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1.
Medicine (Baltimore) ; 99(2): e18533, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31914026

RESUMO

BACKGROUND: Recent studies have shown that long noncoding RNA (lncRNA) H19 is aberrantly expressed in various cancers. However, the prognostic significance of H19 in cancer patients remains to be elucidated. Here, we designed and conducted a meta-analysis to evaluate the prognostic value of this lncRNA for malignant solid neoplasms. METHODS: Relevant publications were collected from PubMed, Cochrane Library, Web of Science, and Embase databases. The relevant survival data of patients with H19-associated cancers were downloaded from The Cancer Genome Atlas (TCGA) project. Statistically significant relationships between H19 expression levels and overall survival were analyzed by hazard ratios (HRs) and corresponding 95% confidence intervals (CIs). RESULTS: A total of 15 studies with 1584 patients were ultimately included for this literature meta-analysis. An elevated level of H19 expression was found to be negatively correlated with the overall survival (OS) (HR = 1.62, 95% CI = 1.36-1.93, P < .001) in various cancers. Abnormal H19 expression was also positively correlated with poor tumor differentiation (P < .0001), more advanced clinical stage (P < .0001), earlier lymph node metastasis (P < .0001), and earlier distant metastasis (P < .05). The relationship between elevated H19 expression and overall survival was further validated by a TCGA dataset consisting of 7462 cancer patients (HR = 1.12, 95% CI = 1.03-1.22, P < .05). CONCLUSION: Our study indicates that H19 expression is closely relevant to clinical outcome and suggests that lncRNA H19 could be a crucial prognostic biomarker for certain carcinoma types.


Assuntos
Neoplasias/genética , Neoplasias/mortalidade , RNA Longo não Codificante/genética , Biomarcadores Tumorais/genética , Carcinoma , Feminino , Humanos , Metástase Linfática/genética , Metástase Linfática/patologia , Masculino , Neoplasias/patologia , Prognóstico , Intervalo Livre de Progressão
2.
Medicine (Baltimore) ; 99(4): e19011, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31977917

RESUMO

The aim of this study was to investigate the expression of Kif18A in cancerous and paracancerous tissues from 100 patients with nonsmall cell lung cancer (NSCLC).This was a prospective study of 100 patients with pathologically confirmed NSCLC (adenocarcinoma and squamous cell carcinoma [SCC], n = 50/group) that were operated at the Quanzhou First Hospital Affiliated to Fujian Medical University between June 2015 and December 2016. Kif18A protein expression in cancerous and paracancerous normal tissues was detected by western blot and immunohistochemistry.The expression of the Kif18A protein was higher in adenocarcinoma and SCC tissues than in the corresponding paracancerous normal tissues. The expression of the Kif18A protein was higher in highly differentiated tumors, in patients with lymph node metastasis (vs no lymph node metastasis), adenocarcinoma, and in stage III NSCLC. There were no associations between Kif18A expression and age, gender, and pathologic type.The expression of the Kif18A protein by immunohistochemistry was higher in NSCLC tissues than in normal tissues, and was associated with tumor differentiation, lymph node metastasis, and TNM staging. These results could provide a theoretical basis for novel molecular targeted therapies against NSCLC.


Assuntos
Adenocarcinoma/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma de Células Escamosas/genética , Cinesina , Neoplasias Pulmonares/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Metástase Linfática/genética , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
3.
Medicine (Baltimore) ; 98(50): e18370, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31852145

RESUMO

BACKGROUND: This study aims to assess the relationship between Rab1A expression and clinicopathological parameters and prognosis of patients with human solid cancer by summarizing the studies included. METHODS: PubMed, EMBASE, The Cochrane Library, and other sources were searched for relative studies. The risk ratios (RRs) and confidence interval (CI) were used to assess association between Rab1A expression and clinical parameters and prognosis in solid cancer patients. RESULTS: Eight studies were included in the final analysis with 800 patients. The results revealed that expression of Rab1A was significantly related with differentiation (RR = 0.883, 95%CI = 0.782-0.997, P = .044), lymph node metastasis (RR = 0.835, 95%CI = 0.753-0.926, P = .001), tumor-lymph node-metastasis (TNM) stage (RR = 1.190, 95%CI = 1.071-1.322, P < .001) and tumor size (RR = 0.818, 95%CI = 0.730-0.915, P < .001). What is more, no significant difference was seen in 1-year survival between high and low expression of Rab1A in multiple malignancies (RR = 0.855, 95%CI = 0.697-1.050, P = .136). However, increased Rab1A revealed poorer prognosis with 2-year survival (RR = 0.760, 95%CI = 0.701-0.824, P < .001), 3-year survival (RR = 0.669, 95%CI = 0.604-0.742, P < .001), 4-year survival (RR = 0.622, 95%CI = 0.554-0.698, P < .001) and 5-year survival (RR = 0.525, 95%CI = 0.458-0.698, P < .001). Expression of Rab1A was increased obviously in solid cancer tissues compared with the adjacent normal tissue (RR = 4.78, 95%CI 4.05-5.63, P = .015). CONCLUSION: This study revealed Rab1A expression links closely with tumor size, differentiation, lymph node metastasis, TNM stage and poor prognosis of human solid cancer patients. It may act as a biomarker of prognosis and a novel therapeutic target in solid cancer.


Assuntos
Metástase Linfática/genética , Proteínas rab1 de Ligação ao GTP/metabolismo , Biomarcadores Tumorais/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Estadiamento de Neoplasias
4.
Medicine (Baltimore) ; 98(48): e18031, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31770217

RESUMO

OBJECTIVE: Urothelial cancer-associated 1 (UCA1), an oncogenic long non-coding RNA, was aberrantly upregulated in colorectal cancer (CRC). This study aimed to further explore the clinical value of UCA1 in CRC. METHODS: Eligible studies were retrieved by searching Pubmed, Embase, Cochrane Library, Web of Science, Chinese National Knowledge Infrastructure, and Wanfang databases. Pooled hazard ratio (HR) and odds ratio (OR) with 95% confidence interval (CI) were applied to assess the prognostic role and clinical significance of UCA1. RESULTS: A total of 7 eligible studies with 775 cancer patients were recruited in the meta-analysis. The results showed that UCA1 overexpression was significantly correlated with poor overall survival in patients with CRC (HR = 2.25, 95% CI: 1.77-2.87, P < .001). There was also a significantly negative association between high UCA1 levels and tumor differentiation (OR = 2.84, 95% CI: 1.87-4.31, P < .001), lymph node metastasis (OR = 3.48, 95% CI: 2.24-5.41, P < .001), distant metastasis (OR = 2.67, 95% CI: 1.32-5.38, P = .006), tumor node metastasis stage (OR = 3.01, 95% CI: 2.16-4.18, P < .001), tumor invasion depth (OR = 2.18, 95% CI: 1.03-4.61, P = .04), and tumor size (OR = 2.27, 95% CI: 1.56-3.32, P < .001). CONCLUSIONS: Our study revealed that UCA1 overexpression was associated with poor prognosis and more advanced clinicopathological features, suggesting that UCA1 may serve as an indicator for unfavorable outcome of patients with CRC.


Assuntos
Neoplasias Colorretais/genética , RNA Longo não Codificante/metabolismo , Biomarcadores Tumorais/genética , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Intervalo Livre de Doença , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Metástase Linfática/genética , Invasividade Neoplásica/genética , Metástase Neoplásica/genética , Estadiamento de Neoplasias , Razão de Chances , Prognóstico , Modelos de Riscos Proporcionais , Carga Tumoral/genética , Regulação para Cima
5.
Indian J Pathol Microbiol ; 62(4): 549-555, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31611438

RESUMO

Context: C-Cbl is an important negative regulator of the cell signaling that acts as an adaptor protein and E3 ubiquitin ligase. The role of c-Cbl in development and regulation of human cancer has aroused intensive attention. Aims: In this study, we aimed to assess the correlation between the expression of c-Cbl and clinicopathological parameters and explored the role of c-Cbl in the development and progression of GC. Settings and Design: This is a Pilot study. Methods and Materials: In total, 84 tissue samples including 44 gastric cancers (GC) and 40 matched adjacent normal tissues were collected after surgery. Then tissue microarray (TMA) and immunohistochemistry (IHC) technology were combined to detect the protein expression of c-Cbl. Statistical Analysis Used: Statistical analysis was performed using SPSS 22.0 (IBM Corporation, Armonk, NY, USA). Results: We have studied the correlation between c-Cbl expression and clinicopathological parameters. Our study showed that c-Cbl has a low expression in 61.4% (27/44) of GC tissues, and the incidence of cases was significantly higher than that in adjacent normal tissues (P < 0.0001). In addition, the correlation between c-Cbl expression and gastric carcinoma subtype (P = 0.027), histological type (P = 0.033), Borrmann classification (P = 0.009), histological differentiation (P = 0.0005), lymph node metastasis (P = 0.007), and intravascular tumor thrombus (P = 0.036) has also been revealed. Conclusions: Our results show that c-Cbl is down-regulated in GC tissues compared with normal gastric tissue, which may play an important role in the development and progression of GC.


Assuntos
Desdiferenciação Celular , Metástase Linfática/genética , Proteínas Proto-Oncogênicas c-cbl/genética , Neoplasias Gástricas/genética , Idoso , Idoso de 80 Anos ou mais , Regulação para Baixo , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Projetos Piloto , Transdução de Sinais , Análise Serial de Tecidos
6.
Anticancer Res ; 39(10): 5623-5630, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31570459

RESUMO

BACKGROUND: This study aimed to investigate p16 and COX2 expression in oropharyngeal squamous cell carcinoma (OPSCC), and evaluate the prognostic role of COX2 expression under the new TNM classification. MATERIALS AND METHODS: Biopsy specimens obtained from 75 patients with OPSCC were stained for p16 and COX2 expression immunohistochemically. The results and clinical records were analyzed retrospectively. RESULTS: Fifty-nine patients (79%) were positive for p16. COX2 expression was correlated with poor relapse-free survival in patients overall, and in p16-positive patients. Smoking was positively associated with COX2 expression. Moreover, both positive COX2 expression and anterior wall tumor subsite were independently correlated with lymph node metastasis, which was the only independent prognostic factor in p16-positive OPSCC. CONCLUSION: The p16-positive rate in this study was comparable with that in the USA and Europe, and higher than that in other Asian countries. COX2 expression might affect the prognosis of p16-positive OPSCC through promoting lymph node metastasis.


Assuntos
Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Metástase Linfática/genética , Metástase Linfática/patologia , Neoplasias Orofaríngeas/genética , Neoplasias Orofaríngeas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Inibidor p16 de Quinase Dependente de Ciclina/genética , Ciclo-Oxigenase 2/genética , Intervalo Livre de Doença , Feminino , Humanos , Linfonodos/patologia , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/genética , Neoplasias Bucais/patologia , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias/métodos , Prognóstico , Estudos Retrospectivos , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia
7.
Medicine (Baltimore) ; 98(43): e17432, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31651846

RESUMO

BACKGROUND: Several studies have explored the prognostic value of stanniocalcin 2 (STC2) in various cancers, but obtained inconsistent results. Therefore, this meta-analysis was performed to determine the prognostic and clinicopathologic significance of STC2 in various cancers. METHODS: Eligible studies were identified by searching the online databases PubMed, Embase, Web of Science, and the China National Knowledge Infrastructure up to March 2019. Hazard ratios (HRs) with 95% confidence intervals (CIs) and were calculated to clarify the correlation between STC2 expression and prognosis of different cancers. Odds ratios (ORs) with 95% CI were selected to appraise the correlation between STC2 with clinicopathologic characteristics of patients with cancer. RESULTS: A total of 16 eligible studies with 4074 patients with cancer were included in our meta-analysis. The results showed that high STC2 expression can predict poor overall survival (OS) for cancer (HR = 1.48, 95% CI: 1.15-1.90, P = .002). Subgroup analysis found that high STC2 expression was associated with worse OS in Asian (HR = 1.85, 95% CI: 1.35-2.55), the reported directly from articles group (HR = 1.39, 95% CI: 1.05-1.84), survival curves group (HR = 1.93, 95% CI: 1.36-2.74), and gastric cancer (HR = 1.43, 95% CI: 1.04-1.95). Furthermore, high STC2 expression was significantly related to advanced T stage (OR = 1.83, 95% CI: 1.17-2.86, P = .008), lymph node metastasis (OR = 2.29, 95% CI: 1.51-3.45, P < .001), lymphatic invasion (OR = 2.15, 95% CI: 1.53-3.02, P < .001), venous invasion (OR = 1.97, 95% CI: 1.30-2.99, P = .001), and more advanced clinical stage (OR = 2.36, 95% CI: 1.74-3.19, P < .001) CONCLUSION:: Elevated expression of STC2 suggested a poor prognosis in patients with cancer and may serve as a new tumor marker to monitor cancer development and progression.


Assuntos
Glicoproteínas/sangue , Peptídeos e Proteínas de Sinalização Intercelular/sangue , Neoplasias/sangue , Neoplasias/mortalidade , Adulto , Idoso , Grupo com Ancestrais do Continente Asiático/genética , Biomarcadores Tumorais/sangue , Feminino , Humanos , Metástase Linfática/genética , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/genética , Estadiamento de Neoplasias , Neoplasias/patologia , Razão de Chances , Valor Preditivo dos Testes , Prognóstico , Modelos de Riscos Proporcionais , Neoplasias Gástricas/sangue , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia
8.
BMC Cancer ; 19(1): 957, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31615475

RESUMO

BACKGROUND: Circular RNAs (circRNAs) have emerged as a special subset of endogenous RNAs that are implicated in tumorigenesis and cancer progression. Herein we aim to carry out a meta-analysis to evaluate the clinicopathologic, diagnostic and prognostic significance of circRNA expression in colorectal cancer (CRC). METHODS: A systematic search of online databases was performed for original articles published in English, which investigated the diagnostic accuracy, prognostic utility, and clinicopathologic association of circRNA(s) in CRC. Data were strictly extracted and study bias was judged using the Quality Assessment for Studies of Diagnostic Accuracy II (QUADAS II) and Newcastle-Ottawa Scale (NOS) checklists. RESULTS: A total of 13 studies, involving 1430 patients with CRC, were included in the meta-analysis. The clinicopathologic study showed that abnormally expressed circRNAs were correlated with tumor diameter (P = 0.0350), differentiation (P = 0.0038), lymphatic metastasis (P = 0.0119), distant metastasis (P < 0.0001), TNM stage (P = 0.0002), and depth of invasion (P = 0.001) in patients with CRC. The summary area under the curve (AUC) of circRNA for the discriminative efficacy between patients with and without CRC was estimated to be 0.79, corresponding to a weighted sensitivity of 0.77 [95% confidence interval (CI): 0.74-0.79], specificity of 0.67 (95%CI: 0.64-0.70), and diagnostic odds ratio (DOR) of 7.52 (95%CI: 4.66-12.12). Survival analysis showed that highly expressed circRNAs were correlated with significantly worse overall survival (OS) [hazard ratio (HR) = 2.66, 95%CI: 2.03-3.50, P = 0.000; X2 = 4.34, P = 0.740, I2 = 0.0%], whereas lower expression of circRNAs was associated with prolonged OS (weighted HR = 0.30, 95%CI: 0.17-0.53, P = 0.000; X2 = 1.34, P = 0.909, I2 = 0.0%). Stratified analysis in circRNA expression status, and test matrix also showed robust results. CONCLUSION: Abnormally expressed circRNAs may be auxiliary biomarkers facilitating CRC diagnosis, and promising prognostic biomarkers in predicting the survival of CRC patients.


Assuntos
Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/genética , /genética , Área Sob a Curva , Biomarcadores Tumorais/genética , Neoplasias Colorretais/patologia , Expressão Gênica/genética , Humanos , Metástase Linfática/genética , Estadiamento de Neoplasias , Prognóstico , Modelos de Riscos Proporcionais , Viés de Publicação , Reação em Cadeia da Polimerase em Tempo Real , Sensibilidade e Especificidade , Análise de Sequência de RNA , Carga Tumoral/genética
9.
Medicine (Baltimore) ; 98(37): e17135, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31517852

RESUMO

RATIONALE: In estrogen receptor-positive HER2-negative (ER+HER2-) metastatic breast cancer, chemotherapy should be offered only to patients who develop endocrine resistance or have a rapid disease progression. However, the correct sequence of chemotherapy administration is still debated. PATIENT CONCERNS: We report the case of a 49-year-old woman with ER+ HER2- metastatic breast cancer who experienced an exceptionally long response to capecitabine administered as second-line therapy following a first-line anthracycline-based chemotherapy. DIAGNOSES: The patient was diagnosed with ER+ HER2- metastatic breast cancer with massive liver involvement and mediastinal lymph nodes metastasis. INTERVENTIONS: This patient was treated with capecitabine 1000 mg/mq bid given intermittently for 14 days within a 21-day cycle as a second-line therapy following a rapid progression on letrozole treatment given as a maintenance therapy. OUTCOMES: Our patient experienced a progression-free survival (PFS) >3 years with an exceptionally good quality of life (QoL). LESSONS: In ER+HER2- metastatic breast cancer patients, capecitabine monochemotherapy in second line may be associated with a particularly satisfactory PFS and no impact in terms of QoL. Future studies focused on biomarkers with predictive ability may help select patients who represent the best candidates to this treatment.


Assuntos
Antimetabólitos Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Capecitabina/uso terapêutico , Carcinoma Ductal de Mama/tratamento farmacológico , Carcinoma Ductal de Mama/patologia , Neoplasias da Mama/genética , Carcinoma Ductal de Mama/genética , Feminino , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/secundário , Metástase Linfática/genética , Pessoa de Meia-Idade , Receptores Estrogênicos/genética
10.
Int J Med Sci ; 16(8): 1089-1095, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31523170

RESUMO

Two common polymorphisms in the MTHFR gene, C677T and A1298C, are associated with reduced enzyme activity and may be associated with breast cancer susceptibility. We performed a case-control study to investigate the association between the two SNPs in the MTHFR gene and risk of breast cancer. In total, 58 breast cancer patients and 58 unaffected controls were enrolled in the study. Polymerase chain reaction/restriction fragment length polymorphism technique (PCR-RFLP) was conducted to determine the genotypes. No significant differences were found in the genotypes of the two polymorphisms of the MTHFR gene between cases and controls. The OR and 95% CI for the 677CC, 677CT and 677TT genotypes were 1.00, 0.95 (0.39-2.31) and 0.87 (0.27-2.80), respectively; those of the 1298AA, 1298AC and 1298CC genotypes were 1.00, 0.59 (0.26-1.36) and 0.78 (1.32-4.66) respectively. Furthermore, it has been shown in patients with breast cancer a risk of presenting with an aggressive biophenotype about twice or three times higher in the presence of the C677T and A1298C polymorphisms, respectively. Finally, the A1298Cpolymorphism is significantly associated with increased recurrence risk of lymph node-positive breast cancer. Our study has not shown a significant association between MTHFR gene polymorphisms and breast cancer risk. However, it highlighted the key-role played by the presence of mutant alleles for both polymorphisms in increasing the risk of developing more aggressive phenotypes; moreover, specifically in A1298C, it might also lead to a higher risk of developing lymph node metastasis.


Assuntos
Neoplasias da Mama/genética , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Polimorfismo de Nucleotídeo Único , Adulto , Idoso , Índice de Massa Corporal , Neoplasias da Mama/patologia , Estudos de Casos e Controles , Feminino , Predisposição Genética para Doença , Humanos , Itália , Metástase Linfática/genética , Pessoa de Meia-Idade
11.
Pathol Res Pract ; 215(10): 152567, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31383535

RESUMO

OBJECTIVE: This paper aims to provide some experimental basis for unveiling the role of PDRG1 (P53 And DNA Damage-Regulated Gene 1) gene silencing in the growth and development of gastric cancer. METHODS: PDRG1 levels in gastric cancer tissues and cell lines were measured by Western blotting. Then, gastric cancer BGC-823 cells, divided into Control, PDRG1 siRNA, NC siRNA and PDRG1 siRNA + KU55933 (ATM inhibitor) groups, were used to conduct a series of in vitro experiments including MTT, Flow cytometry, Wound-healing and Transwell assays. Expression of PDRG1 and ATM/p53 pathway-related proteins were determined by Western blot. Eventually, experiment in vivo was carried out to verify the control of PDRG1 on gastric cancer cells after establishing the tumor xenograft model in nude mice. RESULTS: PDRG1 was significantly elevated in gastric cancer tissues and was associated with lower cell differentiation degree, more severe lymph node metastasis and higher tumor stage of gastric cancer patients. The growth of BGC-823 cells were significantly retarded and the cell apoptosis was increased in the PDRG1 siRNA group; besides, cell cycle was arrested in G2/M phase, and the expressions of p-ATM, p53, p21, p-cdc2 and cleaved caspase-3 were up-regulated with the reduced PDRG1. However, KU55933 could reverse the anti-tumor effect of PDRG1 siRNA on BGC-823 cells. The in-vivo experiment confirmed PDRG1 siRNA can inhibit tumor xenograft growth in nude mice. CONCLUSION: Specific PDRG1 gene silencing may inhibit the growth and metastasis of gastric cancer cells through the activation of ATM/p53 pathway.


Assuntos
Apoptose/genética , Proteínas de Ligação a DNA/genética , Inativação Gênica , Neoplasias Gástricas/genética , Estômago/patologia , Adulto , Animais , Pontos de Checagem do Ciclo Celular/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Feminino , Humanos , Metástase Linfática/genética , Metástase Linfática/patologia , Masculino , Camundongos , Camundongos Nus , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Transdução de Sinais/genética , Neoplasias Gástricas/patologia
12.
Cancer Sci ; 110(10): 3368-3374, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31432574

RESUMO

BRCA1/2 genes are the most frequently germline mutated DNA-repair genes, and the survival of BRCA1/2 carriers has been extensively explored in breast cancer. However, the prevalence of germline mutations in non-BRCA1/2 DNA-repair genes and the survival of carriers are largely unknown in a large cohort of unselected breast cancer patients. Germline mutations in 16 DNA-repair genes were determined using a multigene panel in 7657 BRCA1/2-negative breast cancer patients who were unselected for family history of cancer or age at diagnosis. Among the 7657 BRCA1/2-negative breast cancer patients, 257 (3.4%) carried at least 1 pathogenic germline mutation in the 16 DNA-repair genes. The prevalence of DNA-repair gene mutations was significantly higher in familial breast cancers (5.2%, P = 0.002) and early-onset breast cancers (diagnosed at and before the age of 40) (4.5%, P = 0.003) than that of sporadic breast cancers (2.9%) (diagnosed above age of 40), respectively. The DNA-repair gene mutation carriers were significantly more likely to have a larger tumor (P = 0.04) and axillary lymph node metastasis (P = 0.03). Moreover, DNA-repair gene mutation was an independent unfavorable factor for recurrence-free survival (adjusted hazard ratio [HR] = 1.38, 95% CI: 1.00-1.91, P = 0.05) and disease-specific survival (adjusted HR=1.63, 95% CI: 1.04-2.57, P = 0.03) in this cohort. Overall, 3.4% of BRCA1/2-negative breast cancer patients carried germline mutations in the 16 DNA-repair genes, and the DNA-repair gene mutation carriers exhibited an aggressive phenotype and had poor survival compared with noncarriers.


Assuntos
Neoplasias da Mama/patologia , Reparo do DNA , Mutação em Linhagem Germinativa , Metástase Linfática/patologia , Análise de Sequência de DNA/métodos , Adulto , Idade de Início , Idoso , Idoso de 80 Anos ou mais , Proteína BRCA1/genética , Proteína BRCA2/genética , Neoplasias da Mama/genética , Neoplasias da Mama/mortalidade , Feminino , Predisposição Genética para Doença , Humanos , Metástase Linfática/genética , Pessoa de Meia-Idade , Análise de Sobrevida , Carga Tumoral , Adulto Jovem
13.
Zhonghua Zhong Liu Za Zhi ; 41(8): 594-598, 2019 Aug 23.
Artigo em Chinês | MEDLINE | ID: mdl-31434450

RESUMO

Objective: To explore the molecular characteristics of follicular variant papillary thyroid carcinoma (FVPTC), follicular thyroid adenoma (FTA) and follicular thyroid carcinoma (FTC), and investigate their role in tumorigenesis, differential diagnosis and prognosis evaluation in patients with follicular thyroid neoplasm. Methods: We retrospectively analyzed 50 surgical resection samples of follicular thyroid neoplasm. DNA was obtained from formalin-fixed, paraffin-embedded tissue, and subjected to next-generation sequencing (NGS) to analyze 50 hotspots for mutation in genes. Results: 47 samples passed quality control, including 29 FVPTCs, 8 FTAs and 10 FTCs. 75.9% of FVPTCs harbored mutated genes: BRAF V600E (31.0%, 9/29) was the most frequent, followed by TP53 (27.6%, 8/29), and N/KRAS (20.7%, 6/29). In contrast, 37.5% (3/8) FTAs carried NRAS Q61R mutation with 12.5% (1/8) FTA carrying mutated BRAF G466E. 20% (2/10) FTCs harbored NRAS Q61R mutation, and 20% (2/10) FTCs with TP53 mutations. BRAF V600E gene mutation only appeared in FVPTC, and was associated with age of onset and lymph node metastasis. There was no significant correlation between N/KRAS mutations and clinical pathologic features. Patients with lymph node metastasis group seems to have more TP53 mutation. Conclusions: BRAF V600E gene mutation can be used to identity FVPTC from FTA/FTC. N/KRAS mutations cannot be used as the exclusive indicator of benign and malignant in thyroid follicular tumor. TP53 mutations play an important role in the process of follicular thyroid neoplasm, indicating more aggressive behavior and poor prognosis.


Assuntos
Adenocarcinoma Folicular/genética , Adenocarcinoma Folicular/patologia , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/patologia , Humanos , Metástase Linfática/genética , Mutação , Estudos Retrospectivos , Proteína Supressora de Tumor p53/genética
14.
Technol Cancer Res Treat ; 18: 1533033819858668, 2019 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31315522

RESUMO

OBJECTIVE: To identify the expression of kinetochore scaffold 1 (KNL1) in colorectal tumor tissues and to clarify the role of this gene in the proliferation capability of colorectal cancer cells. METHODS: A total of 108 paired colorectal tumor and normal tissue samples were collected from patients with colorectal cancer and subjected to quantitative polymerase chain reaction and immunohistochemistry analyses. Expression levels of KNL1 mRNA and protein were compared between tumor and normal tissues, and KNL1 levels were evaluated in relation to the patients' tumor differentiation, sex, lymph node metastasis, TNM stage, infiltration depth, age, and tumor location. Survival curves were also constructed and compared between patients with tumor samples with and without KLN1 protein expression. KNL1 was under-expressed in colorectal cancer cells in vitro using lentiviral transfection with short hairpin RNA, and its function was evaluated by proliferation, colony-formation, and apoptosis assays. Expression levels of BUB1 protein were also compared between tumor and normal tissues, and the correlation between KNL1 expression and BUB1 expression in colorectal cancer tissues was examined. RESULTS: KNL1 mRNA and protein were both highly expressed in colorectal tumor tissues compared with paired normal tissues. KNL1 downregulation significantly inhibited colorectal cancer cell proliferation and colony formation, and promoted apoptosis. KNL1 protein expression was significantly associated with tumor differentiation, but not with sex, lymph node metastasis, TNM stage, infiltration depth, age, or tumor location. KNL1 protein expression was also significantly associated with poorer survival. Moreover, there was a significant correlation between KNL1 and BUB1 in colorectal cancer tissues. CONCLUSIONS: KNL1 plays an effective role in decreasing apoptosis and promoting the proliferation of colorectal cancer cells, suggesting that its inhibition may represent a promising therapeutic approach in patients with colorectal cancer.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias Colorretais/genética , Proteínas Associadas aos Microtúbulos/genética , Proteínas Serina-Treonina Quinases/genética , Apoptose , Diferenciação Celular/genética , Movimento Celular/genética , Proliferação de Células/genética , Neoplasias Colorretais/patologia , Intervalo Livre de Doença , Feminino , Regulação Neoplásica da Expressão Gênica , Células HCT116 , Humanos , Metástase Linfática/genética , Metástase Linfática/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico
15.
J Exp Clin Cancer Res ; 38(1): 314, 2019 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-31315643

RESUMO

BACKGROUND: IDO1 (Indoleamine 2,3-dioxygenase 1) inhibits host anti-tumor immune response by exhausting tryptophan in tumor microenvironment, but the pathogenic mechanisms of IDO1 in gastric cancer (GC) cells need to be further explored. METHODS: The aim of this study was to use CCLE (Cancer Cell Line Encyclopedia) transcriptomic data of GC cell lines for WGCNA (Weighted Gene Co-expression Network Analysis) analysis, and explore the potential functions and mechanisms of IDO1 in GC progression in vitro and in vivo. RESULTS: The higher expression level of IDO1 was identified in 4 out of 7 GC cell lines. Increased IDO1 expression strongly promoted cell migration via its metabolite kynurenine and was associated with pathways of immune activation according to GSEA (Gene Set Enrichment Analysis). The functions of IDO1 were closely associated with extracellular matrix, collagen metabolic and catabolic process by WGCNA analysis. Among five hub genes (AXL, SGCE, COL12A1, ANTXR1, LOXL2), COL12A1 and LOXL2 were upregulated in GC tissues. IDO1 disclosed positive correlation with six collagen genes by coefficient matrix diagram. Knockdown of IDO1 decreased the expression of LOXL2, COL6A1, COL6A2 and COL12A1 in GC cells in both mRNA and protein levels. Of them, knockdown of COL12A1 inhibited cell migration more apparently than knockdown of others. IDO1 and COL12A1 revealed synergistic efficacy on promoting cell migration via a positive feedback sustained by MAPK pathway. This bioprocess was mediated by IDO1 metabolite kynurenine and integrin ß1. A popliteal lymph nodemetastasis model was established for verifying metastatic promotion of IDO1 and COL12A1 in GC. CONCLUSIONS: IDO1 and COL12A1 synergistically promoted GC metastasis. The novel findings suggested that both IDO1 and COL12A1 may be promising targets on anti-cancer treatment in GC.


Assuntos
Colágeno Tipo XII/metabolismo , Indolamina-Pirrol 2,3,-Dioxigenase/metabolismo , Cinurenina/metabolismo , Metástase Linfática/patologia , Neoplasias Gástricas/patologia , Animais , Linhagem Celular Tumoral , Movimento Celular , Colágeno Tipo XII/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Indolamina-Pirrol 2,3,-Dioxigenase/genética , Metástase Linfática/genética , Sistema de Sinalização das MAP Quinases , Camundongos , Transplante de Neoplasias , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Microambiente Tumoral , Regulação para Cima
16.
Mol Cell Biochem ; 460(1-2): 93-103, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31278587

RESUMO

Nicotinamide N-methyltransferase (NNMT) is an important methyltransferase involved in the biotransformation of many drugs and exogenous compounds. Abnormal expression of NNMT protein is closely associated with the onset and progression of many malignancies, but little is known about its role in esophageal squamous cell carcinoma (ESCC). Therefore, we aimed to explore whether NNMT plays any roles in carcinogenesis and metastasis in ESCC. NNMT expression was determined by immunohistochemistry in ESCC and corresponding adjacent normal tissues. Functional experiments were performed to elucidate the effects of NNMT knockdown on the proliferation, apoptosis, cell cycle, migration, and epithelial-mesenchymal transition (EMT) in EC9706 and TE1 cells. NNMT expression was significantly elevated in ESCC tissues compared with corresponding adjacent normal tissues. Moreover, a significant association emerged between NNMT expression and lymph node metastasis. SiRNA-mediated knockdown of NNMT in ESCC cells can significantly suppress cell viability and migration, induce cell cycle arrest, and promote cell apoptosis. In addition, NNMT downregulation led to the reversal of EMT, as reflected by upregulation of the intercellular adhesion molecule E-cadherin and downregulation of the mesenchymal markers N-cadherin and Vimentin. Further study found that NNMT knockdown suppressed the Wnt/ß-catenin signaling pathway. Taken together, these findings indicate that NNMT is a critical regulator of EMT in ESCC and may be a potential therapeutic target for ESCC metastasis.


Assuntos
Movimento Celular/genética , Regulação para Baixo , Transição Epitelial-Mesenquimal/genética , Carcinoma de Células Escamosas do Esôfago/genética , Carcinoma de Células Escamosas do Esôfago/patologia , Nicotinamida N-Metiltransferase/genética , Via de Sinalização Wnt , Idoso , Idoso de 80 Anos ou mais , Apoptose/genética , Pontos de Checagem do Ciclo Celular/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Sobrevivência Celular/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Metástase Linfática/genética , Metástase Linfática/patologia , Masculino , Pessoa de Meia-Idade , Nicotinamida N-Metiltransferase/metabolismo , RNA Interferente Pequeno/metabolismo
17.
Int J Med Sci ; 16(6): 774-782, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31337950

RESUMO

The purposes of this study were to examine whether there were associations among matrix metalloproteinase-11 (MMP-11) gene polymorphisms, development and clinicopathological characteristics of uterine cervical cancer as well as patient survival or not. Five single-nucleotide polymorphisms (SNPs) of the MMP-11 gene rs738791, rs738792, rs2267029, rs28382575, and rs131451 from one hundred and thirty patients with invasive cancer, 99 patients with high-grade cervical intraepithelial neoplasia (CIN) of uterine and 335 normal controls were analyzed using real-time polymerase chain reaction. Our results revealed that genotypic frequencies of CT/TT in MMP-11 SNP rs738791, with CC as a reference, tended to exhibit significantly different distributions (p=0.044, AOR: 0.63, 95% CI: 0.41-0.99) between patients with cervical invasive cancer and normal control women when controlling age. After multiple significance adjustment, the tendency becomes insignificant (Holm's adjusted p 0.176). Although CT/TT genotype of MMP-11 gene rs738791 tended to increase the risk of developing stage II disease at least (p=0.035; OR: 2.16, 95% CI: 1.05-4.44) and deep stromal invasion more than 10 mm (p=0.043; OR: 2.08, 95% CI: 1.02-4.26) with CC as a reference in patients with uterine cervical cancer. They became insignificant after multiple significance adjustment and the Holm's adjusted p values would become as 0.245 and 0.258, respectively. However, lymph node metastasis exhibited significant worse recurrence-free survival (p=0.033; HR: 2.83, 95% CI: 1.09-7.35), and overall survival (p=0.001; HR: 4.80, 95% CI: 1.82-12.62) compared to those without pelvic lymph node metastasis. In conclusion, it indicates no impact of the MMP-11 SNPs on uterine cervical cancer in Taiwanese women.


Assuntos
Neoplasia Intraepitelial Cervical/genética , Predisposição Genética para Doença , Metaloproteinase 11 da Matriz/genética , Recidiva Local de Neoplasia/genética , Neoplasias do Colo do Útero/genética , Adulto , Idoso , Grupo com Ancestrais do Continente Asiático/genética , Neoplasia Intraepitelial Cervical/patologia , Colo do Útero/patologia , Intervalo Livre de Doença , Feminino , Genótipo , Humanos , Estimativa de Kaplan-Meier , Metástase Linfática/genética , Metástase Linfática/patologia , Pessoa de Meia-Idade , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Polimorfismo de Nucleotídeo Único , Estudos Retrospectivos , Taiwan/epidemiologia , Neoplasias do Colo do Útero/mortalidade , Neoplasias do Colo do Útero/patologia
18.
Medicine (Baltimore) ; 98(30): e16534, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31348270

RESUMO

BACKGROUND: High-grade prostate cancer (PCa) has a poor prognosis, and up to 15% of patients worldwide experience lymph node invasion (LNI). To further improve the prediction lymph node invasion in prostate cancer, we adopted risk scores of the genes expression based on the nomogram in guidelines. METHODS: We analyzed clinical data from 320 PCa patients from the Cancer Genome Atlas database. Weighted gene coexpression network analysis was used to identify the genes that were significantly associated with LNI in PCa (n = 390). Analyses using the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes databases were performed to identify the activated signaling pathways. Univariate and multivariate logistic regression analyses were performed to identify the independent risk factors for the presence of LNI. RESULTS: We found that patients with actual LNI and predicted LNI had the worst survival outcomes. The 7 most significant genes (CTNNAL1, ENSA, MAP6D1, MBD4, PRCC, SF3B2, TREML1) were selected for further analysis. Pathways in the cell cycle, DNA replication, oocyte meiosis, and 9 other pathways were dramatically activated during LNI in PCa. Multivariate analyses identified that the risk score (odds ratio [OR] = 1.05 for 1% increase, 95% confidence interval [CI]: 1.04-1.07, P < .001), serum PSA level, clinical stage, primary biopsy Gleason grade (OR = 2.52 for a grade increase, 95% CI: 1.27-5.22, P = .096), and secondary biopsy Gleason grade were independent predictors of LNI. A nomogram built using these predictive variables showed good calibration and a net clinical benefit, with an area under the curve (AUC) value of 90.2%. CONCLUSIONS: In clinical practice, the application of our nomogram might contribute significantly to the selection of patients who are good candidates for surgery with extended pelvic lymph node dissection.


Assuntos
Biomarcadores Tumorais/genética , Metástase Linfática/genética , Nomogramas , Neoplasias da Próstata/genética , Idoso , Área Sob a Curva , Proteínas de Ciclo Celular/metabolismo , Bases de Dados Genéticas , Endodesoxirribonucleases/metabolismo , Humanos , Peptídeos e Proteínas de Sinalização Intercelular , Modelos Logísticos , Linfonodos/patologia , Masculino , Proteínas Associadas aos Microtúbulos/metabolismo , Pessoa de Meia-Idade , Análise Multivariada , Gradação de Tumores , Proteínas de Neoplasias/metabolismo , Razão de Chances , Peptídeos/metabolismo , Valor Preditivo dos Testes , Neoplasias da Próstata/patologia , Fatores de Processamento de RNA/metabolismo , Receptores Imunológicos/metabolismo , Reprodutibilidade dos Testes , Fatores de Risco , alfa Catenina/metabolismo
19.
Artif Cells Nanomed Biotechnol ; 47(1): 2516-2520, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31213091

RESUMO

It has been found in several studies and research that the long non-coding RNA (Inc RNA) NEAT1 plays an important role in the development and succession in various malignant tumour. The development and metastasis of tumour mainly happen through lymph node. The purpose of this research is to explore the value of lymph node metastasis (LNM) in cancer. We have collected all the concerned studies about NEAT1 and researched the relationship between NEAT1 and lymph node metastasis. We have searched the studies by seeking database PubMed, Web of Science, and China National Knowledge Infrastructure (up to 10 January 2019), as well as a total of 821 patients from eight studies topics and made accordingly meta-analysis. By analyzing the data, we have found that the result is the high expression of NEAT1 associate with the metastasis of lymph node in different malignant tumours. The high level of NEAT1 expression can predict the metastasis of lymph node (OR = 3.36, 95% CI = 1.66-6.77, p = .000) and it is a molecular marker of positive lymph node for treatment.


Assuntos
Metástase Linfática/genética , RNA Longo não Codificante/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Prognóstico
20.
Future Oncol ; 15(19): 2277-2286, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31237166

RESUMO

Aim: To explore whether c-reactive protein/albumin (CRP/Alb) ratio is a poor prognostic factor for patients with oral squamous cell carcinoma (OSCC). Patients & methods: Receiver-operating characteristic analysis was performed to evaluate the optimal cut-off value of CRP/Alb ratio in 240 patients with OSCC. The Kaplan-Meier method was used to plot the overall survival and disease-free survival curves. Cox proportional hazards model was used to implement univariate and multivariate analyses. Results: Preoperative high CRP/Alb ratio was associated with age, advanced stage, lymphatic metastasis, platelet-to-lymphocyte ratio and neutrophil-to-lymphocyte ratio (all p < 0.05). Elevated CRP/Alb ratio independently predicts worse overall survival and disease-free survival of patients with OSCC. Conclusion: Preoperative high CRP/Alb ratio was a poor independent prognostic marker of OSCC.


Assuntos
Proteína C-Reativa/genética , Carcinoma de Células Escamosas/sangue , Neoplasias Bucais/sangue , Albumina Sérica/genética , Adulto , Idoso , Biomarcadores Tumorais/sangue , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Metástase Linfática/genética , Metástase Linfática/patologia , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/genética , Neoplasias Bucais/patologia , Prognóstico
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