes, were identified in tissue and blood samples of 75% of patients. EGFR, POLE, and RB1 gene mutations frequently occurred in relapsed and metastatic patients. BAP1, CCND2, KRAS, PTPN11, ERBB2/3, JAK2, and POLE were presented in the patients with > 9 RENAL nephelometry score. Univariable analysis indicated that SETD2, BAP1, and PBRM1 genes were key factors for Disease-Free Survival (DFS). Multivariable analysis confirmed that mutated SETD1, NPM1, and CSF1R were critical factors for the Progression Free Survival (PFS) of RCC patients with target therapy. Conclusions Wild-type PBRM1 and mutated BAP1 in patients with RCC were strongly associated with the outcomes of the patient. The PFS of the patients with SETD2, NPM1, and CSF1R mutations were significantly shorter than those patients without variants.

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OBJECTIVE: To explore the change in the expression of NT3 in the process of promoting the plasticity of spinal cord by acupuncture. METHODS: Five adult cats were subjected to unilateral spared root rhizotomy; their L1-L5, L7-S2 dorsal root ganglia (DRG) were sectioned, but L4 was spared. And two groups of acupoints [Zusani (St.36) and Xuanzhong (G. B.39); Futu (St.32) and Sanyingjiao (Sp.6)] located in hind limb were electro-stimulated for thirty minutes q.d. x 7. At seven days, after acupuncture, the L5 segment of spinal cord and spared dorsal root ganglion (L6) were taken and made into frozen section 20 microns in thickness. Immunohistochemistry (NT3 antibody 1:1500) and in situ hybridization (NT3 cRNA probe 1:100) techniques were used. The numbers of positive neuron for NT3 and it's mRNA in large, medium, small neuron of L6 DRG and the numbers of positive neurons and glia cells for NT3 in lamina II were counted respectively. RESULTS: The numbers of positive large, small neurons for NT3 and its mRNA in DRG and the number of positive neurons and glia cells for NT3 in lamina II on the acupuncture side increased apparently than those on the non-acupuncture side (P < 0.05). However, the positive signal of NT3 mRNA in lamina II was not seen in our study. CONCLUSION: The results indicate that acupuncture promoting the plasticity of spinal cord involves both the increase in expression of NT3 in large and small neurons of spared DRG and the increase in number of NT3 positive neurons and glia cells in spinal lamina II. Moreover, NT3 may play a role in the process of promoting the plasticity of spinal cord by acupuncture.

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OBJECTIVE: To investigate the spatiotemporal change rule of NGF, BDNF, NT-3 and their mRNA expression in spinal cord of cats after partial dorsal rhizotomy. METHODS: Rhizotomy of unilateral L1-L5, L7-S2 dorsal roots of cats was performed, leaving L6 as a spared dorsal root. By using ABC immunohistochemistry and in situ hybridization techniques, the dynamic changes of the above three factors and their mRNA in spinal lamina II of different segments were analysed. RESULTS: 1. In normal cat, NGF and it's mRNA were detected in part of neurons; BDNF, in nerve fiber terminals, varicosities and neurons; NT-3, in part of neurons, neuroglias and few nerve fiber terminals and varicosities. The mRNAs of the later two were negative. 2. The population of NGF and NGGmRNA positive neurons, NT-3 positive neurons and neuroglias increased significantly 3d-5d after rhizotomy. However, the quantity and density of positive varicosity of BDNF decreased. At 10-11d, the population of NGF and NGF mRNA positive neurons was still on the high level as that at 3-5d, and that of NT-3 began to decrease; the quantity of BDNF recovered to normal except for L, segment, but the density of positive varicosity of BDNF did not yet. The mRNAs of BDNF and NT-3 were still negative. 3. The change of each factor varied with the segments. The highest level time of NGF was earlier in L5, L6 than in L3; the recovery of the quantity of BDNF was the latest in L7; the change of NT-3 positive neuroglia was the same at each segment, but the number of NT-3 positive neuron in L5, L7 returned to normal at 10-11d, and that of L3 did not. CONCLUSION: The three factors all play roles in spinal plasticity after partial rhizotomy, but they function at different time phase and last different time length.

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