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1.
J Cancer Res Clin Oncol ; 146(1): 105-115, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31781865

RESUMO

PURPOSE: We aimed to identify biomarkers of response to preoperative CRT in patients with LARC using comprehensive miRNA analysis. METHODS: This study included 65 rectal cancer specimens and 89 serum samples from patients diagnosed with LARC and treated with preoperative. All specimens were collected before CRT for evaluation of biologic differences between the good and poor CRT response groups (ypStage 0/I versus II/III/IV). For specific miRNA discovery, 800 miRNAs in 20 rectal cancer specimens were analyzed with a NanoString assay. For validation, a total of 65 tissue and 89 serum samples were tested with reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: In the discovery set, 16 target miRNAs were detected. In the validation set, higher expression of three miRNAs (miR-199a/b-3p, miR-199a-5p, and miR-199b-5p) was significantly associated with better response to CRT. In the univariate survival analysis, upregulation of these three miRNAs was associated with superior relapse-free survival (RFS) and overall survival (OS). Meanwhile, only a higher level of tissue miR-199a-5p was associated with superior RFS [hazard ratio (HR), 0.0.91; 95% confidence interval (CI) 0.035-0.580; p = 0.002] and OS (HR, 0.272; 95% CI 0.023-0.658; p < 0.001) in the multivariate survival analysis. Also, a higher level of exosomal miR-199b-5p correlated with better response to CRT (p = 0.0397). CONCLUSION: High expression of tissue miR-199a/b-3p, miR-199a-5p, and miR-199b-5p was significantly associated with response to CRT, and a high level of tissue miR-199a-5p was associated with superior survival outcomes. Also, upregulated exosomal miR-199b-5p correlated with CRT response, reflecting its promise as a circulating biomarker of CRT response in patients with LARC.


Assuntos
MicroRNAs/biossíntese , Neoplasias Retais/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/biossíntese , Biomarcadores Tumorais/genética , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Neoplasias Retais/metabolismo , Neoplasias Retais/mortalidade , Neoplasias Retais/patologia , Taxa de Sobrevida
2.
J Cancer Res Clin Oncol ; 146(1): 75-86, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31754833

RESUMO

PURPOSE: The enzymes gamma-glutamyl hydrolase (GGH) and folylpolyglutamate synthetase (FPGS) regulate intracellular folate concentrations needed for cell proliferation, DNA synthesis, and repair. High GGH expression affects 5-FU thymidylate synthase (TS) inhibition and is a risk factor for various malignancies. Here, the clinical significance of GGH and FPGS expression was investigated in Stage II/III gastric cancer patients undergoing postoperative adjuvant chemotherapy with S-1. METHODS: Surgical specimens of cancer tissue and adjacent normal mucosa, obtained from 253 patients with previously untreated gastric cancer, were examined. GGH and FPGS mRNA expression was measured by qPCR to evaluate their clinicopathological significance in gastric cancer patients after curative resection. RESULTS: While FPGS expression showed no significant differences between the cancerous and normal samples, GGH expression was higher in cancer tissue than in adjacent normal mucosa. High GGH expression was correlated with age, histological type, and vascular invasion. Overall survival (OS) of patients with high GGH mRNA expression was significantly poorer than of patients with low GGH expression. Multivariate analysis showed that high GGH expression was an independent prognostic factor of OS (HR: 2.58, 95% CI 1.29-5.16). Patients who received S-1 adjuvant treatment showed a significantly poor OS between high GGH/low FPGS and low GGH/high FPGS. Patients without adjuvant treatment showed no significant difference. CONCLUSION: GGH expression was significantly higher in gastric cancer tissue than in adjacent normal mucosa. High GGH and low FPGS expression is a useful independent predictor of poor outcomes in stage II/III gastric cancer patients undergoing postoperative adjuvant chemotherapy with S-1.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/biossíntese , Peptídeo Sintases/biossíntese , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/enzimologia , gama-Glutamil Hidrolase/biossíntese , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Quimioterapia Adjuvante , Combinação de Medicamentos , Feminino , Mucosa Gástrica/enzimologia , Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Ácido Oxônico/administração & dosagem , Peptídeo Sintases/genética , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia , Tegafur/administração & dosagem , gama-Glutamil Hidrolase/genética
3.
J Surg Oncol ; 121(3): 547-560, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31867736

RESUMO

BACKGROUND: Na+ /H+ exchanger regulatory factor 1 (NHERF1) has been implicated in the tumorigenesis of several cancer types and is a potential therapeutic target. The current study evaluated the relationship between NHERF1 expression and clinical outcome in colorectal cancer (CRC). METHODS: NHERF1 expression was evaluated by immunohistochemistry in 167 patients with CRC primary tumors, 37 patients with no disease, and 27 patients with metastatic CRC (mCRC); and in the orthotopically implanted tumors in mice. NHERF1 expression was manipulated in CRC cells using inducible short hairpin RNAs to determine its biological functions. RESULTS: High expression of NHERF1 correlated with CRC progression and metastasis, as well as significantly worse overall survival, recurrence-free survival, and disease-specific survival. Orthotopic implantation studies demonstrated increased NHERF1 expression in liver metastases. Treatment of CRC xenografts with insulin-like growth factor 1 receptor (IGF1R) inhibitors downregulated NHERF1 expression, indicating NHERF1 is downstream of IGF1R signaling. Knockdown of NHERF1 increased apoptosis and reduced X-linked inhibitor of apoptosis protein (XIAP) and survivin expression, indicating NHERF1 is critical for CRC cell survival. CONCLUSION: NHERF1 expression levels correlated with worse prognosis in patients with CRC and plays a critical role in CRC cell survival. Together, our findings establish NHERF1 as a novel potential marker for increased risk of CRC-specific mortality and identify NHERF1 as an attractive therapeutic target for mCRC treatment.


Assuntos
Neoplasias Colorretais/metabolismo , Fosfoproteínas/biossíntese , Trocadores de Sódio-Hidrogênio/biossíntese , Idoso , Animais , Biomarcadores Tumorais/biossíntese , Linhagem Celular Tumoral , Neoplasias Colorretais/patologia , Células HCT116 , Xenoenxertos , Humanos , Masculino , Camundongos , Camundongos Nus , Pessoa de Meia-Idade , Taxa de Sobrevida
4.
Tumour Biol ; 41(9): 1010428319878536, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31552812

RESUMO

Histone H2AX undergoes phosphorylation as an answer to DNA double-strand breaks, which in turn are part of the oncogenic procedure. The detection of gamma-H2AX can potentially serve as a biomarker for transformation of normal tissue to premalignant and consequently to malignant tissues. The aim of this study was to evaluate the clinical significance of gamma-H2AX expression in breast cancer. Gamma-H2AX expression in tissues from 110 breast cancer patients was analyzed by immunohistochemistry and correlated with clinicopathological variables. Greater tumor size, higher grade, and the number of affected lymph nodes are significantly associated with greater values of gamma-H2AX. In addition, gamma-H2AX differs significantly among patients' International Federation of Gynecology and Obstetrics stage. Higher values of estrogen receptor and progesterone receptor are significantly associated with lower gamma-H2AX values. In conclusion, a positive association between gamma-H2AX expression and infaust histopathological parameters was observed.


Assuntos
Biomarcadores Tumorais/biossíntese , Neoplasias da Mama Masculina/metabolismo , Neoplasias da Mama/metabolismo , Histonas/biossíntese , Idoso , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/cirurgia , Neoplasias da Mama Masculina/diagnóstico , Neoplasias da Mama Masculina/cirurgia , Feminino , Humanos , Imuno-Histoquímica , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Fosforilação , Receptores Estrogênicos , Receptores de Progesterona
5.
Gene ; 721: 144097, 2019 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-31493507

RESUMO

BACKGROUND: Polo-like kinase 1 (PLK1) is a potential prognostic marker in colorectal cancer (CRC). Nevertheless, the clinicopathological and prognostic roles of PLK1 in CRC are still undefined. Therefore, we performed a meta-analysis to investigate the clinicopathological and prognostic relevance of PLK1 expression in CRC patients. METHODS: Studies published between 2003 and 2016 were selected for the meta-analysis based on an electronic literature search (PubMed, EMBASE and Chinese databases). Studies that investigated the clinicopathological and prognostic impacts of PLK1 expression in CRC patients were included for this analysis. RESULTS: Eleven studies that enrolled 1147 CRC patients were included in our meta-analysis. The effect of PLK1 level on overall survival (OS) was reported in five studies, which included 702 patients. Ten studies investigated the clinicopathological role of PLK1 expression in CRC patients. Consequently, PLK1 overexpression was associated with poorer OS in CRC patients. Furthermore, the results revealed that higher PLK1 levels were also observed in CRC tissues compared with that of normal colorectal tissues. In addition, this meta-analysis also revealed positive correlations between PLK1 upregulation and lymph node metastasis or invasion. PLK1 overexpression was significantly correlated with advanced TNM stages and higher Dukes stages. CONCLUSION: This meta-analysis strongly supports the hypothesis that PLK1 might serve as an important factor in evaluating the biological behavior and prognosis of CRC.


Assuntos
Biomarcadores Tumorais/biossíntese , Proteínas de Ciclo Celular/biossíntese , Neoplasias Colorretais , Regulação Enzimológica da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Proteínas Serina-Treonina Quinases/biossíntese , Proteínas Proto-Oncogênicas/biossíntese , Biomarcadores Tumorais/genética , Proteínas de Ciclo Celular/genética , Neoplasias Colorretais/enzimologia , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Intervalo Livre de Doença , Humanos , Metástase Linfática , Estadiamento de Neoplasias , Proteínas Serina-Treonina Quinases/genética , Proteínas Proto-Oncogênicas/genética , Taxa de Sobrevida
6.
BMC Urol ; 19(1): 69, 2019 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-31340801

RESUMO

BACKGROUND: The expression level of ribonucleotide reductase subunit M1 (RRM1) is closely related to the effect of gemcitabine-based therapy in advanced bladder cancer. However, the value of RRM1 expression in predicting progression-free survival in non-muscle-invasive bladder cancer (NMIBC) patients treated with intravesical gemcitabine chemotherapy has not been elucidated. METHODS: This study randomly assigned 162 patients to either the RRM1-known group or the unknown group. We collected cancer tissues from 81 patients to evaluate the mRNA expression of RRM1 by using liquid chip technology. All patients were diagnosed and then treated with intravesical gemcitabine monotherapy immediately after transurethral resection of the bladder tumour (TURBT). RESULTS: RRM1 expression was high in 21% (17/81) of patients. The RRM1 mRNA level was not correlated with sex, age, weight, performance status, or CUA/EAU risk (p > 0.05). Progression-free survival (PFS) was significantly longer for patients with low RRM1 expression than for patients with high and unknown RRM1 expression (p = 0.009). Additionally, the 1- and 2-year relapse rates also differed according to RRM1 expression level. The 1-year relapse rates for RRM1-low, RRM1-high and RRM1-unknown patients were 0, 17.7 and 6.2% (p = 0.009), while the 2-year relapse rates for these groups were 3.1, 29.4, and 11.1% (p = 0.005), respectively. CONCLUSIONS: This preliminary study showed that low RRM1 expression was associated with longer progression-free survival and lower 1-year/2-year relapse rates in NMIBC patients treated with intravesical gemcitabine monotherapy, despite the need for further verification with large sample sizes and considering more mixed factors and biases.


Assuntos
Antimetabólitos Antineoplásicos/administração & dosagem , Biomarcadores Tumorais/biossíntese , Desoxicitidina/análogos & derivados , Ribonucleosídeo Difosfato Redutase/biossíntese , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/metabolismo , Administração Intravesical , Adulto , Idoso , Idoso de 80 Anos ou mais , Desoxicitidina/administração & dosagem , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/diagnóstico , Valor Preditivo dos Testes , Distribuição Aleatória , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento , Neoplasias da Bexiga Urinária/diagnóstico
8.
Medicine (Baltimore) ; 98(27): e16237, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31277140

RESUMO

Aberrant expression of SRY-box 8 (SOX8) is closely correlated with the development and progression of many types of cancers in human. Limited studies report the relationship between SOX8 expression and overall survival in colorectal cancer (CRC). This study aimed to collect the pathological tissues and clinical data in order to analyze the relationship between SOX8 expression and clinicopathological parameters and prognosis of CRC patients. Tissue microarrays were constructed from 424 primary CRC patients with clinicopathological information and follow-up data. Immunohistochemistry (IHC) was performed on tissue microarrays to explore the relationship between SOX8 expression and clinicopathological information and patient's prognosis. The expression of SOX8 was higher in CRC tissues than that in non-tumor adjacent tissues (NATs, P <.001). High expression of SOX8 was associated with tumor stage (P = .04) and shorter overall survival (OS) after operation of patients (P = .004). Subsequently, univariate COX analysis identified that high expression of SOX8 (P = .004), differentiation (P = .006), distant metastasis (P <.001), tumor stage (P = .003), and higher rate of lymph node metastasis (P <.001), all significantly predicted decrease in OS. Multivariate analysis demonstrated that distant metastasis (P <.001), high SOX8 expression, (P = .013) and lymph node metastasis (P <.001) were independent poor prognostic factors in CRC patients. This study showed that SOX8 is over-expressed in patients with high T stage, which affects the outcome of prognosis in CRC patients. High expression of SOX8 usually has a poor independent prognostic factor for CRC.


Assuntos
Neoplasias Colorretais/genética , DNA de Neoplasias/genética , Regulação Neoplásica da Expressão Gênica , Estadiamento de Neoplasias , Fatores de Transcrição SOXE/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/biossíntese , Biomarcadores Tumorais/genética , China/epidemiologia , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/mortalidade , Progressão da Doença , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Transcrição SOXE/biossíntese , Taxa de Sobrevida/tendências , Análise Serial de Tecidos
9.
Medicine (Baltimore) ; 98(27): e16277, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31277155

RESUMO

Kaposi sarcoma (KS) is an endothelial tumor etiologically related to Kaposi sarcoma herpesvirus (KSHV) infection. The aim of our study was to screen out candidate genes of KSHV infected endothelial cells and to elucidate the underlying molecular mechanisms by bioinformatics methods. Microarray datasets GSE16354 and GSE22522 were downloaded from Gene Expression Omnibus (GEO) database. the differentially expressed genes (DEGs) between endothelial cells and KSHV infected endothelial cells were identified. And then, functional enrichment analyses of gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis were performed. After that, Search Tool for the Retrieval of Interacting Genes (STRING) was used to investigate the potential protein-protein interaction (PPI) network between DEGs, Cytoscape software was used to visualize the interaction network of DEGs and to screen out the hub genes. A total of 113 DEGs and 11 hub genes were identified from the 2 datasets. GO enrichment analysis revealed that most of the DEGs were enrichen in regulation of cell proliferation, extracellular region part and sequence-specific DNA binding; KEGG pathway enrichments analysis displayed that DEGs were mostly enrichen in cell cycle, Jak-STAT signaling pathway, pathways in cancer, and Insulin signaling pathway. In conclusion, the present study identified a host of DEGs and hub genes in KSHV infected endothelial cells which may serve as potential key biomarkers and therapeutic targets, helping us to have a better understanding of the molecular mechanism of KS.


Assuntos
Biomarcadores Tumorais/genética , Biologia Computacional/métodos , Células Endoteliais/metabolismo , Regulação Neoplásica da Expressão Gênica , Herpesvirus Humano 8 , Mapas de Interação de Proteínas/genética , Sarcoma de Kaposi/genética , Biomarcadores Tumorais/biossíntese , DNA de Neoplasias/genética , Células Endoteliais/patologia , Células Endoteliais/virologia , Perfilação da Expressão Gênica/métodos , Ontologia Genética , Humanos , Mapeamento de Interação de Proteínas/métodos , Sarcoma de Kaposi/metabolismo , Sarcoma de Kaposi/virologia
10.
Urologiia ; (2): 40-49, 2019 Jun.
Artigo em Russo | MEDLINE | ID: mdl-31162900

RESUMO

The fundamental question about the origin of cancer stem cells of urothelial carcinomas with luminal remains open. So far, no convincing evidence has been found to determine whether these events occur in a single cell, presumably basal, or are realized in different precursor cells of the urothelium. The potential of a number of potential stem markers as cancer stem cells in urothelial carcinomas and their prognostic significance are currently being investigated. AIM: Our aim was to carry out a comparative analysis of the expression of stem markers in the molecular subtypes of urothelial carcinomas, including ALDH1A1, CXCR4, CD24, CD82, CD105, CD133, NANOG, OCT4 and SOX-2. In addition, the relationship between the pattern of expression and the pathological features of the tumor was determined. PATIENTS AND METHODS: Surgical specimens from 196 patients with a diagnosis of urothelial carcinoma of the renal pelvis and bladder were studied. Immunohistochemical study was performed on paraffin sections using the standard protocol. Antibodies against ALDH1A1, CD82, CD133, CXCR4, NANOG, OCT4, SOX2 ("Abcam"), CD24, CD105 ("Invitrogen"), CD31, CD34 ("Novocastra") were used. RESULTS: The stem cell markers used in the study were expressed in all molecular subtypes of urothelial carcinoma and there were no differences in frequency and intensity of expression between different phenotypes. However, the frequency and intensity of expression of the markers correlated with the tumor stage and the grade of cellular anaplasia. CONCLUSION: Our results confirm that cancer stem cells with basal phenotype are not an exclusive subpopulation in urothelial tumors. Other progenitor cells with the immunophenotype of intermediate and/or umbrella cells can serve as cancer stem cells. These features of the expression in cancer stem cell markers will allow to develop new approaches to the treatment of urothelial carcinomas.


Assuntos
Biomarcadores Tumorais/biossíntese , Carcinoma de Células de Transição/metabolismo , Células-Tronco Neoplásicas/metabolismo , Neoplasias Urológicas/metabolismo , Urotélio/metabolismo , Carcinoma de Células de Transição/patologia , Humanos , Imuno-Histoquímica , Células-Tronco Neoplásicas/patologia , Prognóstico , Neoplasias Urológicas/patologia , Urotélio/patologia
11.
Cancer Treat Rev ; 77: 11-19, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31174180

RESUMO

INTRODUCTION: Identification of membrane proteins expressed exclusively on tumor cells is a goal for cancer drug development. The receptor tyrosine kinase-like orphan receptor type 1 and 2 (ROR1/2), are type-I transmembrane proteins expressed in cancer but not in adult normal tissue. Here, we explore the prognostic role ROR1/2 expression on patient outcome. METHODS: A systematic search of electronic databases identified publications exploring the effect of ROR1/2 on overall survival (OS). Hazard ratios (HR) from collected data were pooled in a meta-analysis using generic inverse-variance and random effects modeling. Subgroup analyses were conducted based on disease site or tumor type. RESULTS: Twenty five studies met the inclusion criteria. ROR1 was associated with worse overall survival (HR 2.13, 95% confidence interval (CI) 1.62-2.80; P < 0.001) with subgroup analysis showing the strongest association between ROR1 and OS was in lung cancer. There was no significant difference between solid tumors and hematological malignancies (HR 2.15, 95% CI 1.52-3.06 vs. HR 2.02, 95% CI 1.46-2.84; subgroup difference P = 0.80). ROR2 was also associated with worse OS (HR 1.84, 95% CI 1.43-2.38; P < 0.001). There was no significant difference between disease sites although the highest association seen was in head and neck cancers (HR 3.19, 95% CI 1.13-8.97) and the lowest in gynecological cancers (HR 1.19, 95% CI 0.71-2.00; subgroup difference P = 0.10). CONCLUSIONS: ROR1 and ROR2 expression is associated with adverse outcome in several tumors. ROR1/2 warrants study as a target for developmental therapeutics.


Assuntos
Neoplasias/metabolismo , Neoplasias/mortalidade , Receptores Órfãos Semelhantes a Receptor Tirosina Quinase/biossíntese , Biomarcadores Tumorais/biossíntese , Humanos , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida
12.
Medicine (Baltimore) ; 98(24): e15982, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31192939

RESUMO

BACKGROUND: FEZ family zinc finger 1 antisense RNA 1 (FEZF1-AS1), as a novel lncRNA, was reported to be up-regulated in various cancers and involved in tumor progression. This study systematically assessed the prognostic value of FEZF1-AS1 in solid tumors. METHODS: Web of Science, PubMed, EMBASE, Chinese National Knowledge Infrastructure, and Wanfang databases were searched for eligible studies that evaluated the prognostic role of FEZF1-AS1 expression in cancer patients. Pooled hazard ratios (HRs) and combined odds ratios (ORs) with their 95% confidence intervals (CIs) were calculated. The meta-analysis was conducted using Stata/SE 14.1. RESULTS: Fifteen original studies involving 1378 patients were enrolled. Pooled results showed that increased expression of FEZF1-AS1 significantly correlated with shorter overall survival (OS) in cancer patients (HR 2.04, 95% CI 1.60-2.47), and also shorter disease-free survival (DFS) (HR 2.08, 95% CI 1.27-2.89). Additionally, the combined ORs indicated that increased FEZF1-AS1 expression was significantly associated with lymph node metastasis (OR 3.35, 95% CI 1.98-5.67), distant metastasis (OR 3.10, 95% CI 1.86-5.15), poor tumor differentiation (OR 2.90, 95% CI 1.45-5.80), high depth of tumor invasion (OR 2.72, 95% CI 1.36-5.43), and advanced clinical stage (OR 2.76, 95% CI 1.75-4.35). Expression analysis using the Gene Expression Profiling Interactive Analysis database indicated that the expression of FEZF1-AS1 was higher in tumor tissues than that in the corresponding normal tissues. The results of survival analysis revealed that increased FEZF1-AS1 expression was correlated with poor OS and DFS in cancer patients. CONCLUSIONS: LncRNA FEZF1-AS1 may serve as a valuable prognostic biomarker for clinical outcomes in various solid tumors.


Assuntos
Neoplasias/genética , RNA Antissenso/genética , RNA Longo não Codificante/genética , Fatores de Transcrição/genética , Biomarcadores Tumorais/biossíntese , Biomarcadores Tumorais/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Metástase Linfática , Neoplasias/metabolismo , Razão de Chances , Prognóstico , RNA Antissenso/biossíntese , Proteínas Repressoras , Análise de Sobrevida , Regulação para Cima
13.
J Clin Pathol ; 72(8): 513-519, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31154423

RESUMO

The importance of circular RNAs (circRNAs) in pathological processes like cancer is evident. Among the circRNAs, recent studies have brought circPVT1 under focus as the most potent oncogenic non-coding RNA. Recent studies on various aspects of circPVT1, including its biogenesis, molecular alteration and its probable role in oncogenesis, have been conducted for research and clinical interest. In this review, a first attempt has been made to summarise the available data on circPVT1 from PubMed and other relevant databases with special emphasis on its role in development, progression and prognosis of various malignant conditions. CircPVT1 is derived from the same genetic locus encoding for long non-coding RNA lncPVT1; however, existing literature suggested circPVT1 and lncPVT1 are transcripted independently by different promoters. The interaction between circRNA and microRNA has been highlighted in majority of the few malignancies in which circPVT1 was studied. Besides its importance in diagnostic and prognostic procedures, circPVT1 seemed to have huge therapeutic potential as evident from differential drug response of cancer cell line as well as primary tumors depending on expression level of the candidate. circPVT1 in cancer therapeutics might be promising as a biomarker to make the existing treatment protocol more effective and also as potential target for designing novel therapeutic intervention.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias/genética , RNA/genética , Animais , Biomarcadores Tumorais/biossíntese , Transformação Celular Neoplásica/genética , Transformação Celular Neoplásica/metabolismo , Transformação Celular Neoplásica/patologia , Regulação Neoplásica da Expressão Gênica , Humanos , Técnicas de Diagnóstico Molecular , Neoplasias/metabolismo , Neoplasias/patologia , Neoplasias/terapia , Valor Preditivo dos Testes , Prognóstico , RNA/biossíntese , RNA Longo não Codificante/biossíntese , RNA Longo não Codificante/metabolismo
14.
PLoS One ; 14(5): e0216793, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31150395

RESUMO

Renal carcinoma is the 20th most common cancer worldwide. Clear cell renal cell carcinoma is the most frequent type of renal cancer. Even in patients diagnosed at an early stage, characteristics of disease progression remain heterogeneous. Up-to-date molecular classifications stratify the ccRCC samples into two clusters. We analyzed gene expression in 23 T1 or T3 ccRCC samples. Unsupervised clustering divided this group into three clusters, two of them contained pure T1 or T3 samples while one contained a mixed group. We defined a group of 36 genes that discriminate the mixed cluster. This gene set could be associated with tumor classification into a higher stage and it contained significant number of genes coding for molecular transporters, channel and transmembrane proteins. External data from TCGA used to test our findings confirmed that the expression levels of those 36 genes varied significantly between T1 and T3 tumors. In conclusion, we found a clustering pattern of gene expression, informative for heterogeneity among T1 and T3 tumors of clear cell renal cell carcinoma.


Assuntos
Biomarcadores Tumorais/biossíntese , Carcinoma de Células Renais/metabolismo , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Neoplasias Renais/metabolismo , Proteínas de Membrana/biossíntese , Proteínas de Neoplasias/biossíntese , Biomarcadores Tumorais/genética , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/patologia , Feminino , Humanos , Neoplasias Renais/genética , Neoplasias Renais/patologia , Masculino , Proteínas de Membrana/genética , Pessoa de Meia-Idade , Proteínas de Neoplasias/genética
15.
Biomed Res Int ; 2019: 2582416, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31183364

RESUMO

Introduction: Glioblastoma (GBM) is the most frequent and malignant type of primary brain tumors in adults. The valuable prognostic biomarkers and therapeutic targets for GBM remain to be elucidated. The association of adipokines with cancer has been well documented. The C1q/TNF-related protein 1 (CTRP1), a novel adipokine, belongs to the CTRP family. Methods: In the present study, the expression and potential roles of CTRP1 in GBM were explored based on in silico evaluation, including GEPIA, the Pathology Atlas of the Human Protein Atlas, cBioPortal, TIMER, and SurvExpress. The CCK8, transwell, and wound healing assays were used to detect cell proliferation and migration. Results: It was found that mRNA expression levels of CTRP1 were significantly upregulated in GBM tissues compared with those in nontumor tissues according to the analysis on public dataset and immunohistochemical results of GBM tissues (P<0.05). CTRP1 was mainly localized in the cytoplasm and cell membrane of GBM cells. The genetic alterations of CTRP1 occurred at a low rate in GBM (2 of 591 sequenced cases/patients, 0.33%). The mRNA expression levels of CTRP1 were positively associated with the tumor-infiltrating macrophages and CCL2 in GBM (P<0.05, respectively). The higher mRNA expression levels of CTRP1 were significantly correlated with higher risk and shorter overall survival time in GBM (P<0.05). CTRP1 knockdown significantly inhibited the proliferation and migration in human GBM cells, suggesting the inhibition of CTRP1 on human GMB progression. Moreover, CTRP1 knockdown inhibited CCL2 expression, and CCL2 overexpression reversed the inhibition of cell proliferation and migration induced by CTRP1 knockdown, suggesting that CTRP1 promoted tumor progression by regulating CCL2 expression. Conclusions: These findings suggest that CTRP1 potentially indicates poor prognosis in GBM and promotes the progression of human GBM.


Assuntos
Biomarcadores Tumorais/biossíntese , Neoplasias Encefálicas , Regulação Neoplásica da Expressão Gênica , Glioblastoma , Proteínas Oncogênicas/biossíntese , Proteínas/metabolismo , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/patologia , Linhagem Celular Tumoral , Intervalo Livre de Doença , Feminino , Glioblastoma/metabolismo , Glioblastoma/mortalidade , Glioblastoma/patologia , Humanos , Masculino , Taxa de Sobrevida
16.
Med Sci Monit ; 25: 4278-4284, 2019 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-31177263

RESUMO

BACKGROUND Monocarboxylate transporter 4 (MCT4) is a critical element for glycolytic metabolism and malignant behaviors in many tumor cells. This study aimed to determine the expression level of MCT4 protein and its prognostic value in osteosarcoma. MATERIAL AND METHODS MCT4 expression was detected via immunohistochemical and Western blot analysis for 100 osteosarcoma patients. The correlation between MCT4 expression and clinical factors among the patients was analyzed using the chi-square test. Overall survival of osteosarcoma patients was estimated by Kaplan-Meier analysis. The prognostic value of MCT4 was evaluated using Cox regression analysis with adjustments for clinicopathological variables. RESULTS MCT4 expression was significantly upregulated in osteosarcoma tissues compared with that in adjacent normal ones, detected via both immunohistochemical and Western blot analyses. High MCT4 expression showed a positive association with distant metastasis (P=0.000) and recurrence (P=0.000) of osteosarcoma. Kaplan-Meier analysis indicated that overall survival of osteosarcoma patients was significantly higher in the low MCT4 expression group than in the high expression group (log-rank test, P<0.001). Multivariate analysis indicated that MCT4 expression and clinical stage, which are tightly related to the prognosis of osteosarcoma, might be independent predictors of osteosarcoma prognosis. CONCLUSIONS High MCT4 expression appears to contribute to osteosarcoma progression and the upregulation of MCT4 may predict poor prognosis among osteosarcoma patients.


Assuntos
Neoplasias Ósseas/metabolismo , Transportadores de Ácidos Monocarboxílicos/biossíntese , Proteínas Musculares/biossíntese , Osteossarcoma/metabolismo , Adulto , Biomarcadores Tumorais/biossíntese , Biomarcadores Tumorais/genética , Neoplasias Ósseas/genética , Neoplasias Ósseas/patologia , Intervalo Livre de Doença , Feminino , Perfilação da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Transportadores de Ácidos Monocarboxílicos/genética , Proteínas Musculares/genética , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/metabolismo , Recidiva Local de Neoplasia/patologia , Osteossarcoma/genética , Osteossarcoma/patologia , Prognóstico , Modelos de Riscos Proporcionais , Transcriptoma
17.
Medicine (Baltimore) ; 98(25): e16050, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31232941

RESUMO

BACKGROUND: miR-222 is one of the most consistently overexpressed miRNAs in papillary thyroid carcinoma (PTC). Previous studies demonstrated that miR-222 overexpression conferred high-risk features in PTC patients, suggesting its value in risk-stratification. However, studies in term of miR-222's utility on stratifying PTCs are lacking. METHODS: One hundred patients including 10 with multinodular goiter and 90 with PTC were enrolled. Formalin-fixed paraffin-embedded samples were exploited for miR-222 quantitative reverse transcriptase- polymerase chain reaction (RT-PCR) analysis. Correlations between miR-222 expression and different clinicopathological features, Tumor-node-metastasis (TNM) staging and ATA risk level were analyzed. RESULTS: miR-222 expression of the PTC group was significantly higher than that of the goiter group (P < .001). Furthermore, miR-222 expression was significantly higher in PTCs with advanced features like larger tumor, capsular invasion, vascular invasion and lymph nodes metastasis. The majority of patients (61%) were in stage I group (similar to ATA low-risk) by TNM staging system. As to the ATA system, the majority (73%) were in intermediate-risk group (similar to TNM stage II and III roughly). Contrary to previous report, here we found that miR-222 expression was correlated with the ATA risk level (P < .001), but not with the TNM staging (P = .122). CONCLUSION: In the present study, we demonstrated that miR-222 overexpression was correlated with advanced features like capsular invasion, vascular invasion, larger tumor size and lymph node metastasis in PTCs. Most importantly, miR-222 expression was correlated with ATA risk levels, suggesting its potential value in PTC risk-stratification.


Assuntos
MicroRNAs/análise , Medição de Risco/métodos , Câncer Papilífero da Tireoide/classificação , Adolescente , Adulto , Idoso , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/biossíntese , Biomarcadores Tumorais/sangue , China , Feminino , Humanos , Masculino , Oncologia/organização & administração , MicroRNAs/biossíntese , MicroRNAs/sangue , Pessoa de Meia-Idade , Prognóstico , Câncer Papilífero da Tireoide/sangue
18.
Mol Cell Biochem ; 459(1-2): 35-47, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31073886

RESUMO

Recent study implicates that gastric cancer stem cells (CSCs) are capable of generating multiple types of cells to promote tumor growth and heterogeneity important for the development of gastric cancer. However, knowledge is limited regarding the expression and characteristics of marker-positive gastric CSCs. Therefore, gastric CSCs from a series of human gastric cancer cell lines (SNU-5, SNU-16, BGC-823, PAMC-82, MKN-45, and NCI-N87) using four putative CSC surface markers (CD44, CD90, CD133, and epithelial-cell adhesion molecule) were investigated the underlying mechanisms regulating such subpopulations. Only SNU-5 and SNU-16 exhibited independent co-expression of CD44+ and CD90+, which exhibited spheroid-colony formation in vitro and tumor formation in immunodeficient mice. Functional studies revealed that CD44+ cells were more invasive compared with CD90+ cells, whereas CD90+ cells exhibited higher levels of proliferation than CD44+ cells. Furthermore, serial xenotransplantation in mice of CD44+/CD90+ cells derived from SNU-5 and SNU-16 revealed rapid growth of CD90+ cells in subcutaneous lesions and a high metastatic capacity of CD44+ cells in the lung. Mechanistic analyses revealed that CD44+ cells underwent epithelial-to-mesenchymal transition (EMT) following acquisition of mesenchymal features, whereas CD90+ cells enhanced the activation of retinoblastoma phosphorylation at Ser780 and oncogenic cell cycle regulators. The expression of CD44 and CD90 in gastric cancer tissues was associated with distant metastasis and the differentiation state of tumors. These results demonstrated that CD44 and CD90 are specific biomarkers capable of identifying and isolating metastatic and tumorigenic CSCs through their ability to regulate EMT and the cell cycle in gastric cancer cell lines.


Assuntos
Biomarcadores Tumorais/biossíntese , Regulação Neoplásica da Expressão Gênica , Receptores de Hialuronatos/biossíntese , Proteínas de Neoplasias/biossíntese , Células-Tronco Neoplásicas/metabolismo , Neoplasias Gástricas/metabolismo , Antígenos Thy-1/biossíntese , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Biomarcadores Tumorais/genética , Ciclo Celular , Linhagem Celular Tumoral , Feminino , Humanos , Receptores de Hialuronatos/genética , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Pessoa de Meia-Idade , Metástase Neoplásica , Proteínas de Neoplasias/genética , Células-Tronco Neoplásicas/patologia , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Antígenos Thy-1/genética
19.
Biomed Res Int ; 2019: 1275491, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31061820

RESUMO

Background: As a newly discovered lncRNA, bladder cancer-associated transcript 1 (BLACAT1) has been reported to correlate with poor clinical outcomes in several different cancers. This study aimed to evaluate its generalized predictive value for cancer prognosis. Materials and Methods: We thoroughly searched PubMed, Embase, and Web of Science databases for eligible studies published until November 11, 2018, in which the relationship between BLACAT1 expression and cancer prognosis was explored. The analyses were performed using Review Manager Version 5.3 and Stata SE 12.0. The primary endpoints included overall survival (OS), pathological characteristics (TNM stage and tumor grade), lymph node metastasis (LNM), and distant metastasis. Results: Ten studies containing 861 patients with 7 different cancerous diseases were eventually included. The results demonstrated that patients with high lncRNA BLACAT1 expression had a significantly shorter OS (HR: 1.82, 95% CI: 1.44-2.30, p < 0.00001) than patients with low lncRNA BLACAT1 expression. Moreover, elevated BLACAT1 expression was significantly associated with advanced TNM stage (OR: 2.29, 95% CI: 1.15-4.56, p = 0.005), high tumor grade (OR: 1.67, 95% CI: 1.11-2.53, p = 0.01), and lymph node metastasis (OR: 2.53, 95% CI: 1.80-3.57, p < 0.00001). Meanwhile, the expression of BLACAT1 had no significant association with age (p = 0.92), gender (p = 0.55), and smoking (p = 0.62). Conclusion: High expression of lncRNA BLACAT1 may predict a poor prognosis in OS, TNM stage, tumor grade, and LNM. Its predictive roles were not significantly affected by age, gender, or smoking. Therefore, lncRNA BLACAT1 may serve as a promising predictor in cancer prognosis.


Assuntos
Biomarcadores Tumorais/biossíntese , Regulação Neoplásica da Expressão Gênica , Neoplasias/metabolismo , Neoplasias/mortalidade , RNA Longo não Codificante/biossíntese , Intervalo Livre de Doença , Feminino , Humanos , Metástase Linfática , Masculino , Estadiamento de Neoplasias , Neoplasias/patologia , Valor Preditivo dos Testes , RNA Neoplásico , Taxa de Sobrevida
20.
Biomed Res Int ; 2019: 2063823, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31061821

RESUMO

Background: Although several studies have proved the relationship between the prognostic value of miRNA-15a and different types of cancer, the result remains controversial. Thus, a meta-analysis was conducted to clarify the prognostic value of miRNA-15a expression level in human cancers. Methods: We enrolled appropriate literature by searching the databases of PubMed, Embase, and Web of Science. Subsequently, we extracted HRs and their 95% CIs and calculated pooled results of miRNA-15a for overall survival (OS) and disease-free survival (DFS). Besides, subgroup analysis, sensitivity analysis, and publication bias were also revealed in this study. We also further validated this meta-analysis using the Kaplan-Meier plotter database. Result: 10 studies, including 1616 patients, were embraced in our meta-analysis. The result showed the lower expression of miRNA-15a significantly predicted adverse OS (HR=2.17, 95% CI: 1.41-3.34), but there is no significant association between the expressing level and DFS in cancer patient (HR=2.04, 95% CI: 0.60-6.88). Based on Kaplan-Meier plotter database, we found the same results in bladder Carcinoma, head-neck squamous cell carcinoma, liver hepatocellular carcinoma, lung squamous cell carcinoma, pancreatic ductal adenocarcinoma, rectum adenocarcinoma, stomach adenocarcinoma, and uterine corpus endometrial carcinoma, but opposite results were found in cervical squamous cell carcinoma and esophageal carcinoma. Conclusion: Low expressing levels of miRNA-15a indicated poor OS, while miRNA-15a can be used as a prediction biomarker in different cancer types.


Assuntos
Biomarcadores Tumorais/biossíntese , Biologia Computacional , Regulação Neoplásica da Expressão Gênica , Neoplasias/metabolismo , Neoplasias/mortalidade , RNA Neoplásico/biossíntese , Biomarcadores Tumorais/genética , Intervalo Livre de Doença , Humanos , MicroRNAs , Neoplasias/genética , Neoplasias/patologia , Valor Preditivo dos Testes , RNA Neoplásico/genética , Taxa de Sobrevida
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