Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 11.831
Filtrar
1.
Anticancer Res ; 39(10): 5381-5391, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31570433

RESUMO

BACKGROUND/AIM: Long noncoding RNAs (lncRNAs) are noncoding transcripts that are >200 nucleotides in length. However, the biological functions and regulation mechanisms of lncRNAs in gastric carcinogenesis remain unknown. MATERIALS AND METHODS: The expression levels of Linc00472 were analyzed by real-time PCR. The DNA methylation status was assessed using Combined Bisulfite Restriction Analysis (COBRA). The biological role of Linc00472 was assessed in AGS cells with Linc00472 overexpression. RESULTS: Using the next-generation sequencing approach, we identified DNA methylation-associated lncRNAs in gastric cancer cells. Among them, the expression level of Linc00472 significantly decreased in gastric cancer tissues compared to adjacent normal tissues. Furthermore, we observed a more frequent hypermethylation of CpG islands upstream of Linc00472 in gastric cancer tissues. Ectopic Linc00472 expression could significantly inhibit gastric cancer cell growth and migration. CONCLUSION: Epigenetically regulated Linc00472 expression plays a crucial role in modulating gastric cancer cell growth and motility.


Assuntos
Metilação de DNA/genética , RNA Longo não Codificante/genética , Neoplasias Gástricas/genética , Carcinogênese/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Ilhas de CpG/genética , Regulação Neoplásica da Expressão Gênica/genética , Humanos
2.
Anticancer Res ; 39(10): 5715-5720, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31570472

RESUMO

BACKGROUND/AIM: The PRKCI gene encodes Protein kinase C iota. The overexpression of protein kinase C iota is associated with poor outcomes in patients with gastric and other cancers, but the role of the PRKCI gene in gastric cancer is not fully understood. Thus, we evaluated the clinical significance of PRKCI gene expression in gastric cancer. MATERIALS AND METHODS: PRKCI mRNA expression levels in cancerous tissues and adjacent normal mucosa from 398 patients with gastric cancer were measured. Relationships between PRKCI gene expression and clinicopathological characteristics and outcomes were examined. RESULTS: Overall survival was lower in patients with a high expression of PRKCI than in those with low expression (p=0.016). No other relationships were observed. A high PRKCI expression was found to be an independent prognostic factor (p=0.036, HR=1.44, 95%CI=1.02-2.02). CONCLUSION: PRKCI gene expression in cancerous tissue might be a useful prognostic factor in patients with gastric cancer after gastrectomy.


Assuntos
Expressão Gênica/genética , Isoenzimas/genética , Proteína Quinase C/genética , Neoplasias Gástricas/genética , Gastrectomia/métodos , Mucosa Gástrica/patologia , Humanos , Prognóstico , RNA Mensageiro/genética , Neoplasias Gástricas/patologia
3.
Arq Bras Cir Dig ; 32(3): e1449, 2019.
Artigo em Inglês, Português | MEDLINE | ID: mdl-31644669

RESUMO

INTRODUCTION: The matrix metalloproteinase-7 (MMP-7) gene -181A>G polymorphism has been reported to be associated with colorectal cancer (CRC) and gastric cancer (GC) susceptibility, yet the results of these previous results have been inconsistent or controversial. AIM: To elaborate a meta-analysis to assess the association of -181A>G polymorphism of MMP-7 with CRC and GC risk. METHODS: Published literature evaluating the association from PubMed, Web of Science, Google Scholar and other databases were retrieved up to April 25, 2018. Pooled odds ratio (OR) and 95% confidence interval (CI) were calculated using random- or fixed-effects model. RESULTS: A total of 19 case-control studies, which included eleven studies on CRC (2,169 CRC cases and 2,346 controls) and eight studies on GC (1,545 GC cases and 2,366 controls) were identified. There was a significant association between MMP-7 -181A>G polymorphism and GC risk under the homozygote model (GG vs. AA: OR=1.672, 95% CI 1.161-2.409, p=0.006) and the recessive model (GG vs. GA+AA: OR=1.672, 95% CI 1.319-2.554, p=0.001), but not with CRC. By subgroup analysis based on ethnicity, an increased risk of CRC and GC was found only among Asians. CONCLUSIONS: This meta-analysis suggests that MMP-7 -181A>G polymorphisms is associated with GC risk, but not with CRC. However, our results clearly showed that the MMP-7 -181A>G polymorphism significantly increased the risk of CRC only in Asians.


Assuntos
Neoplasias Colorretais/genética , Predisposição Genética para Doença , Metaloproteinase 7 da Matriz/genética , Polimorfismo Genético/genética , Neoplasias Gástricas/genética , Grupo com Ancestrais do Continente Asiático/genética , Predisposição Genética para Doença/etnologia , Humanos , Razão de Chances , Fatores de Risco
4.
J Cancer Res Clin Oncol ; 145(10): 2507-2517, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31485766

RESUMO

BACKGROUND: Autophagy plays an important role in regulating cisplatin (CDDP) resistance in gastric cancer cells. However, the underlying mechanism of methioninase (METase) in the regulation of autophagy and CDDP resistance of gastric cancer cells is still not clear. MATERIALS AND METHODS: Western blot was used to detect the levels of autophagy-related proteins, multidrug-resistant 1 (MDR-1), and FoxM1 protein. LncRNA HULC was detected by qRT-PCR. Cell viability was detected using CCK-8 assay. The interaction between lncRNA HULC and FoxM1 was confirmed by RNA pull-down and RIP assay. RESULTS: Lentiviral vector carrying METase (LV-METase) suppressed autophagy and CDDP resistance of drug-resistant gastric cancer cells. LncRNA HULC was significantly downregulated in drug-resistant gastric cancer cells transfected with LV-METase. Besides, we found that lncRNA HULC interacted with FoxM1. In addition, METase suppressed autophagy to reduce CDDP resistance of drug-resistant gastric cancer cells through regulating HULC/FoxM1, and interfering HULC suppressed autophagy to reduce CDDP resistance of drug-resistant gastric cancer cells through regulating FoxM1. Finally, interfering HULC inhibited tumor growth in vivo. CONCLUSION: METase suppressed autophagy to reduce CDDP resistance of drug-resistant gastric cancer cells through regulating HULC/FoxM1 pathway.


Assuntos
Autofagia/efeitos dos fármacos , Autofagia/genética , Resistencia a Medicamentos Antineoplásicos/genética , Proteína Forkhead Box M1/metabolismo , Proteínas Proto-Oncogênicas c-met/metabolismo , RNA Longo não Codificante/genética , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Animais , Linhagem Celular Tumoral , Sobrevivência Celular , Cisplatino/farmacologia , Modelos Animais de Doenças , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Camundongos , Ligação Proteica , Neoplasias Gástricas/patologia , Ensaios Antitumorais Modelo de Xenoenxerto
5.
Cancer Invest ; 37(9): 417-426, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31483161

RESUMO

To investigate the molecular mechanisms of gastric carcinogenesis after Helicobacter pylori (H. pylori) eradication, expression of miR-124a, miR-34b, and miR-34c was examined in nonneoplastic gastric specimens after successful H. pylori eradication. The magnifying narrow-band imaging (NBI) endoscopic features of gastric mucosa were also examined. The atrophic type, an informative endoscopic feature for histological intestinal metaplasia, showed lower expression of miR-124a. Lower expression of miR-124a correlated with hypermethylation of the miR-124a3 locus. The atrophic type represents gastric microarchitectures associated with irreversibility with H. pylori eradication and downregulation of miR-124a.


Assuntos
Regulação para Baixo , Mucosa Gástrica/diagnóstico por imagem , Infecções por Helicobacter/prevenção & controle , MicroRNAs/genética , Imagem de Banda Estreita/métodos , Neoplasias Gástricas/genética , Idoso , Idoso de 80 Anos ou mais , Metilação de DNA , Erradicação de Doenças , Epigênese Genética , Feminino , Mucosa Gástrica/patologia , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Gástricas/diagnóstico por imagem
6.
J Cancer Res Clin Oncol ; 145(11): 2689-2697, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31541339

RESUMO

PURPOSE: Gastric cancer is the third leading cause of cancer-related death. Recently, innovative diagnostic and prognostic molecular subtypes have been proposed. We revealed that extranodal extension (ENE) of lymph-node metastases independently influences survival. Therefore, the aim of the present study was to evaluate novel molecular subtyping with regard to the growth pattern of lymph-node metastases. METHODS: A total of 189 gastric carcinomas with lymph-node metastases were analyzed. The expression of p53, SOX2, SOX9, and the mismatch-repair gene products MLH1, PMS2, MSH2, and MSH6 were analyzed by immunohistochemistry. To determine the correlation with EBV infection, in situ hybridization for EBV-encoded small RNA (EBER) was applied. RESULTS: ENE was present in 36% of patients. EBV-positive carcinoma was evident in 5.8%, and p53 aberrant (chromosomal instable) tumors in 22.2%, a gastric cancer with deficient mismatch-repair status in 9%, and MSS/p53neg/EBVneg tumors were seen in 63% of patients. There was no significant correlation between the presence or absence of ENE and the molecular subtypes. However, a significant association between molecular subgroups and the Lauren classification, the oncogene SOX2, and tumor grading was detected. CONCLUSION: The present findings suggest that alterations in gastric cancer leading to ENE are not associated with alterations underpinning the molecular subgroups. Nonetheless, molecular subtyping on the basis of IHC and ISH is feasible and might become clinical routine. Thus, further studies are needed to clarify the mechanisms of extranodal extension in gastric cancer.


Assuntos
Adenocarcinoma/classificação , Adenocarcinoma/secundário , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Neoplasias Gástricas/classificação , Neoplasias Gástricas/patologia , Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Prognóstico , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Taxa de Sobrevida , Adulto Jovem
7.
Presse Med ; 48(9): 904-914, 2019 Sep.
Artigo em Francês | MEDLINE | ID: mdl-31561847

RESUMO

About 5% of colorectal cancer (CRC) cases occurred in the context of an underlying hereditary predisposition syndrome. Lynch syndrome is the main causes of hereditary CRC but is also associated with a higher risk of other cancers (such as endometrial cancer and ovarian cancer). It is the consequence of constitutional mutation in a MisMatch Repair (MMR) gene, involved in DNA repair: MLH1, MSH2, MSH6 or PMS2; or of the EPCAM gene (MSH2 promotor). If a mutation predisposing to Lynch Syndrome is identified in an individual, special monitoring should be initiated, adapted to estimated cancer risk. Clinical criteria (Amsterdam II and Bethesda) have been validated to identify the patients who should be referred for genetic counseling in order to initiate constitutional DNA testing. Furthermore, the French National Cancer Institute (INCa) systematically recommend tumoral testing looking for MMR system failure in case of CRC diagnosed under 60, endometrial cancer diagnosed under 50 or whatever the age in patients diagnosed with CRC or endometrial cancer harbouring personal or familal history of Lunch Syndrome cancers. In this review, we will discuss how to detect Lynch syndrome (identification of the index case and family screening) and how to monitor it in 2019.


Assuntos
Neoplasias Colorretais Hereditárias sem Polipose/diagnóstico , Neoplasias Colorretais Hereditárias sem Polipose/terapia , Adenocarcinoma/diagnóstico , Adenocarcinoma/genética , Fatores Etários , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/genética , Neoplasias Colorretais Hereditárias sem Polipose/genética , Reparo de Erro de Pareamento de DNA/genética , Detecção Precoce de Câncer , Neoplasias do Endométrio/diagnóstico , Neoplasias do Endométrio/genética , Feminino , Predisposição Genética para Doença/genética , Humanos , Intestino Grosso , Pessoa de Meia-Idade , Mutação , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/genética , Linhagem , Vigilância da População/métodos , Guias de Prática Clínica como Assunto , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/genética , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/genética , Neoplasias Urológicas/diagnóstico , Neoplasias Urológicas/genética
8.
Anticancer Res ; 39(9): 4711-4720, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31519570

RESUMO

BACKGROUND/AIM: Dynamics of circulating tumor cells (CTCs) after molecular targeting therapy remain unclear. MATERIALS AND METHODS: We examined changes in CTC numbers and morphology early after targeting therapy in EGFR-mutated PC-9 human lung cancer and HER2-gene amplified GLM-1 gastric cancer mouse CTC models using a cytology-based semi-automated CTC detection platform. RESULTS: Erlotinib and T-DM1 inhibited cell growth mainly by induction of apoptosis in vitro. The number of CTCs detected 5-10 days after targeting therapy in mice was significantly increased compared to CTC numbers before therapy. The increased CTCs after therapy consisted of apoptotic CTCs and viable CTCs. This heterogeneous population of CTCs reflects well the cell population of the primary tumor disrupted by therapy. CONCLUSION: CTCs can be mobilized from the primary tumor due to tissue disruption in acute response to targeting therapy, suggesting potential usefulness of CTC monitoring as a predictor of therapeutic response in the clinical settings.


Assuntos
Amplificação de Genes , Mutação , Células Neoplásicas Circulantes/metabolismo , Receptor ErbB-2/genética , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Animais , Antineoplásicos/farmacologia , Biomarcadores , Biomarcadores Tumorais , Linhagem Celular Tumoral , Modelos Animais de Doenças , Receptores ErbB/genética , Cloridrato de Erlotinib/farmacologia , Xenoenxertos , Humanos , Imuno-Histoquímica , Camundongos , Células Neoplásicas Circulantes/patologia , Neoplasias Gástricas/tratamento farmacológico
9.
J Surg Oncol ; 120(5): 831-846, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31373005

RESUMO

Cancers of the esophagus and stomach remain important causes of mortality worldwide, in large part because they are most often diagnosed at advanced stages. Thus, it is imperative that we identify and treat these cancers in earlier stages. Due to significant heterogeneity in incidence and risk factors for these cancers, it has been challenging to develop standardized screening recommendations. This review summarizes the current recommendations for screening populations at high risk of developing esophagogastric cancers.


Assuntos
Detecção Precoce de Câncer/métodos , Neoplasias Esofágicas/diagnóstico , Predisposição Genética para Doença , Neoplasias Gástricas/diagnóstico , Neoplasias Esofágicas/epidemiologia , Neoplasias Esofágicas/genética , Humanos , Prevalência , Fatores de Risco , Neoplasias Gástricas/epidemiologia , Neoplasias Gástricas/genética
10.
Anticancer Res ; 39(8): 4003-4010, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31366481

RESUMO

Epstein-Barr virus (EBV)-associated gastric cancer (GC) (EBVaGC) is classified as one of four GC subtypes by comprehensive molecular characterization. Though the mechanism of tumorigenesis by EBV infection has not yet been fully clarified, EBV infection might contribute to the malignant transformation of GC cells by involving various cellular processes and signaling pathways. EBVaGC has shown the following distinct characteristics in contrast to other subtypes: extreme DNA hypermethylation, recurrent phosphatidylinositol 4,5-biphosphate 3-kinase catalytic subunit alpha isoform (PIK3CA) mutations, overexpression of programmed cell death ligand 1/2 (PD-L1/2), and occasional immune cell signaling activation. Therefore, using these molecular features as guides, targeted agents need to be evaluated in clinical trials for EBVaGC. Accordingly, this review uses the best available evidence to focus on novel therapeutic approaches using the distinct pathologic characteristics of EBVaGC patients.


Assuntos
Carcinogênese/genética , Infecções por Vírus Epstein-Barr/terapia , Neoplasias Gástricas/terapia , Classe I de Fosfatidilinositol 3-Quinases/genética , Metilação de DNA/genética , Infecções por Vírus Epstein-Barr/genética , Infecções por Vírus Epstein-Barr/virologia , Regulação Neoplásica da Expressão Gênica/genética , Herpesvirus Humano 4/genética , Herpesvirus Humano 4/patogenicidade , Humanos , Neoplasias Gástricas/genética , Neoplasias Gástricas/virologia
11.
Anticancer Res ; 39(8): 4019-4022, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31366483

RESUMO

Historically, analysis of intragastric exfoliative cytology (IEC) of gastric cancer (GC) was used with a diagnostic intent only. With the successful advent of endoscopic biopsy, the rate of detection of GC has improved worldwide and, as a consequence, IEC has been progressively abandoned. Today, however, there is a renewed interest in this field of research, as witnessed by several pertinent publications. As discussed in this review, in fact, currently the importance of analyzing IEC in patients with early and advanced GC seems to reside in its clinicopathological and prognostic significance. In fact, compared to non-sloughing tumors, GC exhibiting intragastric exfoliation was recently associated with an aggressive tumor phenotype (characterized by deeper infiltration of the gastric wall, lymph nodal or distant metastases, angiolymphatic and perineural invasion) and poorer prognosis. Adoption of IEC examination in routine practice might help identify patients at higher risk of developing local recurrence and peritoneal metastasis from early and advanced GC, optimizing their treatment and improving quality of life and life expectancy.


Assuntos
Citodiagnóstico/métodos , Recidiva Local de Neoplasia/diagnóstico por imagem , Neoplasias Gástricas/diagnóstico por imagem , Estômago/diagnóstico por imagem , Endoscopia , Humanos , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/patologia , Peritônio/diagnóstico por imagem , Peritônio/patologia , Prognóstico , Estômago/patologia , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia
12.
Anticancer Res ; 39(8): 4111-4116, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31366495

RESUMO

BACKGROUND/AIM: We investigated whether the expression of inositol 1, 4, 5-trisphosphate receptor-binding protein released with inositol 1, 4, 5-trisphosphate (IRBIT) in clinical gastric cancer (GC) patients could predict the therapeutic response to postoperative adjuvant chemotherapy. MATERIALS AND METHODS: Immunohistochemistry was used to investigate IRBIT expression in 115 GC patients. To clarify whether IRBIT had a relationship with the therapeutic effects of chemotherapy, we compared two groups - 62 patients treated with postoperative adjuvant chemotherapy and 53 patients treated with postoperative adjuvant chemotherapy. RESULTS: Regarding the postoperative adjuvant chemotherapy-free group, we did not find any statistically significant correlation between clinicopathological features and recurrence regardless of the expression of IRBIT. In contrast, in the group receiving postoperative adjuvant chemotherapy, a significant association was found between IRBIT expression and both overall and disease-free survival. CONCLUSION: IRBIT may be used as a useful predictive marker for chemotherapy.


Assuntos
Biomarcadores Tumorais/genética , Lectinas Tipo C/genética , Proteínas de Membrana/genética , Recidiva Local de Neoplasia/tratamento farmacológico , Neoplasias Gástricas/tratamento farmacológico , Idoso , Quimioterapia Adjuvante/efeitos adversos , Intervalo Livre de Doença , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/patologia , Fosforilação/efeitos dos fármacos , Ligação Proteica/efeitos dos fármacos , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia
13.
J Cancer Res Clin Oncol ; 145(10): 2481-2493, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31451931

RESUMO

PURPOSE: Pancreatic adenocarcinoma (PAC) represents one of the most fatal types of cancer with an exceptionally poor prognosis, underscoring the need for improved diagnostic and treatment approaches. An over-expression of somatostatin receptors (SST) as well as of the chemokine receptor CXCR4 has been shown for many tumour entities. Respective expression data for PAC, however, are scarce and contradictory. METHODS: Overall, 137 tumour samples from 70 patients, 26 of whom were diagnosed with PAC and 44 with pancreatic neuroendocrine tumour (PanNET), were compared in terms of SST and CXCR4 expression by immunohistochemical analysis using well-characterized rabbit monoclonal antibodies. RESULTS: Only SST1 and CXCR4 expression was detected in PAC tumours, with SST1 present in 42.3% and CXCR4 in 7.7% of cases. However, the overall staining intensity was very weak. In contrast to the tumour cells, in many PAC cases, tumour capillaries exhibited strong SST3, SST5, or CXCR4 expression. In PanNETs, SST2 was the most-prominently expressed receptor, observed in 75.0% of the tumours at medium-strong intensity. SST5, SST1, and CXCR4 expression was detected in 20.5%, 15.9%, and 11.4% of PanNET cases, respectively, but the staining intensity was only weak. SST2 positivity in PanNET, but not in PAC, was associated with favourable patient outcomes. CONCLUSIONS: SST or CXCR4 expression in PAC is clearly of no therapeutic relevance. However, indirect targeting of these tumours via SST3, SST5, or CXCR4 on tumour microvessels may represent a promising additional therapeutic strategy.


Assuntos
Adenocarcinoma/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Intestinais/genética , Tumores Neuroendócrinos/genética , Neoplasias Pancreáticas/genética , Receptores CXCR4/genética , Somatostatina/genética , Neoplasias Gástricas/genética , Adenocarcinoma/metabolismo , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Adulto , Idoso , Biomarcadores , Linhagem Celular Tumoral , Feminino , Perfilação da Expressão Gênica , Humanos , Imuno-Histoquímica , Neoplasias Intestinais/metabolismo , Neoplasias Intestinais/mortalidade , Neoplasias Intestinais/patologia , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Tumores Neuroendócrinos/metabolismo , Tumores Neuroendócrinos/mortalidade , Tumores Neuroendócrinos/patologia , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/patologia , Receptores CXCR4/metabolismo , Somatostatina/metabolismo , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia
14.
Oncol Rep ; 42(4): 1283-1294, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31364750

RESUMO

Carboxypeptidase X, M14 family member 2 (CPXM2), has been associated with several human disorders such as developmental diseases. However, whether CPXM2 is involved in oncogenesis or tumor progression remains unclear. In the present study, we used clinical samples from gastric cancer (GC) patients to investigate potential roles of CPXM2 in GC. We also analyzed datasets from the Oncomine database, The Cancer Genome Atlas (TCGA), and the Kaplan­Meier Plotter to validate these results. We found that CPXM2 was overexpressed in GC and that the overexpression was associated with an unfavorable prognosis, regardless of the Lauren classification and tumor node metastasis staging. In addition, knockdown of CPXM2 in cultured GC cells significantly impeded cell proliferation and migration, as indicated by the cholecystokinin octapeptide, colony formation assay, scratch wound healing assay, and Transwell® migration assay. Furthermore, gene set enrichment analysis using RNA­seq data from TCGA indicated that high CPXM2 expression in GC patients was positively correlated with the HALLMARK_APICAL_JUNCTION and HALLMARK_EPITHELIAL_MESENCHYMAL_TRANSITION gene sets. Finally, western blotting results revealed that several key molecules involved in the epithelial mesenchymal transition were regulated by CPXM2. Taken together, these results imply an active role for CPXM2 in promoting tumor aggressiveness via epithelial to mesenchymal transition (EMT) modulation in GCs.


Assuntos
Carboxipeptidases/biossíntese , Neoplasias Gástricas/enzimologia , Neoplasias Gástricas/patologia , Idoso , Carboxipeptidases/genética , Carboxipeptidases/metabolismo , Linhagem Celular Tumoral , Movimento Celular/fisiologia , Proliferação de Células/fisiologia , Transição Epitelial-Mesenquimal , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Neoplasias Gástricas/genética , Regulação para Cima
15.
DNA Cell Biol ; 38(10): 1147-1154, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31453724

RESUMO

RASSF2 is a tumor suppressor gene closely related to gastric cancer. This meta-analysis was designed to assess the quality in the previous studies and establish the value of RASSF2 methylation in the prediction and prognosis of gastric cancer. The eligible literatures with publication deadline of May 3, 2019 were collected from PubMed, EMBASE, CNKI, Wanfang, and CNVIP databases. The correlation between RASSF2 methylation level and gastric cancer was estimated by odds ratio and 95% confidence interval (OR and 95% CI) values. A total of eight articles were included in the study. A total of 517 gastric cancer tissue samples and 517 adjacent nontumor tissue samples were included. The results of the analysis showed that RASSF2 had a significantly higher level of methylation in gastric cancer (OR = 17.56, 95% CI = 7.11-43.35, p-value = 0.009). Meanwhile, we tested whether there was association of RASSF2 methylation with tumor metastasis, and we also analyzed whether there was a gender difference in RASSF2 methylation. However, our results showed no statistical significance of the two aforementioned tests (p > 0.1). Our study suggested that RASSF2 methylation could predict the risk of gastric cancer. However, it might not be feasible for the prediction of tumor metastasis.


Assuntos
Metilação de DNA , Epigênese Genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Gástricas/diagnóstico , Proteínas Supressoras de Tumor/genética , Feminino , Humanos , Metástase Linfática , Masculino , Razão de Chances , Prognóstico , Risco , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia , Proteínas Supressoras de Tumor/metabolismo
16.
Braz J Med Biol Res ; 52(8): e8341, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31365693

RESUMO

MicroRNAs (miRNAs), as post-transcriptional regulators, have been reported to be involved in the initiation and progression of various types of cancer, including gastric cancer (GC). The present study aimed to investigate the role of miR-383-5p in gastric carcinogenesis. Cell viability was analyzed using CCK-8 kit. Annexin V-fluorescein isothiocyanate/propidium iodide double staining was used to evaluate cell apoptosis. The expression levels of miR-383-5p and histone deacetylase 9 (HDAC9) mRNA in GC tissues and cell lines were analyzed using RT-qPCR. The protein expression of HDAC9 was detected by western blotting. We found that HDAC9 was up-regulated and miR-383-5p was down-regulated in GC tissues and cell lines. High HDAC9 expression or low miR-383-5p expression was closely related to poor prognosis and metastasis in GC patients. HDAC9 knockout or miR-383-5p mimics led to growth inhibition and increased apoptosis in AGS and SGC-7901 cells. More importantly, we validated that miR-383-5p as a post-transcriptional regulator inhibited HDAC9 expression and was inversely correlated with HDAC9 expression in GC tissues. miR-383-5p had the opposite effects to HDAC9 in gastric carcinogenesis. miR-383-5p played an important role in gastric carcinogenesis, and it is one of the important mechanisms to regulate oncogenic HDAC9 in GC, which might be helpful in the development of novel therapeutic strategies for the treatment of GC.


Assuntos
Carcinoma/patologia , Histona Desacetilases/metabolismo , MicroRNAs/metabolismo , Proteínas Repressoras/metabolismo , Neoplasias Gástricas/patologia , Apoptose , Carcinogênese/genética , Carcinoma/genética , Carcinoma/metabolismo , Proliferação de Células/genética , Progressão da Doença , Regulação para Baixo , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , RNA Mensageiro/metabolismo , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo
17.
DNA Cell Biol ; 38(9): 1005-1012, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31335180

RESUMO

Long noncoding RNA (lncRNA) was closely attached to various cancers according to previous studies. In this study we aimed to investigate an lncRNA signature with prognostic value of over survival (OS) outcomes of gastric cancer (GC). Profiles of mRNAs expression and clinical information of 381 GC tissues and 32 nontumor gastric tissues were downloaded from The Cancer Genome Atlas database. Comparison of various lncRNA expression between cancer tissue and normal tissue was made among these data. In the end, a nine-lncRNA signature was discovered using univariate and multivariate Cox regression analyses, with a prospect possibility of the OS in GC patients. Receiver operating characteristic (ROC) was used to evaluate the accuracy of survival model. The gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were used to predict the possible functions and pathways of these lncRNAs. Altogether 720 distinctively expressed lncRNAs were selected between GC and normal tissues. By univariate and multivariate Cox regression analyses, nine lncRNAs were eventually filtered to set a predictive model, distributing patients into high-risk and low-risk groups with extraordinary different OS. Area under the curve of the ROC curve for the nine-lncRNA signature's prediction of 5-year OS was 0.795. Further functional enrichment analyses indicated that these lncRNAs may be associated with biological processes such as protein binding, DNA replication, and cell cycle. Our study identified a nine-lncRNA signature, which could act as a potential prognostic biomarker in the prediction of GC patients' OS.


Assuntos
Biomarcadores Tumorais/genética , RNA Longo não Codificante/genética , Neoplasias Gástricas/genética , Idoso , Biomarcadores Tumorais/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , RNA Longo não Codificante/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia , Análise de Sobrevida , Transcriptoma
18.
Yonsei Med J ; 60(8): 720-726, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31347326

RESUMO

PURPOSE: The purpose of this study was to explore the potential early diagnostic value of serum microRNA-381(miRNA-381) in patients with gastric cancer (GC). MATERIALS AND METHODS: Patients with advanced gastric cancer (AGC) and early gastric cancer (EGC), as well as healthy individuals, were enrolled in this study. Expression of miRNA-381 in serum was detected using real-time quantitative PCR. Electrochemiluminescence analysis was used to investigate the expression of classic tumor markers, including carbohydrate antigen (CA) 199, CA724, and carcinoembryonic antigen. Finally, receiver operating characteristic curve and Kaplan-Meier analysis were used to determine the value of miRNA-381 in clinical diagnosis of GC. RESULTS: miRNA-381 was differentially expressed among the study groups. AUC analysis showed that the sensitivity and specificity of serum miRNA-381 in the diagnosis of GC were superior to those of other tumor markers. Furthermore, low levels of miRNA-381 expression were positively correlated with lymph node metastasis and AGC. Finally, Kaplan-Meier survival analysis showed that down-regulation of miRNA-381 was associated with lymph node metastasis and the development of GC. CONCLUSION: miRNA381, which was down-regulated in GC, might be a novel early diagnosis marker for patients with GC.


Assuntos
Biomarcadores Tumorais/sangue , Detecção Precoce de Câncer , MicroRNAs/sangue , Neoplasias Gástricas/sangue , Neoplasias Gástricas/diagnóstico , Área Sob a Curva , Antígeno Carcinoembrionário/sangue , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Curva ROC , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia
19.
Medicine (Baltimore) ; 98(27): e16273, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31277152

RESUMO

BACKGROUND: Although the outcome of patients with gastric cancer (GC) has improved significantly with the recent implementation of annual screening programs. Reliable prognostic biomarkers are still needed due to the disease heterogeneity. Increasing pieces of evidence revealed an association between immune signature and GC prognosis. Thus, we aim to build an immune-related signature that can estimate prognosis for GC. METHODS: For identification of a prognostic immune-related gene signature (IRGS), gene expression profiles and clinical information of patients with GC were collected from 3 public cohorts, divided into training cohort (n = 300) and 2 independent validation cohorts (n = 277 and 433 respectively). RESULTS: Within 1811 immune genes, a prognostic IRGS consisting of 16 unique genes was constructed which was significantly associated with survival (hazard ratio [HR], 3.9 [2.78-5.47]; P < 1.0 × 10). In the validation cohorts, the IRGS significantly stratified patients into high- vs low-risk groups in terms of prognosis across (HR, 1.84 [1.47-2.30]; P = 6.59 × 10) and within subpopulations with stage I&II disease (HR, 1.96 [1.34-2.89]; P = 4.73 × 10) and was prognostic in univariate and multivariate analyses. Several biological processes, including TGF-ß and EMT signaling pathways, were enriched in the high-risk group. T cells CD4 memory resting and Macrophage M2 were significantly higher in the high-risk risk group compared with the low-risk group. CONCLUSION: In short, we developed a prognostic IRGS for estimating prognosis in GC, including stage I&II disease, providing new insights into the identification of patients with GC with a high risk of mortality.


Assuntos
Biomarcadores Tumorais/imunologia , DNA de Neoplasias/genética , Perfilação da Expressão Gênica/métodos , Regulação Neoplásica da Expressão Gênica , Neoplasias Gástricas/genética , Transcriptoma/genética , Biomarcadores Tumorais/genética , DNA de Neoplasias/imunologia , Feminino , Humanos , Masculino , Prognóstico , Fatores de Risco , Neoplasias Gástricas/imunologia , Neoplasias Gástricas/metabolismo
20.
BMC Bioinformatics ; 20(1): 396, 2019 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-31315558

RESUMO

BACKGROUND: Since the number of known lncRNA-disease associations verified by biological experiments is quite limited, it has been a challenging task to uncover human disease-related lncRNAs in recent years. Moreover, considering the fact that biological experiments are very expensive and time-consuming, it is important to develop efficient computational models to discover potential lncRNA-disease associations. RESULTS: In this manuscript, a novel Collaborative Filtering model called CFNBC for inferring potential lncRNA-disease associations is proposed based on Naïve Bayesian Classifier. In CFNBC, an original lncRNA-miRNA-disease tripartite network is constructed first by integrating known miRNA-lncRNA associations, miRNA-disease associations and lncRNA-disease associations, and then, an updated lncRNA-miRNA-disease tripartite network is further constructed through applying the item-based collaborative filtering algorithm on the original tripartite network. Finally, based on the updated tripartite network, a novel approach based on the Naïve Bayesian Classifier is proposed to predict potential associations between lncRNAs and diseases. The novelty of CFNBC lies in the construction of the updated lncRNA-miRNA-disease tripartite network and the introduction of the item-based collaborative filtering algorithm and Naïve Bayesian Classifier, which guarantee that CFNBC can be applied to predict potential lncRNA-disease associations efficiently without entirely relying on known miRNA-disease associations. Simulation results show that CFNBC can achieve a reliable AUC of 0.8576 in the Leave-One-Out Cross Validation (LOOCV), which is considerably better than previous state-of-the-art results. Moreover, case studies of glioma, colorectal cancer and gastric cancer demonstrate the excellent prediction performance of CFNBC as well. CONCLUSIONS: According to simulation results, due to the satisfactory prediction performance, CFNBC may be an excellent addition to biomedical researches in the future.


Assuntos
Doença/genética , RNA Longo não Codificante/metabolismo , Algoritmos , Teorema de Bayes , Neoplasias Colorretais/genética , Simulação por Computador , Glioma/genética , Humanos , MicroRNAs/metabolismo , Neoplasias Gástricas/genética
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA