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1.
Eur J Endocrinol ; 184(4): 503-511, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33524004

RESUMO

Objective: Fusions involving neurotrophic tyrosine receptor kinase (NTRK) are known oncogenic drivers in a broad range of tumor types. It recently gained attention as a predictor of targeted therapy since selective NTRK inhibitors are now approved in the US and Europe for patients with solid tumors harboring gene fusions. However, estimation of NTRK gene fusion/alteration frequency and its clinicopathological characteristics in papillary thyroid cancer (PTC) is limited, especially in a population with high incidence for PTC like Middle Eastern population. This study aims to characterize the NTRK gene fusion frequency and investigate the utility of pan-Trk immunohistochemistry (IHC) as predictor of NTRK fusion in a large cohort of Middle Eastern PTC. Methods: FISH analysis for NTRK gene fusions and pan-Trk IHC was performed on 315 Middle Eastern PTCs. Correlation of NTRK gene fusion and protein expression with clinicopathological markers and patient outcome were determined. Results: In our cohort, 6.0% (19/315) patients showed NTRK gene fusions and were significantly associated with pediatric PTC (P = 0.0143), lymph node metastasis (P = 0.0428) and BRAF WT tumors (P < 0.0001). Pan-Trk IHC was positive in 9.2% (29/315) of cases and significantly associated with NTRK fusions, with a sensitivity of 73.7% and specificity of 94.9% in this cohort. Conclusions: This study confirms the presence of NTRK fusions in Middle Eastern PTC which is significantly enriched in BRAF WT as well as pediatric age group and proposes the usefulness of IHC to screen for PTC patients with NTRK fusion that might benefit from TRK inhibitors.


Assuntos
Fusão Gênica/genética , Glicoproteínas de Membrana/genética , Receptor trkA/genética , Receptor trkB/genética , Receptor trkC/genética , Câncer Papilífero da Tireoide/genética , Neoplasias da Glândula Tireoide/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Feminino , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Metástase Linfática/genética , Masculino , Pessoa de Meia-Idade , Proteínas Proto-Oncogênicas B-raf/genética , Arábia Saudita , Câncer Papilífero da Tireoide/química , Câncer Papilífero da Tireoide/patologia , Neoplasias da Glândula Tireoide/química , Neoplasias da Glândula Tireoide/patologia
2.
Int J Mol Med ; 47(4): 1, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33537835

RESUMO

Metastasis is the primary cause of the high mortality rates in head and neck squamous cell carcinoma (HNSCC). MicroRNA (miR)­411­5p has been discovered to serve an important role in cancer metastases. However, to the best of our knowledge, the association between miR­411­5p expression levels and HNSCC metastasis has not been thoroughly investigated. The present study aimed to research the function of miR­411­5p in HNSCC metastasis. The results of the present study revealed that miR­411­5p expression levels were upregulated in patients with HNSCC with lymph node metastasis and the upregulated expression levels of miR­411­5p were positively associated with the metastatic potential of HNSCC. Moreover, miR­411­5p promoted HNSCC cell migration, invasion and epithelial­mesenchymal transition (EMT). The results of the dual­luciferase reporter assays identified RING1 and YY1 binding protein (RYBP) as a functional downstream target gene for miR­411­5p. Therefore, whether miR­411­5p downregulated the expression levels of RYBP in HNSCC cells was subsequently investigated. Notably, the silencing of RYBP expression restored the stimulatory effects of miR­411­5p on HNSCC cell migration, invasion and EMT. In addition, the mRNA expression levels of miR­411­5p and RYBP were found to be inversely correlated in HNSCC samples. In conclusion, the results of the present study indicated that the miR­411­5p­mediated downregulation of RYBP expression levels may exert an important role in HNSCC metastasis and may provide a novel target for the treatment of HNSCC.


Assuntos
Metástase Linfática/genética , MicroRNAs/genética , Proteínas Repressoras/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Regulação para Cima/genética , Sequência de Bases , Linhagem Celular Tumoral , Movimento Celular/genética , Transição Epitelial-Mesenquimal/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Humanos , Metástase Linfática/patologia , Masculino , MicroRNAs/metabolismo , Pessoa de Meia-Idade , Invasividade Neoplásica , Metástase Neoplásica , Prognóstico , Proteínas Repressoras/genética
3.
Medicine (Baltimore) ; 100(6): e24674, 2021 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-33578599

RESUMO

BACKGROUND: Gastric cancer has multiple metastasis pathways, of which lymph node metastasis plays a dominant role. However, the specific mechanism of lymph node metastasis is still not unclear. METHODS: The bioinformatics technology was utilized to mine gene chip data related to gastric cancer and Epithelial-Mesenchymal Transition (EMT) in a high-throughput gene expression database (Gene Expression Omnibus, GEO), we screened out all genes that have differential expression levels in gastric cancer tissues and in adjacent normal gastric mucosa tissues. The corresponding function package of R language software were performed for gene annotation and cluster analysis, then enrichment analysis of genes with differential expression and protein interaction network diagram for correlation analysis were performed, we finally screened out the paired related homeobox 1 gene (PRRX1) related to EMT. Next, we collected 65 metastatic lymph node samples and 93 gastric cancer tissue samples. The expression levels of PRRX1 and EMT-related protein E-cadherin (E-ca) and vimentin (Vim) in gastric cancer tissues and metastatic lymph node tissues were determined by immunohistochemistry (IHC) staining of streptavidin-peroxidase (SP). The expression differences of PRRX1, E-ca and Vim in gastric cancer tissues and metastatic lymph node tissues as well as the correlation were analyzed by the experimental data, and the clinical significance was analyzed in combination with the clinicopathological data. RESULTS: The PRRX1 expression levels in gastric cancer tissues are significantly higher than that in adjacent normal gastric mucosa tissues. The positive expression rates of PRRX1, Vim and E-ca in gastric cancer and in metastatic lymph node tissues were significantly different. Comparing with that in gastric cancer, expression of PRRX1 and Vim was significantly down-regulated, and E-ca expression was significantly up-regulated in metastatic lymph nodes. CONCLUSION: PRRX1 may promote lymph node metastasis of gastric cancer by regulating EMT, and then affect the prognosis of patients. PRRX1 may be used as a new biological indicator to predict or prevent lymph node metastasis in gastric cancer.


Assuntos
Biomarcadores Tumorais/metabolismo , Transição Epitelial-Mesenquimal/genética , Proteínas de Homeodomínio/genética , Metástase Linfática/genética , Neoplasias Gástricas/secundário , Adulto , Idoso , Caderinas/metabolismo , Análise por Conglomerados , Biologia Computacional/métodos , Gerenciamento de Dados , Regulação para Baixo , Regulação Neoplásica da Expressão Gênica , Proteínas de Homeodomínio/metabolismo , Humanos , Metástase Linfática/patologia , Masculino , Pessoa de Meia-Idade , Peroxidase/metabolismo , Prognóstico , Neoplasias Gástricas/patologia , Estreptavidina/metabolismo , Regulação para Cima , Vimentina/metabolismo
4.
Cancer Sci ; 112(4): 1545-1555, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33484192

RESUMO

The anatomical spread of lymph node (LN) metastasis is of practical importance in the surgical management of colon cancer (CC). We examined the effect of KRAS, BRAF, and microsatellite instability (MSI) on LN count and anatomical spread pattern in stage III CC. We determined KRAS, BRAF, and MSI status from stage III CC patients. Biomarker status was correlated with LN count and anatomical spread pattern, which was classified as sequential or skipped. Relapse-free survival (RFS) was estimated using Kaplan-Meier method, and correlations were assessed using log-rank and Cox regression analyses. We analyzed 369 stage III CC patients. The proportion of KRAS mutant (mt), BRAF mt, and MSI-high (H) were 44.2% (163/344), 6.8% (25/344), and 6.8% (25/344), respectively. The mean number of metastatic LN was higher in microsatellite-stable (MSS) compared with MSI patients (3.5 vs. 2.7, P = .0406), although no differences were observed in accordance with KRAS or BRAF status. Interestingly, patients with BRAF mt and MSI-H were less likely to harbor skipped metastatic LN (9.3% vs 20% and 4% vs 10.5% compared with BRAF wild-type (wt) and MSS, respectively), but KRAS status did not predict anatomical spread pattern. Patients with KRAS wt and MSI-H showed superior RFS compared with KRAS mt and MSS patients, respectively, whereas BRAF status did not affect RFS. Differences exist in the anatomical pattern of invaded LN in accordance with the molecular status of stage III CC. Patients with MSI-H CC have less invaded and skipped LN, suggesting that a tailored surgical approach is possible.


Assuntos
Neoplasias do Colo/patologia , Metástase Linfática/patologia , Idoso , Biomarcadores Tumorais/genética , Neoplasias do Colo/genética , Feminino , Humanos , Metástase Linfática/genética , Masculino , Instabilidade de Microssatélites , Mutação/genética , Estadiamento de Neoplasias/métodos , Prognóstico , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas ras/genética
5.
Medicine (Baltimore) ; 99(50): e21789, 2020 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-33327221

RESUMO

X inactive specific transcript (XIST) is a novel long noncoding RNA (lncRNA) which has been reported to be frequently upregulated in various human cancer types and to function as an oncogene. It has been reported that the expression of lncRNA XIST was upregulated in non-small cell lung cancer (NSCLC). In the present study, we aimed to investigate the clinical significance and prognostic value of XIST in patients with NSCLC.A total of 156 pairs of NSCLC and corresponding adjacent normal lung tissue samples were obtained from NSCLC patients who had undergone surgery from July 2014 to March 2019. The Student's t test was used in different treated groups for statistical analysis. The association between XIST expression and clinicopathological features of NSCLC patients was evaluated using the chi-squared test. Survival curves were plotted using Kaplan-Meier method and compared by log-rank test.The expression of XIST was significantly higher in NSCLC samples compared to non-cancerous samples (P < .001). Statistically significant correlations were observed between high tissue XIST expression level and lymph node metastasis (P = .036) and high Tumor Node Metastasis (TNM) stage (P = .002). The log-rank test indicated that patients with increased XIST expression experienced poor overall survival (P = .006). Multivariate Cox regression analysis showed that XIST expression level (hazard ratio = 2.645, 95% confidence interval: 1.672-7.393, P = .029) was an independent factors in predicting the overall survival of NSCLC patients.The present study found that XIST expression level was significantly associated with advanced pathological stage and high TNM stage in NSCLC. Furthermore, upregulation of tissue lncRNA XIST predicts poor postoperative survival in patients with NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Neoplasias Pulmonares/patologia , RNA Longo não Codificante/genética , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/cirurgia , China/epidemiologia , Feminino , Humanos , Metástase Linfática/genética , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias/métodos , Período Pós-Operatório , Valor Preditivo dos Testes , Prognóstico , Análise de Sobrevida , Ativação Transcricional , Regulação para Cima/genética
6.
Medicine (Baltimore) ; 99(45): e23054, 2020 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-33157960

RESUMO

BACKGROUND: A growing number of studies have suggested that the Long intergenic noncoding RNA 00511 (LINC00511) is aberrantly expressed in multiple malignancies and is related to patient survival. Herein, we conducted a systematic review and meta-analysis to comprehensively evaluate the prognostic significance of LINC00511 in human malignancies. METHODS: Eligible studies published by March 11, 2020 were identified in 4 electronic databases including PubMed, EMBASE, Web of Science, and the Chinese National Knowledge Infrastructure. Hazard ratios and 95% confidence intervals (CIs) were used to evaluate the prognostic significance of LINC00511 expression in malignant tumors. The association between LINC00511 expression and cancer clinicopathologic features were assessed using Odds ratios (ORs) and CIs. RESULTS: A total of 13 studies, comprising 1,053 patients, were included in the meta-analysis. The calculated hazard ratio was 2.00 (95% CI: 1.59-2.52, P < .000), suggesting that higher LINC00511 expression could predict poorer overall survival in patients with malignancies. Additionally, our statistical analysis indicated that elevated LINC00511 expression closely associated with bigger tumors (OR = 2.92, 95% CI 1.65-5.18, P < .000), higher incidence of lymph node metastasis (OR = 3.46, 95% CI 2.11-5.66, P < .000) and distant metastasis (OR = 2.40, 95% CI 1.14-5.05, P = .02), poorer differentiation (OR = 1.55, 95% CI 1.11-2.16, P = .01), as well as more advanced TNM stage (OR = 3.90, 95% CI 2.70-5.63, P < .000). CONCLUSIONS: High LINC00511 expression may predict unfavorable prognosis in patients with malignancies. It should be further explored as a potential prognostic and therapeutic biomarker for human cancer.


Assuntos
Metástase Linfática/genética , Neoplasias/genética , RNA Longo não Codificante/genética , China/epidemiologia , Bases de Dados Factuais , Feminino , Humanos , Masculino , Estadiamento de Neoplasias/métodos , Neoplasias/mortalidade , Prognóstico , Projetos de Pesquisa , Taxa de Sobrevida
7.
Anticancer Res ; 40(10): 5405-5409, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32988860

RESUMO

AIM: To investigate the clinical significance of ATP-binding cassette transporter 11 (ABCC11) protein expression in colon cancer. MATERIALS AND METHODS: One hundred thirty nine patients with colon cancer resection between 2009 and 2011 were enrolled. The relationship with immunohistochemical ABCC11 staining and clinicopathological factors was retrospectively analyzed. RESULTS: Median age was 70 years including 67 males and 72 females. The patients with Stage 0, 1, 2, 3a and 4 were 4, 20, 43, 35, 7 and 30, respectively. The patients with curability (Cur) A, B and C were 109, 11 and 19, respectively. Positive expression of ABCC11 was observed in 31 patients (22.3%). There were no significant differences regarding age, gender, location, serum tumor markers, T category, lymphatic invasion and stage in relation to ABCC11 protein expression. Cases with node metastasis and venous invasion as well as unresectable cases were significantly more often found negative for ABCC11 protein (p=0.0246, 0.0285 and 0.0422, respectively). Concerning the 3 year disease free survival (DFS) and the 5 year overall survival (OS) in Stage 2/3 and in Stage 3 with adjuvant chemotherapy, no significant differences were found. However, OS in ABCC11 negative cases was 81.1%, which was significantly lower compared to positive cases, where OS was 96.2%. CONCLUSION: There was significant correlation with ABCC11 expression and lymph node metastasis, venous invasion and curability. The prognosis in ABCC11 negative cases was poor because of increased cases without curative resection.


Assuntos
Transportadores de Cassetes de Ligação de ATP/genética , Proliferação de Células/genética , Neoplasias do Colo/genética , Metástase Linfática/genética , Idoso , Neoplasias do Colo/patologia , Intervalo Livre de Doença , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Metástase Linfática/patologia , Masculino , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos
8.
Medicine (Baltimore) ; 99(39): e22105, 2020 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-32991406

RESUMO

BACKGROUND: Lymph node metastasis is a significant problem in breast cancer, and its underlying molecular mechanism is still unclear. The purpose of this study is to research the molecular mechanism and to explore the key RNAs and pathways that mediate lymph node metastasis in breast cancer. METHODS: GSE100453 and GSE38167 were downloaded from the Gene Expression Omnibus (GEO) database and 569 breast cancer statistics were also downloaded from the TCGA database. Differentially expressed miRNAs were calculated by using R software and GEO2R. Gene ontology and Enriched pathway analysis of target mRNAs were analyzed by using the Database for Database of Annotation Visualization and Integrated Discovery (DAVID) and R software. The protein-protein interaction (PPI) network was performed according to Metascape, String, and Cytoscape software. RESULTS: In total, 6 differentially expressed miRNAs were selected, and 499 mRNAs were identified after filtering. The research of the Kyoto Encyclopedia of Genes and Genomes (KEGG) demonstrated that mRNAs enriched in certain tumor pathways. Also, certain hub mRNAs were highlighted after constructed and analyzed the PPI network. A total of 3 out of 6 miRNAs had a significant relationship with the overall survival (P < .05) and showed a good ability of risk prediction model of over survival. CONCLUSIONS: By utilizing bioinformatics analyses, differently expressed miRNAs were identified and constructed a complete gene network. Several potential mechanisms and therapeutic and prognostic targets of lymph node metastasis were also demonstrated in breast cancer.


Assuntos
Neoplasias da Mama/genética , Metástase Linfática/genética , Biologia Computacional , Feminino , Regulação Neoplásica da Expressão Gênica , Redes Reguladoras de Genes , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Mapas de Interação de Proteínas , Microambiente Tumoral
9.
Hum Cell ; 33(4): 1133-1141, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32918700

RESUMO

The long non-coding RNA antisense 1 ADAMTS9-AS1 has been reported to predict the survival in several tumors, including bladder cancer and breast cancer. However, the clinical significance and biological behaviors of ADAMTS9-AS1 in colorectal cancer (CRC) have not been reported yet. In this study, the expression of ADAMTS9-AS1 was measured in CRC tissues and cell lines using quantitative real-time PCR analysis. The clinical significance of ADAMTS9-AS1 was evaluated with Chi-squared test, Kaplan-Meier method and Cox regression analysis in CRC patients. CCK8 assay, colony formation assay, flow cytometry and transwell assay were used to explore the biological function of ADAMTS9-AS1 knockdown in CRC cell lines (SW1116 and HT29). We further explore the role of ADAMTS9-AS1 in vivo though xenograft tumor assay. Our data showed that ADAMTS9-AS1 expression level was significantly up-regulated in CRC tissues and cell lines compared with corresponding controls. High ADAMTS9-AS1 level was associated with TNM stage, lymph node invasion and worse survival prognosis. Depletion of ADAMTS9-AS1 significantly suppressed cell proliferation, G1/S transition, migration and invasion, as well as suppressed CDK4/Cyclin D1 and epithelial-mesenchymal transition (EMT). To sum up, these findings illustrated that ADAMTS9-AS1 might be a promising therapeutic target and prognostic factor for CRC.


Assuntos
Proteína ADAMTS9/genética , Proteína ADAMTS9/metabolismo , Proliferação de Células/genética , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Transição Epitelial-Mesenquimal/genética , Expressão Gênica , Proteína ADAMTS9/fisiologia , Linhagem Celular Tumoral , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/fisiopatologia , Fase G1/genética , Humanos , Metástase Linfática/genética , Terapia de Alvo Molecular , Invasividade Neoplásica/genética , Estadiamento de Neoplasias , Prognóstico , Fase S/genética , Regulação para Cima/genética
10.
Medicine (Baltimore) ; 99(30): e21324, 2020 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-32791727

RESUMO

BACKGROUND: To systematically evaluate whether the expression level of long non-coding RNA activated by transforming growth factor-ß (lncRNA-ATB) is correlated with the prognosis of digestive system cancer (DSC) patients. METHODS: PubMed, Embase, Cochrane Library, Web of Science, Springerlink, Nature, and Karger databases were searched up to April 20, 2019 by 2 experienced researchers independently. The quality of studies was assessed with the Newcastle-Ottawa scale. The Review Manager 5.2 and STATA 12.0 software were used for this meta-analysis. RESULT: Eleven studies with 1227 DSC patients were included in the meta-analysis. Except for pancreatic cancer, high expression of lncRNA-ATB was associated with lymph node metastasis (risk ratio (RR) = 1.26, 95% confidence interval (CI): 1.12-1.42, P < .001), advanced clinical staging (RR = 1.44, 95%CI: 1.23-1.69, P < .001), reduced overall survival rate (OS) (hazard ratio (HR) = 2.33, 95%CI: 1.22-4.50, P = .01), and recurrence-free survival (RFS) (HR = 2.61, 95%CI: 1.46-4.65, P = .001) compared with low lncRNA-ATB expression in DSCs. CONCLUSIONS: High expression of lncRNA-ATB was significantly correlated with poor prognosis for most DSCs. The expression level of lncRNA-ATB could be a promising prognostic biomarker for DSC patients.


Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias do Sistema Digestório/genética , RNA Longo não Codificante/genética , Fator de Crescimento Transformador beta/genética , Idoso , Estudos de Casos e Controles , Neoplasias do Sistema Digestório/epidemiologia , Neoplasias do Sistema Digestório/mortalidade , Neoplasias do Sistema Digestório/patologia , Feminino , Humanos , Metástase Linfática/genética , Metástase Linfática/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Taxa de Sobrevida
11.
Hum Cell ; 33(4): 1281-1293, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32860589

RESUMO

The study aims to investigate how DANCR can alter the growth and metastasis of oral squamous cell carcinoma (OSCC) cells by regulating miR-216a-5p. The expression of DANCR and miR-216a-5p in OSCC patients and cells were measured. SCC15 and CAL-27 cells were selected to divide into Control, sh-NC, DANCR shRNA, DANCR, miR-216a-5p mimic, and DANCR + miR-216a-5p mimic groups. Dual-luciferase reporter gene assay was performed for the verification of the targeting relationship between miR-216a-5p and DANCR/Bcl-2/KLF12. We also quantified the abilities of OSCC cells regarding proliferation, invasion, migration and apoptosis, and the expression levels of apoptosis-related proteins were measured. Finally, the tumor-bearing nude mice were established to verify the effect of DANCR in vivo. Up-regulated DANCR expression and down-regulated miR-216a-5p expression were observed in both OSCC tissues and cells, and they were proven strongly correlated to the histological grade, clinical staging and lymph node metastasis of OSCC patients. Dual-luciferase reporter gene assay showed a target relationship between DANCR and miR-216a-5p, as well as between miR-216a-5p and Bcl-2/KLF12. Both DANCR shRNA and miR-216a-5p mimic decreased proliferative, migration and invasive abilities of OSCC cells with increased cell apoptosis. However, DANCR group showed completely opposite trends. Moreover, miR-216a-5p mimic could reverse the role of DANCR in promoting tumor growth. In-vivo experiment confirmed the inhibitory role of DANCR shRNA in tumor growth and metastasis. We concluded that DANCR may promote the growth and metastasis of OSCC cells and suppress OSCC cell apoptosis by sponging miR-216a-5p.


Assuntos
Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Regulação Neoplásica da Expressão Gênica/genética , Expressão Gênica/genética , MicroRNAs/genética , MicroRNAs/metabolismo , Neoplasias Bucais/genética , Neoplasias Bucais/patologia , RNA Longo não Codificante/genética , RNA Longo não Codificante/fisiologia , Apoptose/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Humanos , Fatores de Transcrição Kruppel-Like/genética , Fatores de Transcrição Kruppel-Like/metabolismo , Metástase Linfática/genética , Invasividade Neoplásica/genética , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , RNA Longo não Codificante/metabolismo
12.
Anticancer Res ; 40(8): 4557-4565, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32727786

RESUMO

BACKGROUND/AIM: Holocarboxylase synthetase (HLCS) catalyzes the specific attachment of biotin onto biotin-dependent carboxylases (BDCs) which play important roles in intermediary metabolism. Previous studies show that BDCs are overexpressed in many cancer types. However, expression of HLCS in cancerous tissues has not been reported. MATERIALS AND METHODS: Immunohistochemistry was used to investigate HLCS expression in breast tissue obtained from 65 Thai patients, and the correlation between its expression and key clinical-pathological parameters was assessed. The role of HLCS in supporting invasion was investigated in HLCS-knockdown MCF-7 cells. RESULTS: Overexpression of HLCS was significantly associated with metastasis of breast cancer cells to other lymph nodes but not the sentinel and axillary lymph nodes - a finding supported in cellular invasion assays using HLCS knockdown cells. Furthermore, overexpression of HLCS reduced survival time of patients with breast cancer. CONCLUSION: HLCS appears to be a prognostic marker for patients with breast cancer.


Assuntos
Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Carbono-Nitrogênio Ligases/genética , Metástase Linfática/genética , Mama/patologia , Linhagem Celular Tumoral , Feminino , Humanos , Linfonodos/patologia , Metástase Linfática/patologia , Células MCF-7 , Prognóstico
13.
Hum Cell ; 33(4): 1218-1228, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32578050

RESUMO

A number of kinesin proteins (KIFs) have been implicated in the development of multiple cancers. However, little is known about the expression and function of KIF15 in human breast cancer. Herein, we detected KIF15 expression in breast cancer tissues and paired adjacent normal tissues using immunohistochemistry and quantitative real-time polymerase chain reaction analysis, and the correlation of KIF15 expression with clinicopathological parameters was evaluated statistically. The role of KIF15 in cell proliferation, migration, tumor growth and metastasis of breast cancer cells was investigated in vitro and in vivo, and we explored potential molecular mechanisms underlying the effects of KIF15 in breast cancer through western blot analysis. The results revealed that increased KIF15 expression in breast cancer tissues were positively related with tumor size, lymph node metastasis and TNM stage, and higher KIF15 expression predicts a worse prognosis of patients with breast cancer. Furthermore, KIF15 knockdown markedly attenuated breast cancer cell proliferation, migration, tumor growth and metastasis in vitro and in vivo, and silenced KIF15 expression significantly inhibited the expression of phosphorylated AKT, phosphorylated JNK, and cyclin D1, while both p53 and p21 protein expressions were strongly enhanced. These results suggest that KIF15 is a potential oncogene in human breast cancer.


Assuntos
Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Movimento Celular/genética , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica/genética , Expressão Gênica/genética , Cinesina/genética , Feminino , Humanos , Cinesina/metabolismo , Metástase Linfática/genética , Metástase Linfática/patologia , Células MCF-7 , Estadiamento de Neoplasias , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo
14.
Immunol Med ; 43(3): 121-129, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32546118

RESUMO

The roles of interleukin-22 (IL-22) in carcinogenesis have been proposed in various neoplasms. Increased expression of IL-22 has been observed in oral squamous cell carcinoma (OSCC) lesions as well as in other cancers. OSCC is still associated with poor prognosis and a high mortality rate because of its invasiveness and frequent lymph node metastasis. In the present study, we investigated the effects of IL-22 on OSCC cells. The human OSCC cell lines Ca9-22 and SAS were stimulated with IL-22 (1-10 ng/mL), and their migration abilities were examined using a cell scratch assay. A Matrigel invasion assay was performed to evaluate the invasion abilities of OSCC cells. Signal transducer and activator of transcription 3 (STAT3) phosphorylation, matrix metalloproteinase (MMP) and epithelial-mesenchymal transition (EMT)-related genes and proteins were also examined. IL-22 treatment promoted the migration and invasion abilities of OSCC cells without increasing their viability. IL-22 stimulation also induced STAT3 phosphorylation, MMP-9 activity and EMT-related genes and proteins. Our findings suggest that IL-22 has possible roles in the development of OSCC.


Assuntos
Carcinoma de Células Escamosas/patologia , Movimento Celular/efeitos dos fármacos , Interleucinas/efeitos adversos , Interleucinas/fisiologia , Neoplasias Bucais/patologia , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Linhagem Celular Tumoral , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Transição Epitelial-Mesenquimal/genética , Expressão Gênica/efeitos dos fármacos , Expressão Gênica/genética , Humanos , Metástase Linfática/genética , Metaloproteinase 9 da Matriz/genética , Metaloproteinase 9 da Matriz/metabolismo , Neoplasias Bucais/genética , Neoplasias Bucais/metabolismo , Invasividade Neoplásica/genética , Fosforilação/genética , Fator de Transcrição STAT3/genética , Fator de Transcrição STAT3/metabolismo
15.
Cell Prolif ; 53(7): e12815, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32515024

RESUMO

Gastrointestinal tumours are tumours that originate in the digestive tract and have extremely high morbidity and mortality. The main categories include: oesophageal, gastric, and colorectal cancers. Circular RNAs are a new class of non-coding RNAs with a covalent closed-loop structure without a 5' cap or a 3' poly A tail, which can encode a small amount of polypeptide. Recent studies have shown that circRNAs are involved in multiple biological processes during the development of gastrointestinal tumours including proliferation, invasion and metastasis, radio- and chemoresistance, and inflammatory responses. Also, the clinical and pathological characteristics of the patient, such as staging and lymph node metastasis, are closely associated with the expression level of circRNAs. Further investigation of the function and the role of circRNAs in the development of gastrointestinal tumours will provide new directions for its clinical diagnosis and treatment.


Assuntos
Neoplasias Gastrointestinais/sangue , Neoplasias Gastrointestinais/genética , RNA Circular/sangue , RNA Circular/genética , Animais , Proliferação de Células/genética , Humanos , Inflamação/sangue , Inflamação/genética , Metástase Linfática/genética
16.
Medicine (Baltimore) ; 99(23): e20575, 2020 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-32502026

RESUMO

BACKGROUND: Recently, many studies have suggested that the aberrant expression of c-erbB-2 existed in oral cancer (OC) patients and had a correlation with poor clinical features across OC patients. Considering the inconsistent results among published articles, we performed the meta-analysis to assess the prognostic and clinical effect of c-erbB-2 expression on oral tumors. METHODS: Web of Science, Embase, and PubMed were retrieved to acquire relevant publications based on selection criteria, up to February 8, 2020. Pooled odds ratios (OR) and hazard ratios (HR) with 95% confidence intervals (CI) were applied to evaluate the associations between c-erbB-2 expression and overall survival (OS), disease specific survival, disease-free survival as well as clinicopathology of OC. RESULTS: A total of 30 literatures with 1499 patients for survival of OC were enrolled in this meta-analysis. The results indicated that c-erbB-2 overexpression was significantly associated with poor OS (HR = 2.40, 95% CI = 1.53-2.55, P < .05), disease specific survival (HR = 2.60, 95% CI = 1.11-4.10, P < .05) and disease-free survival (HR = 2.22, 95% CI = 1.46-2.99, P < .05). Subgroup analysis based on race showed that the significant prognostic value of c-erbB-2 in OC was found both in Caucasians and Asians (OS of Caucasians, HR = 2.90, 95% CI = 1.50-4.31, P < .05; OS of Asians, HR = 1.90, 95% CI = 1.27-2.53, P < .05). Moreover, OC patients with enhanced c-erbB-2 expression were prone to male (OR = 1.97, 95% CI = 1.22-3.19, P < .05), advanced TNM stage (OR = 1.84, 95% CI = 1.17-2.88, P < .05), lymph node metastasis (OR = 2.23, 95% CI = 1.47-3.36, P < .05) and advanced grade (OR = 1.98, 95% CI = 1.30-3.01, P < .05), but not associated with distant metastasis (OR = 1.65, 95% CI = 0.98-3.04, P > .05). CONCLUSIONS: c-erbB-2 may be a potential indicator in the prediction of prognosis and clinicopathological features in OC patients.


Assuntos
Neoplasias Bucais/genética , Receptor ErbB-2/metabolismo , Biomarcadores Tumorais/metabolismo , Intervalo Livre de Doença , Feminino , Regulação da Expressão Gênica , Humanos , Metástase Linfática/genética , Masculino , Neoplasias Bucais/mortalidade , Intervalo Livre de Progressão , Fatores Sexuais
17.
Oncology ; 98(7): 501-511, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32380498

RESUMO

INTRODUCTION: Anti-programmed cell death 1 (PD-1) therapies have shown promising clinical activity against gastric cancer (GC). We evaluated the clinical significance of immune-related gene expression in GC tissues to better understand the tumor immune microenvironment. METHODS: PD-1, PD-1 ligand 1 (PD-L1) and CD8 mRNA levels and clinicopathological factors, including survival, were examined by quantitative RT-PCR in 155 GC patients who underwent surgery. PD-1 and PD-L1 expression in tumor tissue from 24 GC patients was investigated by immunohistochemical analysis. RESULTS: PD-1, PD-L1 and CD8 mRNA levels were significantly lower in tumor tissue than in normal tissue (p < 0.0001, p < 0.05, and p < 0.0001). GC patients with low PD-1, PD-L1 and CD8 mRNA levels had significantly poorer overall survival (OS) than those with high PD-1, PD-L1 and CD8 mRNA levels, respectively (p < 0.001, p < 0.01 and p < 0.05). Low PD-1, PD-L1 and CD8 mRNA levels were more significantly associated with poor prognosis in undifferentiated-type GC patients than in differentiated-type GC patients (PD-1: differentiated p = 0.0071 vs. undifferentiated p = 0.0024; PD-L1: p = 0.6527 vs. p < 0.0001; CD8: p = 0.4465 vs. p < 0.05). Multivariate analysis showed that lymph node metastasis, peritoneal dissemination, distant metastasis, low PD-1 mRNA levels and low CD8 mRNA levels were independent prognostic factors for worse OS (low PD-1 mRNA level: OR 2.16, 95% CI 1.10-4.58, p < 0.05; low CD8 mRNA level: OR 2.55, 95% CI 1.12-6.90, p < 0.05). PD-1 and PD-L1 mRNA levels in immune cells were significantly associated with PD-1 and PD-L1 protein levels (both p < 0.05), respectively. CONCLUSIONS: PD-1, PD-L1 and CD8 mRNA levels may reflect antitumor immunity in GC, and low PD-1 and CD8 mRNA levels are potential predictive biomarkers for poor prognosis in GC patients who underwent surgery.


Assuntos
Antígeno B7-H1/genética , Antígenos CD8/genética , Expressão Gênica/imunologia , Receptor de Morte Celular Programada 1/genética , Neoplasias Gástricas/genética , Microambiente Tumoral/imunologia , Idoso , Antígeno B7-H1/metabolismo , Biomarcadores Tumorais/genética , Linfócitos T CD8-Positivos/imunologia , Feminino , Humanos , Metástase Linfática/genética , Masculino , Pessoa de Meia-Idade , Prognóstico , Receptor de Morte Celular Programada 1/metabolismo , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real
18.
Medicine (Baltimore) ; 99(19): e19957, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32384443

RESUMO

Studies of PDPN in cancers have focused on the interactions with palates through the binding with CECL-2 which mainly express on palates and immune cells, while little is known on its interactions with immune cells.PDPN expression in cancers was analyzed through Oncomine, GEPIA, and TIMER database. Prognostic value (HR, P value from log-rank test) was evaluated through Kaplan-Meier plotter and OncoLnc database. The correlations between PDPN and the infiltrating levels of immune cells in different cancers, and diverse immune markers in gastric cancer were investigated through TIMER database.High PDPN expression predicted poor overall survival (OS) and post-progression survival (PPS) particularly in gastric cancer (OS P = .0089; PPS P = .00085), especially among patients with Her-2 (+) and lymph node metastasis. In addition, PDPN was positively correlated with infiltrating levels of immune cells, other than B cells in gastric cancer. However, PDPN showed more correlations with immune markers of M2 type TAM (CD163, VSIG4, MS4A4A) and T cell exhaustion (TIM-3, TOX, and GZMB).These findings all suggest that high PDPN predicts poor survival outcomes, especially for Her-2 (+) gastric cancer patients. Though inducing M2 type TAM and T cell exhaustion, high PDPN can predict high levels of various immune cells infiltration in STAD. Those correlations may bring new ideas to immunology treatment for gastric cancer patients who do not benefit from the existing immune checkpoint inhibitors.


Assuntos
Linfócitos do Interstício Tumoral/metabolismo , Glicoproteínas de Membrana/imunologia , Glicoproteínas de Membrana/metabolismo , Neoplasias Gástricas/genética , Neoplasias Gástricas/imunologia , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/imunologia , Bases de Dados Factuais , Feminino , Humanos , Estimativa de Kaplan-Meier , Metástase Linfática/genética , Masculino , Prognóstico , Receptor ErbB-2/metabolismo , Neoplasias Gástricas/mortalidade
19.
Nat Genet ; 52(7): 692-700, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32451459

RESUMO

Genetic diversity among metastases is poorly understood but contains important information about disease evolution at secondary sites. Here we investigate inter- and intra-lesion heterogeneity for two types of metastases that associate with different clinical outcomes: lymph node and distant organ metastases in human colorectal cancer. We develop a rigorous mathematical framework for quantifying metastatic phylogenetic diversity. Distant metastases are typically monophyletic and genetically similar to each other. Lymph node metastases, in contrast, display high levels of inter-lesion diversity. We validate these findings by analyzing 317 multi-region biopsies from an independent cohort of 20 patients. We further demonstrate higher levels of intra-lesion heterogeneity in lymph node than in distant metastases. Our results show that fewer primary tumor lineages seed distant metastases than lymph node metastases, indicating that the two sites are subject to different levels of selection. Thus, lymph node and distant metastases develop through fundamentally different evolutionary mechanisms.


Assuntos
Neoplasias Colorretais/patologia , Metástase Linfática , Estudos de Coortes , Neoplasias Colorretais/genética , Progressão da Doença , Heterogeneidade Genética , Variação Genética , Humanos , Metástase Linfática/genética , Modelos Biológicos , Metástase Neoplásica/genética , Inoculação de Neoplasia , Filogenia
20.
Oncogene ; 39(22): 4358-4374, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32313227

RESUMO

Only a small number of genes are bona fide oncogenes and tumor suppressors such as Ras, Myc, ß-catenin, p53, and APC. However, targeting these cancer drivers frequently fail to demonstrate sustained cancer remission. Tumor heterogeneity and evolution contribute to cancer resistance and pose challenges for cancer therapy due to differential genomic rearrangement and expression driving distinct tumor responses to treatments. Here we report that intratumor heterogeneity of Wnt/ß-catenin modulator δ-catenin controls individual cell behavior to promote cancer. The differential intratumor subcellular localization of δ-catenin mirrors its compartmentalization in prostate cancer xenograft cultures as result of mutation-rendered δ-catenin truncations. Wild-type and δ-catenin mutants displayed distinct protein interactomes that highlight rewiring of signal networks. Localization specific δ-catenin mutants influenced p120ctn-dependent Rho GTPase phosphorylation and shifted cells towards differential bFGF-responsive growth and motility, a known signal to bypass androgen receptor dependence. Mutant δ-catenin promoted Myc-induced prostate tumorigenesis while increasing bFGF-p38 MAP kinase signaling, ß-catenin-HIF-1α expression, and the nuclear size. Therefore, intratumor δ-catenin heterogeneity originated from genetic remodeling promotes prostate cancer expansion towards androgen independent signaling, supporting a neomorphism model paradigm for targeting tumor progression.


Assuntos
Adenocarcinoma/patologia , Cateninas/fisiologia , Proteínas de Neoplasias/fisiologia , Neoplasias da Próstata/patologia , Transporte Ativo do Núcleo Celular , Adenocarcinoma/genética , Animais , Cateninas/genética , Linhagem Celular Tumoral , Núcleo Celular/ultraestrutura , DNA de Neoplasias/genética , Transição Epitelial-Mesenquimal/genética , Éxons/genética , Fator 2 de Crescimento de Fibroblastos/farmacologia , Genes myc , Xenoenxertos , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/fisiologia , Metástase Linfática/genética , Sistema de Sinalização das MAP Quinases , Masculino , Camundongos , Camundongos Transgênicos , Mutação , Proteínas de Neoplasias/genética , Neoplasias da Próstata/genética , Análise de Sequência de DNA , Frações Subcelulares/química , beta Catenina/fisiologia , Proteínas rho de Ligação ao GTP/fisiologia
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