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1.
Aging (Albany NY) ; 12(1): 156-177, 2020 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-31896739

RESUMO

A promising new strategy for cancer therapy is to target the autophagic pathway. However, comprehensive characterization of autophagy genes and their clinical relevance in cancer is still lacking. Here, we systematically characterized alterations of autophagy genes in multiple cancer lines by analyzing data from The Cancer Genome Atlas and CellMiner database. Interactions between autophagy genes and clinically actionable genes (CAGs) were identified by analyzing co-expression, protein-protein interactions (PPIs) and transcription factor (TF) data. A key subnetwork was identified that included 18 autophagy genes and 22 CAGs linked by 28 PPI pairs and 1 TF-target pair, which was EGFR targeted by RARA. Alterations in the expression of autophagy genes were associated with patient survival in multiple cancer types. RARA and EGFR were associated with worse survival in colorectal cancer patients. The regulatory role of EGFR in 5-FU resistance was validated in colon cancer cells in vivo and in vitro. EGFR contributed to 5-FU resistance in colon cancer cells through autophagy induction, and EGFR overexpression in 5-FU resistant colon cancer was regulated by RARA. The present study provides a comprehensive analysis of autophagy in different cancer cell lines and highlights the potential clinical utility of targeting autophagy genes.

2.
Nat Commun ; 10(1): 5190, 2019 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-31729389

RESUMO

As one of next-generation semiconductors, hybrid halide perovskites with tailorable optoelectronic properties are promising for photovoltaics, lighting, and displaying. This tunability lies on variable crystal structures, wherein the spatial arrangement of halide octahedra is essential to determine the assembly behavior and materials properties. Herein, we report to manipulate their assembling behavior and crystal dimensionality by locally collective hydrogen bonding effects. Specifically, a unique urea-amide cation is employed to form corrugated 1D crystals by interacting with bromide atoms in lead octahedra via multiple hydrogen bonds. Further tuning the stoichiometry, cations are bonded with water molecules to create a larger spacer that isolates individual lead bromide octahedra. It leads to zero-dimension (0D) single crystals, which exhibit broadband 'warm' white emission with photoluminescence quantum efficiency 5 times higher than 1D counterpart. This work suggests a feasible strategy to modulate the connectivity of octahedra and consequent crystal dimensionality for the enhancement of their optoelectronic properties.

3.
Chem Commun (Camb) ; 55(89): 13406-13409, 2019 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-31637391

RESUMO

A new small molecular hole-transporting material, 1,3,6,8-tetrakis[N-(p-methoxyphenyl)-N'-(9,9'-dimethyl-9H-fluoren-2-yl)-amino]pyrene (TFAP) was synthesized and applied in CH3NH3PbI3-perovskite solar cells. A best power conversion efficiency of 19.7% with a photovoltage of 1.11 V has been achieved.

4.
ACS Appl Mater Interfaces ; 10(48): 41592-41598, 2018 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-30406985

RESUMO

By introducing six triarylamine groups to a hexaphenylbenzene (HPB) or a hexakis(2-thienyl)benzene (HTB) core, two propeller-shaped, triarylamine-rich, and low-cost hole-transporting materials (HTMs), which are termed as HPB-OMe and HTB-OMe, respectively, with considerable hole mobility, were obtained by easy synthetic routes. Solid-state planar perovskite CH3NH3PbI3 solar cells (PSCs) with two new HTMs showed high power conversion efficiencies (12.9% for HPB-OMe and 17.3% for HTB-OMe in forward scans) under standard 100 mW cm-2 AM 1.5G illumination without doping. A comparison of matched-degree of energy levels, hole-transporting ability, photovoltaic conversion efficiencies, and recombination of the two HTMs indicated that developing multi-triarylamine- and thiophene-rich molecules provides candidate and efficient dopant-free HTMs for PSCs.

5.
Clin Chim Acta ; 487: 357-362, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30296444

RESUMO

BACKGROUND: Many studies have demonstrated that right-sided colon cancer (RCC) has a higher mortality rate and worse prognosis than left-sided colon cancer (LCC). However, the underlying biological mechanism that can account for these differences is unclear. METHODS: In this study, plasma metabolic profiles in 147 LCC patients and 105 RCC patients were systematically analyzed by the ultra high performance liquid chromatography quadruple time-of-flight mass spectrometry (UHPLC-QTOF/MS) platform in conjunction with univariate and multivariate statistical analysis. RESULTS: Metabolic signatures revealed considerable differences between patients with RCC and LCC, and clear separations were observed between the two groups in partial least-squares discriminant analysis score plots. In total, six metabolites were identified as potential metabolite markers for tumor location in RCC compared with LCC, including upregulated trimethylamine N-oxide and indoxyl sulfate, and downregulated anserine, L-targinine, gamma-glutamyl-gamma-aminobutyraldehyde and pyridoxal 5'-phosphate. These differences highlight that significant alternations occur in the pathways of methane metabolism, arginine and proline metabolism, histidine metabolism, beta-alanine metabolism and vitamin B6 metabolism in RCC compared with LCC. CONCLUSIONS: Identified biomarkers and metabolic pathways may facilate our understanding of the different mortality rates and prognoses between RCC and LCC.


Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias do Colo/metabolismo , Metabolômica , Biomarcadores Tumorais/sangue , Cromatografia Líquida de Alta Pressão , Neoplasias do Colo/sangue , Neoplasias do Colo/diagnóstico , Feminino , Humanos , Masculino , Espectrometria de Massas , Pessoa de Meia-Idade , Análise Multivariada
6.
ACS Omega ; 3(9): 10791-10797, 2018 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-31459193

RESUMO

The simpler the design, the better and more effective it is. Two novel conjugated triarylamine derivatives in donor-π-donor structure employing biphenyl core and pyrene core as π-bridges, which are termed as Bp-OMe and Py-OMe, have been synthesized and characterized and then applied to perovskite solar cells (PSCs) as hole-transport materials (HTMs) successfully. Using 2,2',7,7'-tetrakis(N,N-di-p-methoxy-phenylamine)-9,9'-spirobiuorene (spiro-OMeTAD) as a relative reference, Py-OMe-based PSCs showed the best power conversion efficiency (PCE) of 19.28% under AM 1.5 G illumination at 100 mW cm-2, which is comparable to that of PSCs based on spiro-OMeTAD with a best PCE of 18.57% with doping. Although Bp-OMe-based PSCs performed with relatively poor PCEs (best PCE of 15.06%) than those of Py-OMe-based PSCs, attributing to the poor planarity and hole mobility, taking the cost into consideration, Bp-OMe and Py-OMe are much more likely to be promising efficient HTMs for PSCs.

7.
Metabolomics ; 14(9): 110, 2018 08 16.
Artigo em Inglês | MEDLINE | ID: mdl-30830371

RESUMO

INTRODUCTION: Colorectal cancer (CRC) is a clinically heterogeneous disease, which necessitates a variety of treatments and leads to different outcomes. Only some CRC patients will benefit from neoadjuvant chemotherapy (NACT). OBJECTIVES: An accurate prediction of response to NACT in CRC patients would greatly facilitate optimal personalized management, which could improve their long-term survival and clinical outcomes. METHODS: In this study, plasma metabolite profiling was performed to identify potential biomarker candidates that can predict response to NACT for CRC. Metabolic profiles of plasma from non-response (n = 30) and response (n = 27) patients to NACT were studied using UHPLC-quadruple time-of-flight)/mass spectrometry analyses and statistical analysis methods. RESULTS: The concentrations of nine metabolites were significantly different when comparing response to NACT. The area under the receiver operating characteristic curve value of the potential biomarkers was up to 0.83 discriminating the non-response and response group to NACT, superior to the clinical parameters (carcinoembryonic antigen and carbohydrate antigen 199). CONCLUSION: These results show promise for larger studies that could result in more personalized treatment protocols for CRC patients.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/metabolismo , Metabolômica , Biomarcadores Tumorais/sangue , Cromatografia Líquida de Alta Pressão , Neoplasias Colorretais/sangue , Feminino , Humanos , Masculino , Espectrometria de Massas , Pessoa de Meia-Idade , Terapia Neoadjuvante
8.
Chem Commun (Camb) ; 53(76): 10548-10551, 2017 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-28890960

RESUMO

A simple chemical process was developed in a scalable manner, to reduce trap states in perovskite absorbers from the very beginning. The obvious decrease of I2 in methylammonium iodide and the decrease of trap density in the resultant films were identified, which led to the power conversion efficiency (PCE) of perovskite solar cells (PSCs) increase from 16.5% to 18.5%.

9.
Mol Cancer ; 16(1): 9, 2017 01 13.
Artigo em Inglês | MEDLINE | ID: mdl-28086904

RESUMO

BACKGROUND: With more than 600,000 mortalities each year, colorectal cancer (CRC) is the third most commonly diagnosed type of cancer worldwide. Recently, mechanisms involving noncoding RNAs have been implicated in the development of CRC. METHODS: We examined expression levels of lncRNA CRNDE and miR-181a-5p in 64 cases of CRC tissues and cell lines by qRT-PCR. Gain-of-function and loss-of-function assays were performed to examine the effect of CRNDE and miR-181a-5p on proliferation and chemoresistance of CRC cells. Using fluorescence reporter and western blot assays, we also explored the possible mechanisms of CRNDE in CRC cells. RESULTS: In this study, we found that the expression levels of the CRNDE were upregulated in CRC clinical tissue samples. We identified microRNA miR-181a-5p as an inhibitory target of CRNDE. Both CRNDE knockdown and miR-181a-5p overexpression in CRC cell lines led to inhibited cell proliferation and reduced chemoresistance. We also determined that ß-catenin and TCF4 were inhibitory targets of miR-181a-5p, and that Wnt/ß-catenin signaling was inhibited by both CRNDE knockdown and miR-181a-5p overexpression. Significantly, we found that the repression of cell proliferation, the reduction of chemoresistance, and the inhibition of Wnt/ß-catenin signaling induced by CRNDE knockdown would require the increased expression of miR-181a-5p. CONCLUSIONS: Our study demonstrated that the lncRNA CRNDE could regulate the progression and chemoresistance of CRC via modulating the expression levels of miR-181a-5p and the activity of Wnt/ß-catenin signaling.


Assuntos
Resistencia a Medicamentos Antineoplásicos/genética , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , RNA Longo não Codificante/genética , Via de Sinalização Wnt , Adulto , Idoso , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/genética , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Biológicos , Gradação de Tumores , Metástase Neoplásica , Estadiamento de Neoplasias , Interferência de RNA , Fator de Transcrição 4 , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Carga Tumoral , beta Catenina/genética , beta Catenina/metabolismo
10.
Medicine (Baltimore) ; 96(51): e9068, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29390435

RESUMO

Early neurological deterioration (END) is associated with increased risk of functional disability and mortality. However, data are limited regarding the long-term risk of poor functional outcomes. Thus we explored the association between END and long-term outcomes in patients with acute ischemic stroke.A total of 1064 patients were enrolled with acute ischemic stroke who were consecutively admitted to the 3 stroke units of Huai-He Hospital, Kaifeng, China. END was defined as an increment change of at least one point in motor power or total National Institute of Health Stroke Scale (NIHSS) score deterioration ≥2 points within the first week after admission. We retrospectively assessed the risk factors of END and prospectively explored the relationship between END and the long-term outcomes by multivariable regression models after adjusting the potential confounding factors. Outcomes were evaluated at 18 months based on modified Rankin scale (MRS) scores.Approximately 32% of first-ever ischemic stroke patients experienced END during the acute phase. END was associated with diabetes (odds ratio [OR], 2.218; 95% confidence interval [CI] 1.619-3.037), NIHSS score at admission (OR, 1.052; 95% CI 1.023-1.082), C-reactive protein (CRP) levels (OR, 1.224; 95% CI 1.066-1.406]), and homocysteine (HCY) levels (OR, 1.203; 95% CI 1.061-1.365) after adjusting related factors, such as hypertension, diabetes, NIHSS at admission, and some blood laboratory values, including direct bilirubin, total cholesterol, low-density lipoprotein, glucose, CRP, HCY, and D-dimer levels. During the follow-up period, 52 (4.9%) patients died, 160 (15.0%) recrudesced, and 317 (29.8%) suffered poor outcomes. Multivariate logistic regression analyses revealed that poor outcome was associated with END (OR, 3.366; 95% CI 2.495-4.542), age (OR, 1.028; 95% CI 1.015-1.041), body mass index (OR, 1.096; 95% CI 1.051-1.144), coronary heart disease (OR, 1.637; 95% CI 1.108-2.416), and CRP (OR, 2.474; 95% CI 1.840-3.326).The risk factors of END are multifaceted. Diabetes, NIHSS score at admission, CRP, and HCY are independent predictors of END. In addition, the results of this study indicate that END is an important predictor of poor functional outcome.


Assuntos
Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/mortalidade , Fatores Etários , Índice de Massa Corporal , Proteína C-Reativa/análise , China/epidemiologia , Doença das Coronárias/mortalidade , Complicações do Diabetes , Progressão da Doença , Feminino , Homocisteína/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estudos Retrospectivos , Fatores de Risco
11.
Am J Transl Res ; 8(10): 4405-4414, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27830024

RESUMO

PURPOSE: This study aims to investigate the expression and clinical significance of p190RhoGAP, a member of the RhoGAP family, in colorectal cancer (CRC). METHODS: The expression p190RhoGAP was detected by RT-PCR, western blot (WB) and immunohistochemistry (IHC) in 14 paired CRCs and matched non-cancerous mucosal tissues. The protein content of p190RhoGAP was identified in 114 CRCs by IHC. In addition, the association of the expression of p190RhoGAP with carcinogenesis, distant metastasis and prognosis was further evaluated. RESULTS: In 14 paired fresh tissues, the mRNA (P<0.0001) and protein (P = 0.003) expression levels of p190RhoGAP were significantly higher in primary CRCs than in paired non-cancerous mucosal tissues; and was consistent with WB results. The expression of p190RhoGAP increased from normal mucosa to adenoma, and became even greater in primary carcinoma (P = 0.001). The expression level of p190RhoGAP was highest in liver metastasis compared to primary carcinoma (P = 0.028). The incidence of p190RhoGAP expression-positive cases was 58.77% in 114 CRC tissues. Furthermore, the enhanced expression of p190RhoGAP was significantly associated with shorter disease-specific survival (P<0.001) and shorter disease-free survival (P<0.001). Cox regression analysis indicated that p190RhoGAP was an independent prognostic parameter for CRC. CONCLUSION: p190RhoGAP may be an independent predictive factor for the prognosis of CRC, and the abnormal expression of p190RhoGAP may play a crucial role in colorectal carcinogenesis and distant metastasis.

12.
Chem Rec ; 16(2): 754-67, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26853768

RESUMO

Monometallic and dimetallic complexes with the ruthenium-amine conjugated structural unit have been prepared. These complexes display consecutive redox waves with low potentials and rich and intense absorptions in the near-infrared region. The electrochemical and spectroscopic properties can be modulated using substituents or auxiliary ligands with different electronic natures. Through simple functionalization, electropolymerized or monolayer thin films of these complexes have been prepared. These films display multistate near-infrared electrochromism with good contrast ratios and long optical retention times. In addition, flip-flop and flip-flap-flop memories have been demonstrated on the basis of these thin films.

13.
Tumour Biol ; 37(6): 7657-65, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26687759

RESUMO

RNA-binding protein Lin28A is frequently over-expressed in human malignant tumors and is associated with tumor advance and poor prognosis. However, the expression pattern and functions of Lin28A in colon cancer are unknown. In this study, we detected the expression of Lin28A in colon cancer patients and tested the effect of Lin28A on the chemotherapeutic sensitivity of colon cancer cells to 5-fluorouracil (5-FU). As expected, we showed that Lin28A is up-regulated in 73.3 % of colon cancer patients. However, to our surprise, we found that oncogenic protein Lin28A-enforced expression in colon cancer cells enhanced the chemosensitivity of cancer cells to 5-FU via promoting the cell apoptosis. Further mechanisms study revealed that the effect of Lin28A increasing chemosensitivity of cancer cells is in a let-7 independent manner, but which is associated with decreasing the expression of DNA damage repair protein H2AX. Conclusively, here we reported an unexpected function of Lin28A, which may shed lights on fully understanding the physiological and pathological roles of this oncogene.


Assuntos
Adenocarcinoma/tratamento farmacológico , Antimetabólitos Antineoplásicos/farmacologia , Apoptose/genética , Neoplasias do Colo/tratamento farmacológico , Fluoruracila/farmacologia , Proteínas de Neoplasias/fisiologia , Proteínas de Ligação a RNA/fisiologia , Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Adulto , Idoso , Apoptose/efeitos dos fármacos , Neoplasias do Colo/genética , Neoplasias do Colo/metabolismo , Neoplasias do Colo/patologia , Reparo do DNA/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos , Feminino , Células HCT116 , Histonas/biossíntese , Histonas/genética , Humanos , Masculino , MicroRNAs/fisiologia , Pessoa de Meia-Idade , Proteínas de Neoplasias/biossíntese , Proteínas de Neoplasias/genética , RNA Neoplásico/fisiologia , Proteínas de Ligação a RNA/biossíntese , Proteínas de Ligação a RNA/genética , Proteínas Recombinantes de Fusão/biossíntese , Proteínas Recombinantes de Fusão/genética , Método Simples-Cego
14.
Int J Clin Exp Pathol ; 8(6): 7092-101, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26261602

RESUMO

Circulating microRNAs (miRNAs) were recognized to be potential non-invasive biomarkers for colorectal cancer (CRC) detection and prediction. Meanwhile, the association of the expression of plasma miRNAs with the risk of CRC patients has rarely been analyzed. Therefore, we conducted this study to evaluate the value of plasma miRNAs for CRC diagnosis and risk estimation. Fasting blood samples from 100 CRC patients and 79 cancer-free controls were collected. Plasma miR-106a, miR-20a, miR-27b, miR-92a and miR-29a levels were detected by RT-qPCR. Sensitivity and specificity were employed to evaluate the diagnostic value of miRNAs for CRC. Univariate and multivariate logistic regression were employed to analyze the association between miRNAs expression and CRC risk. As results, miR-106a and miR-20a were elevated in the patients with CRC. The sensitivity of miR-106a was 74.00% and the specificity was 44.40%, while the cutoff value was 2.03. As for miR-20a, the sensitivity was 46.00% and specificity was 73.42% when employed 2.44 as cutoff value. High expression of plasma miR-106a increased CRC risk by 1.80 -fold. Plasma miR-106a and miR-20a may as noninvasive biomarkers for detecting the CRC. High expression of miR-106a associated with CRC risk.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/genética , Testes Genéticos/métodos , MicroRNAs/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Área Sob a Curva , Biomarcadores Tumorais/sangue , Estudos de Casos e Controles , Distribuição de Qui-Quadrado , Neoplasias Colorretais/sangue , Neoplasias Colorretais/patologia , Feminino , Humanos , Modelos Logísticos , Masculino , MicroRNAs/sangue , Pessoa de Meia-Idade , Análise Multivariada , Razão de Chances , Valor Preditivo dos Testes , Prognóstico , Curva ROC , Reação em Cadeia da Polimerase em Tempo Real , Reprodutibilidade dos Testes , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Medição de Risco , Fatores de Risco
15.
Angew Chem Int Ed Engl ; 54(32): 9192-7, 2015 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-26138863

RESUMO

A diruthenium complex with a redox-active amine bridge has been designed, synthesized, and studied by single-crystal X-ray analysis and DFT and TDDFT calculations. It shows three well-separated redox processes with exclusive near-infrared (NIR) absorbance at each redox state. The electropolymerized film of a related vinyl-functionalized complex displays multistate NIR electrochromism with low operational potential, good contrast ratio, and long retention time. Flip-flop, flip-flap-flop, and ternary memories have been realized by using the obtained film (ca. 15-20 nm thick) with three electrochemical inputs and three NIR optical outputs that each displays three levels of signal intensity.

16.
Dalton Trans ; 44(34): 15244-9, 2015 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-25986241

RESUMO

Hybrid films of functional molecules and metal nanoparticles have been considered to be novel photo-functional devices. Here we have successfully constructed hybrid films of silver nanoparticles and ruthenium polypyridine derivatives on substrates. In order to hybridise them on a surface, a self-assembled monolayer method via chemical bond formation and electro-reductive polymerisation (thick layers) via physical attachment have been employed. These methods have the advantage of convenient and reproducible fabrication of complicated hybrid films. Furthermore, it has been clarified that these hybrid films show unique photo-functional behaviours, such as enhanced photocurrent generation.

17.
J Am Chem Soc ; 137(12): 4058-61, 2015 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-25775114

RESUMO

Self-assembled monolayer films of a cyclometalated ruthenium complex with a redox-active amine substituent and three carboxylic acid groups have been prepared on ITO electrode surfaces. The obtained thin films show three-state electrochromic switching with low electrochemical potential inputs and high near-infrared absorbance outputs. Thanks to the long retention time of each oxidation states, these films have been used to demonstrate surface-confined flip-flop memory functions with high ON/OFF ratios at the molecular scale.

18.
Chem Sci ; 6(2): 1308-1315, 2015 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-29560217

RESUMO

A diruthenium complex capped with two triphenylamine units was polymerized by electrochemical oxidation to afford metallopolymeric films with alternating diruthenium and tetraphenylbenzidine structures. The obtained thin films feature rich redox processes associated with the reduction of the bridging ligands (tetra(pyrid-2-yl)pyrazine) and the oxidation of the tetraphenylbenzidine and diruthenium segments. The sandwiched ITO/polymer film/Al electrical devices show excellent resistive memory switching with a low operational voltage, large ON/OFF current ratio (100-1000), good stability (500 cycles tested), and long retention time. In stark contrast, devices with polymeric films of a related monoruthenium complex show poor memory performance. The mechanism of the field-induced conductivity of the diruthenium polymer film is rationalized by the formation of a charge transfer state, as supported by DFT calculations.

19.
J Cancer Res Clin Oncol ; 141(4): 661-9, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25326896

RESUMO

BACKGROUND AND OBJECTIVES: Enhancer of zeste 2 (EZH2), embryonic ectoderm development (EED), and suppressor of zeste 12 homolog (SUZ12), the key component of polycomb repressive complex 2, are of great importance in human cancer pathogenesis. This study was designed to investigate the clinical and prognostic significances of EZH2, EED and SUZ12 in colorectal cancer (CRC) patients. METHODS: The expression of EZH2, EED and SUZ12 mRNA was evaluated in 82 primary CRC and paired non-cancerous mucosa samples by qRT-PCR. RESULTS: We found that overall EZH2, EED and SUZ12 mRNA expression in the CRC tissues was significantly increased than in the non-cancerous tissue (p < 0.05). Increased EZH2, EED and SUZ12 mRNA expression was directly correlated with primary tumor size, regional lymph node metastases, distant metastasis and AJCC stage. Furthermore, CRC patients with higher level of EED, SUZ12 or EZH2 showed a worse disease-free survival (DFS) (p < 0.01). In multivariate analysis, the increased EZH2 expression may be a risk factor for the patients' 3-year DFS (HR 2.517; 95% CI 1.104, 5.736; p = 0.028). Furthermore, the k-means cluster analysis showed that high mRNA expression of EED, SUZ12 and EZH2 was significantly correlated with the aggressive clinical behavior and poor prognosis. CONCLUSIONS: High expression of EED, SUZ12 and EZH2 might contribute to the CRC development/progression.


Assuntos
Neoplasias Colorretais/genética , Regulação Neoplásica da Expressão Gênica , Complexo Repressor Polycomb 2/genética , Western Blotting , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Progressão da Doença , Proteína Potenciadora do Homólogo 2 de Zeste , Humanos , Estimativa de Kaplan-Meier , Metástase Linfática , Análise Multivariada , Estadiamento de Neoplasias , Complexo Repressor Polycomb 2/metabolismo , Prognóstico , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa
20.
Biomed Res Int ; 2014: 236361, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25243122

RESUMO

PURPOSE: To investigate the association between CpG island methylator phenotype (CIMP) and the overall survival of sporadic colorectal cancer (CRC) in Northeast China. METHODS: 282 sporadic CRC patients were recruited in this study. We selected MLH1, MGMT, p16, APC, MINT1, MINT31, and RUNX3 as the CIMP panel markers. The promoter methylation was assessed by methylation sensitive high resolution melting (MS-HRM). Proportional hazards-regression models were fitted with computing hazard ratios (HR) and the corresponding 95% confidence intervals (95% CI). RESULTS: 12.77% (36/282) of patients were CIMP-0, 74.1% (209/282) of patients were CIMP-L, and 13.12% (37/282) of patients were CIMP-H. The five-year survival of the 282 CRC patients was 58%. There was significant association between APC gene promoter methylation and CRC overall survival (HR = 1.61; 95% CI: 1.05-2.46; P = 0.03). CIMP-H was significantly associated with worse prognosis compared to CIMP-0 (HR = 3.06; 95% CI: 1.19-7.89; P = 0.02) and CIMP-L (HR = 1.97; 95% CI: 1.11-3.48; P = 0.02), respectively. While comparing with the combine of CIMP-L and CIMP-0 (CIMP-L/0), CIMP-H also presented a worse prognosis (HR = 2.31; 95% CI: 1.02-5.24; P = 0.04). CONCLUSION: CIMP-H may be a predictor of a poor prognosis of CRC in Northeast China patients.


Assuntos
Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Ilhas de CpG/genética , Metilação de DNA/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , China , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Fenótipo , Prognóstico , Regiões Promotoras Genéticas , Análise de Sobrevida
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