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1.
Cancer Med ; 9(1): 179-193, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31724326

RESUMO

The current criteria for defining the recurrence risks of stage II colorectal cancer (CRC) are not robust; therefore, we aimed to explore novel gene signatures to predict recurrence risks and to reveal the underlying mechanisms of stage II CRC. First, the gene expression profiles of 124 patients with stage II CRC from The Cancer Genome Atlas (TCGA) database were obtained to screen differentially expressed genes (DEGs). A total of 202 DEGs, including 128 upregulated and 74 downregulated, were identified in the recurrence group (n = 24) compared to the nonrecurrence group (n = 100). Furthermore, the top 5 DEGs (ZNF561, WFS1, SLC2A1, MFI2, and PTGR1) were identified by random forest variable hunting, and four (ZNF561, WFS1, SLC2A1, and PTGR1) were selected to create a four-gene recurrent model (GRM), with an area under the curve (AUC) of 0.882 according to the receiver operating characteristic curve, and the robust diagnostic effectiveness of the GRM was further validated with another gene expression profiling dataset (GSE12032), with an AUC of 0.943. The diagnostic effectiveness of the GRM regarding recurrence was associated with poor disease-free survival in all stages of CRC. In addition, gene ontology functional annotation and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses revealed 18 enriched functions and 6 enriched pathways. Four genes, ABCG2, CACNA1F, CYP19A1, and TF, were identified as hub genes by the protein-protein interaction network, which further validated that these genes were correlated with a poor pathologic stage and overall survival in all stages of CRC. In conclusion, the GRM can effectively classify stage II CRC into groups of high and low risks of recurrence, thereby making up for the prognostic value of the traditional clinicopathological risk factors defined by the National Comprehensive Cancer Network guidelines. The hub genes may be useful therapeutic targets for recurrence. Thus, the GRM and hub genes could offer clinical value in directing individualized and precision therapeutic regimens for stage II CRC patients.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias Colorretais/genética , Recidiva Local de Neoplasia/epidemiologia , Transcriptoma/genética , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Biomarcadores Tumorais/antagonistas & inibidores , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Conjuntos de Dados como Assunto , Intervalo Livre de Doença , Regulação para Baixo , Seguimentos , Regulação Neoplásica da Expressão Gênica , Redes Reguladoras de Genes/efeitos dos fármacos , Humanos , Terapia de Alvo Molecular/métodos , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/prevenção & controle , Estadiamento de Neoplasias , Medicina de Precisão/métodos , Prognóstico , Mapas de Interação de Proteínas/efeitos dos fármacos , Mapas de Interação de Proteínas/genética , RNA-Seq , Curva ROC , Medição de Risco/métodos , Transcriptoma/efeitos dos fármacos , Regulação para Cima
2.
Zhongguo Gu Shang ; 32(6): 519-523, 2019 Jun 25.
Artigo em Chinês | MEDLINE | ID: mdl-31277534

RESUMO

OBJECTIVE: To analyze the displacement, stress and mechanism of lumbosacral joint disorder patients after bending and standing manipulation in the finite element model. METHODS: A three-dimensional finite element model of a patient with lumbosacral joint disorder was established. The finite element analysis method was used to observe and analyze the three loading conditions of the model:axial, 34 degree inclined upward and vertical upward. RESULTS: In the lumbosacral joint disorder model, the L5 vertebral body was concentrated in the middle of the lower endplate, the intervertebral disc was concentrated in the center of the intervertebral disc, and the stress of S1 and related structures were concentrated in the anterior and posterior edges of the vertebral body. After simulated manipulation, stress mainly concentrated in the anterior, posterior and central circular areas of L5 vertebral upper endplate. The posterior structures of vertebral body concentrated in the ventral part of pedicle, isthmus and dorsal part of lamina. The stress of intervertebral disc dispersed in the posterior edge of vertebral body. Displacement results:In the lumbosacral joint disorder model, the left transverse process, the upper and lower articular process and the left part of spinous process were significantly displaced to the left, and the intervertebral disc was protruded forward. After simulated manipulation, the lower notch of L5 vertebral body moved forward and upward; the area of intervertebral foramen increased; the inferior articular process of L5 vertebral body moved forward; the superior articular process of sacrum moved forward and downward; the distance of articular process joints increased; and the displacement of sacrum concentrated on the posterior edge of vertebral body and the median sacral crest. CONCLUSIONS: Successful lumbosacral joint modeling can be carried out by finite element analysis, and the mechanism of bending and erecting manipulation is clear, which is effective and safe for the treatment of lumbosacral joint disorders.


Assuntos
Disco Intervertebral , Vértebras Lombares , Fenômenos Biomecânicos , Análise de Elementos Finitos , Humanos , Região Lombossacral , Sacro
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