Assuntos
Carcinoma in Situ , Carcinoma de Células Escamosas , Ressecção Endoscópica de Mucosa , Doenças do Esôfago , Neoplasias Esofágicas , Carcinoma in Situ/diagnóstico por imagem , Carcinoma in Situ/cirurgia , Carcinoma de Células Escamosas/cirurgia , Neoplasias Esofágicas/diagnóstico por imagem , Neoplasias Esofágicas/cirurgia , Humanos , Resultado do TratamentoRESUMO
BACKGROUND: Colon adenocarcinoma (COAD) is one of the common gastrointestinal malignant diseases, with high mortality rate and poor prognosis due to delayed diagnosis. This study aimed to construct a prognostic prediction model for patients with colon adenocarcinoma (COAD) recurrence. METHODS: Differently expressed RNAs (DERs) between recurrence and non-recurrence COAD samples were identified based on expression profile data from the NCBI Gene Expression Omnibus (GEO) repository and The Cancer Genome Atlas (TCGA) database. Then, recurrent COAD discriminating classifier was established using SMV-RFE algorithm, and receiver operating characteristic curve was used to assess the predictive power of classifier. Furthermore, the prognostic prediction model was constructed based on univariate and multivariate Cox regression analysis, and Kaplan-Meier survival curve analysis was used to estimate this model. Furthermore, the co-expression network of DElncRNAs and DEmRNAs was constructed followed by GO and KEGG pathway enrichment analysis. RESULTS: A total of 54 optimized signature DElncRNAs were screened and SMV classifier was constructed, which presented a high accuracy to distinguish recurrence and non-recurrence COAD samples. Furthermore, six independent prognostic lncRNAs signatures (LINC00852, ZNF667-AS1, FOXP1-IT1, LINC01560, TAF1A-AS1, and LINC00174) in COAD patients with recurrence were screened, and the prognostic prediction model for recurrent COAD was constructed, which possessed a relative satisfying predicted ability both in the training dataset and validation dataset. Furthermore, the DEmRNAs in the co-expression network were mainly enriched in glycan biosynthesis, cardiac muscle contraction, and colorectal cancer. CONCLUSIONS: Our study revealed that six lncRNA signatures acted as an independent prognostic biomarker for patients with COAD recurrence.
Assuntos
Adenocarcinoma/patologia , Biomarcadores Tumorais/genética , Neoplasias do Colo/patologia , Regulação Neoplásica da Expressão Gênica , Modelos Estatísticos , Recidiva Local de Neoplasia/patologia , RNA Longo não Codificante/genética , Adenocarcinoma/genética , Idoso , Neoplasias do Colo/genética , Feminino , Seguimentos , Redes Reguladoras de Genes , Humanos , Masculino , Recidiva Local de Neoplasia/genética , Prognóstico , Taxa de SobrevidaRESUMO
BACKGROUND The RNA-seq FPKM data of 331 colorectal adenocarcinoma samples in The Cancer Genome Atlas database with matching clinical data were analyzed in order to reveal the prognostic value of m6A RNA methylation regulators in colon adenocarcinoma. MATERIAL AND METHODS The expression of 13 m6A RNA methylated regulators in samples were analyzed. The samples were classified into Cluster I and II by consistent clustering. The gene distribution was analyzed by principal component analysis. Further functional analysis of selected m6A RNA genes was performed and potential risk characteristics was developed using Lasso Cox regression algorithm. Using minimum criteria, the risk coefficients of YTHDF1 and HNRNPC were detected for Cluster II. Patients were divided into high-risk and low-risk subgroups based on the risk characteristics. The clinical data were analyzed by univariate and multivariate Cox regression analysis. RESULTS Expression of the detected m6A RNA methylated regulators except YTHDC2 in tumors were significantly different from their adjacent mucosa. Among them, only ALKBH5 and METTL4 were downregulated in tumors. The gene distribution between the 2 subgroups were different. The expression of m6A RNA methylation regulators including YTHDF1, HNRNPC, YTHDC2, YTHDC1, ZC3H13, and RBM15 were different between the 2 groups (P<0.05). The prognostic characteristics between the high-risk and low-risk groups were significant different (P<0.05), which had a good predictive significance of prognosis area under the curve (AUC)=0.62). Risk scores were less than 0.05, suggesting risk score was an independent prognostic factor for colon adenocarcinoma. CONCLUSIONS m6A RNA methylation regulators YTHDF1 and HNRNPC can be used as prognostic factors of colon cancer, which has potential value for colon cancer treatment.
Assuntos
Adenocarcinoma/metabolismo , Neoplasias do Colo/metabolismo , Metiltransferases/metabolismo , Adenocarcinoma/enzimologia , Adenocarcinoma/genética , Adenosina/metabolismo , Adenosina Trifosfatases/metabolismo , Algoritmos , Análise por Conglomerados , Colo/metabolismo , Neoplasias do Colo/enzimologia , Neoplasias do Colo/genética , Bases de Dados Genéticas , Perfilação da Expressão Gênica/métodos , Ribonucleoproteínas Nucleares Heterogêneas Grupo C/genética , Humanos , Metilação , Metiltransferases/genética , Análise Multivariada , Prognóstico , RNA/genética , RNA Helicases/genética , Proteínas de Ligação a RNA/genética , tRNA Metiltransferases/metabolismoRESUMO
BACKGROUND: Syndecan-1 (SDC-1) is a crucial membrane proteoglycan, which is confirmed to participate in several tumor cell biological processes. However, the biological significance of SDC-1 in colorectal carcinoma is not yet clear. An objective of this study was to investigate the role of SDC-1 in colorectal carcinoma cells. METHODS: Expression of SDC-1 in colorectal carcinoma tissues was evaluated by Reverse transcription-quantitative real-time PCR (RT-qPCR) and western blot. After transfection with pcDNA3.1 or pc-SDC-1, the transfection efficiency was measured. Next, SW480, SW620 and LOVO cell viability, apoptosis, migration and adhesion were assessed to explore the effects of exogenous overexpressed SDC-1 on colorectal carcinoma. In addition, the influences of aberrant expressed SDC-1 in Janus kinase 1 (JAK1)/signal transducer and activator of transcription 3 (STAT3) and rat sarcoma virus (Ras)/rapidly accelerated fibrosarcoma (Raf)/mitogen-activated protein kinase (MEK)/extracellular signal-regulated kinase (ERK) pathways were detected by western blot analysis. RESULTS: SDC-1 mRNA and protein levels were down-regulated in human colorectal carcinoma tissues. SDC-1 overexpression inhibited cell proliferation via suppressing CyclinD1 and c-Myc expression, meanwhile stimulated cell apoptosis via increasing the expression levels of B-cell lymphoma-2-associated x (Bax) and Cleaved-Caspase-3. Additionally, SDC-1 overexpression restrained cell migration via inhibiting the protein expression of matrix metallopeptidase 9 (MMP-9), and elicited cell adhesion through increasing intercellular cell adhesion molecule-1 (ICAM-1). Furthermore, SDC-1 overexpression suppressed JAK1/STAT3 and Ras/Raf/MEK/ERK-related protein levels. CONCLUSIONS: In general, the evidence from this study suggested that SDC-1 suppressed cell growth, migration through blocking JAK1/STAT3 and Ras/Raf/MEK/ERK pathways in human colorectal carcinoma cells.
Assuntos
Neoplasias Colorretais/patologia , Janus Quinase 1/metabolismo , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais , Sindecana-1/metabolismo , Quinases raf/metabolismo , Apoptose , Adesão Celular , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Expressão Gênica , Humanos , Sistema de Sinalização das MAP Quinases , Fosforilação , Sindecana-1/genética , Proteínas Supressoras de Tumor/genética , Proteínas Supressoras de Tumor/metabolismoRESUMO
The heterostructures of the ferromagnet (Cr2Te3) and topological insulator (Bi2Te3) have been grown by molecular beam epitaxy. The topological Hall effect as evidence of the existence of magnetic skyrmions has been observed in the samples in which Cr2Te3 was grown on top of Bi2Te3. Detailed structural characterizations have unambiguously revealed the presence of intercalated Bi bilayer nanosheets right at the interface of those samples. The atomistic spin-dynamics simulations have further confirmed the existence of magnetic skyrmions in such systems. The heterostructures of ferromagnet and topological insulator that host magnetic skyrmions may provide an important building block for next generation of spintronics devices.