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1.
BMC Bioinformatics ; 21(Suppl 14): 359, 2020 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-32998692

RESUMO

BACKGROUND: The abundance of molecular profiling of breast cancer tissues entailed active research on molecular marker-based early diagnosis of metastasis. Recently there is a surging interest in combining gene expression with gene networks such as protein-protein interaction (PPI) network, gene co-expression (CE) network and pathway information to identify robust and accurate biomarkers for metastasis prediction, reflecting the common belief that cancer is a systems biology disease. However, controversy exists in the literature regarding whether network markers are indeed better features than genes alone for predicting as well as understanding metastasis. We believe much of the existing results may have been biased by the overly complicated prediction algorithms, unfair evaluation, and lack of rigorous statistics. In this study, we propose a simple approach to use network edges as features, based on two types of networks respectively, and compared their prediction power using three classification algorithms and rigorous statistical procedure on one of the largest datasets available. To detect biomarkers that are significant for the prediction and to compare the robustness of different feature types, we propose an unbiased and novel procedure to measure feature importance that eliminates the potential bias from factors such as different sample size, number of features, as well as class distribution. RESULTS: Experimental results reveal that edge-based feature types consistently outperformed gene-based feature type in random forest and logistic regression models under all performance evaluation metrics, while the prediction accuracy of edge-based support vector machine (SVM) model was poorer, due to the larger number of edge features compared to gene features and the lack of feature selection in SVM model. Experimental results also show that edge features are much more robust than gene features and the top biomarkers from edge feature types are statistically more significantly enriched in the biological processes that are well known to be related to breast cancer metastasis. CONCLUSIONS: Overall, this study validates the utility of edge features as biomarkers but also highlights the importance of carefully designed experimental procedures in order to achieve statistically reliable comparison results.


Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/patologia , Máquina de Vetores de Suporte , Área Sob a Curva , Neoplasias da Mama/genética , Feminino , Redes Reguladoras de Genes/genética , Humanos , Modelos Logísticos , Metástase Neoplásica , Mapas de Interação de Proteínas/genética , Curva ROC
2.
Urol Clin North Am ; 47(4): 443-456, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33008495

RESUMO

Cancer vaccines, cytokines, and checkpoint inhibitors are immunotherapeutic agents that act within the cancer immunity cycle. Prostate cancer has provided unique opportunities for, and challenges to, immunotherapy drug development, including low tumor mutational burdens, limited expression of PD-L1, and minimal T-cell intratumoral infiltrates. Nevertheless, efforts are ongoing to help prime prostate tumors by turning a "cold" prostate cancer "hot" and thus rendering them more susceptible to immunotherapy. Combination treatments, use of molecular biomarkers, and use of new immunotherapeutic agents provide opportunities to enhance the immune response to prostate tumors.


Assuntos
Vacinas Anticâncer/uso terapêutico , Fatores Imunológicos/uso terapêutico , Imunoterapia/métodos , Neoplasias da Próstata/patologia , Neoplasias da Próstata/terapia , Idoso , Biomarcadores Tumorais/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/patologia , Estadiamento de Neoplasias , Prognóstico , Neoplasias da Próstata/mortalidade , Medição de Risco , Análise de Sobrevida , Resultado do Tratamento
3.
Tumour Biol ; 42(10): 1010428320963811, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33028151

RESUMO

This study aimed at investigating the expression of candidate microRNAs (miRs), at initial diagnosis, during neoadjuvant chemotherapy, and after the tumor resection in locally advanced breast cancer patients. Plasma samples were collected from locally advanced breast cancer patients (n = 30) and healthy subjects (n = 20) for the detection of candidate miRs' expression using the real-time quantitative polymerase chain reaction. At initial locally advanced breast cancer diagnosis, the expression of miR-21, miR-181a, and miR-10b was significantly increased, whereas that of miR-145 and let-7a was significantly decreased, compared to the healthy individuals. The diagnostic accuracy of miR-21 was superior to both carcinoembryonic antigen and carcinoma antigen 15-3 as diagnostic biomarkers for locally advanced breast cancer. By the end of the treatment, the expression of altered miRs rebound to control values. The expression levels of candidate plasma miRs are useful diagnostic biomarkers, as well as monitoring a proper response for locally advanced breast cancer patients to the treatment. Furthermore, miR-10b and miR-21 can be considered as predictive biomarkers for progression-free survival.


Assuntos
Biomarcadores Tumorais , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/genética , MicroRNA Circulante , MicroRNAs , Adulto , Neoplasias da Mama/mortalidade , Neoplasias da Mama/terapia , Terapia Combinada , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Gradação de Tumores , Metástase Neoplásica , Estadiamento de Neoplasias , Prognóstico , Reação em Cadeia da Polimerase em Tempo Real , Sensibilidade e Especificidade
4.
Medicine (Baltimore) ; 99(41): e22271, 2020 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-33031269

RESUMO

BACKGROUND: This study will summarize the clinical significance of E-Cadherin and ß-catenin in early gastric cancer (EGC). METHODS: Eligible case-control studies were searched from Cochrane Library, PUBMED, EMBASE, PsycINFO, Google Scholar, CBM, and CNKI from inception to the present. In addition, we will also search other sources to avoid missing potential studies. Two authors will independently carry out study selection, data collection, and study methodological quality. A fixed or random-effects model will be utilize to synthesize the data, and RevMan 5.3 software will be used for data analysis. RESULTS: This study will summarize all eligible studies to investigate the clinical significance of E-Cadherin and ß-catenin in EGC. CONCLUSION: The findings of this study may present a genuine understanding of perspective on the clinical significance of E-Cadherin and ß-catenin in EGC.


Assuntos
Biomarcadores Tumorais/metabolismo , Caderinas/metabolismo , Projetos de Pesquisa , Neoplasias Gástricas/metabolismo , beta Catenina/metabolismo , Humanos , Revisões Sistemáticas como Assunto
5.
Nat Commun ; 11(1): 4946, 2020 10 02.
Artigo em Inglês | MEDLINE | ID: mdl-33009409

RESUMO

Immune-related adverse events (irAEs), caused by anti-PD-1/PD-L1 antibodies, can lead to fulminant and even fatal consequences and thus require early detection and aggressive management. However, a comprehensive approach to identify biomarkers of irAE is lacking. Here, we utilize a strategy that combines pharmacovigilance data and omics data, and evaluate associations between multi-omics factors and irAE reporting odds ratio across different cancer types. We identify a bivariate regression model of LCP1 and ADPGK that can accurately predict irAE. We further validate LCP1 and ADPGK as biomarkers in an independent patient-level cohort. Our approach provides a method for identifying potential biomarkers of irAE in cancer immunotherapy using both pharmacovigilance data and multi-omics data.


Assuntos
Genômica , Imunoterapia/efeitos adversos , Neoplasias/imunologia , Neoplasias/terapia , Biomarcadores Tumorais/metabolismo , Estudos de Coortes , Análise Fatorial , Humanos , Proteínas dos Microfilamentos/metabolismo , Reprodutibilidade dos Testes
6.
Medicine (Baltimore) ; 99(40): e21503, 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33019382

RESUMO

Hepatitis B virus (HBV) infection is a leading cause of hepatocellular carcinoma (HCC), but HBV-HCC related prognosis signature remains rarely investigated. This study was to identify an integrated long non-coding RNAs-messenger RNAs (lncRNA-mRNA) signature for prediction of overall survival (OS) and explore their underlying functions.One RNA-sequencing dataset (training set, n = 95) and one microarray dataset E-TABM-36 (validation set, n = 44) were collected. Least absolute shrinkage and selection operator analysis was performed to identify an lncRNA-mRNA prognosis signature. The OS difference of patients in the high-risk and low-risk risk groups was evaluated by Kaplan-Meier curve. Area under the receiver operating characteristic curve (AUC), Harrell concordance index (C-index) calculation, and multivariate analyses with clinical characteristics were used to determine the prognostic ability. Furthermore, a coexpression network was constructed to interpret the functions.Nine signature genes (3 lncRNAs and 6 mRNAs) were selected to generate the risk score model. Patients belonging to the high-risk group showed a significantly shorter survival than those of the low-risk group. The prediction accuracy of the risk score for 5-year OS was 0.936 and 0.905 for the training set and validation set, respectively. Also, this risk score was independent of various clinical variables for the prognosis prediction. Incorporation of the risk score remarkably increased the predictive power of the routine clinical prognostic factors (vascular invasion status, tumor recurrence status) (AUC = 0.942 vs 0.628; C-index = 0.7997 vs 0.6908). Furthermore, LncRNA insulin-like growth factor 2 antisense RNA (IGF2-AS) and long intergenic non-protein coding RNA 342 (LINC00342) were predicted to exert tumor suppression effects by regulating homeobox D1 (HOXD1) and secreted frizzled related protein 5 (SFRP5), respectively; while lncRNA rhophilin Rho GTPase binding protein 1 antisense RNA 1 (RHPN1-AS1) may possess carcinogenic potential by promoting the transcription of chromobox 2 (CBX2), cell division cycle 20 (CDC20), matrix metallopeptidase 12 (MMP12), stratifin (SFN), tripartite motif containing 16 (TRIM16), and uroplakin 3A (UPK3A). These mRNAs may be associated with cell proliferation or apoptosis related pathways.This study may provide a novel, effective prognostic biomarker, and some therapeutic targets for HBV-HCC patients.


Assuntos
Carcinoma Hepatocelular/genética , Hepatite B/genética , Neoplasias Hepáticas/genética , RNA Longo não Codificante/genética , RNA Mensageiro/genética , Idoso , Biomarcadores Tumorais/genética , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/virologia , Estudos de Casos e Controles , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/virologia , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Medição de Risco
7.
Medicine (Baltimore) ; 99(40): e22203, 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33019395

RESUMO

Breast cancer (BC) is a disease of high mortality rate because of high malignant, while early diagnosis and personal management may make a better prognosis possible. This study aimed to establish and validate lncRNAs signatures to improve the prognostic prediction for BC.RNA sequencing data along with the corresponding clinical information of patients with BC were gained from The Cancer Genome Atlas (TCGA). Prognostic differentially expressed lncRNAs were obtained using differentially expressed lncRNAs analysis (P value <.01 and |fold change| > 2) and univariate cox regression (P value <.05). By applying least absolute shrinkage and selection operation (LASSO) Cox regression analysis along with 10-fold cross-validation, 2 lncRNA-based signatures were constructed in the training, test and whole set.A 14-lncRNAs signature and a 10-lncRNAs signature were built for overall survival (OS) and relapse-free survival (RFS) respectively in the 3 sets. BC patients were divided into high-risk groups and low-risk groups depended on median risk score value. Significant differences were found for OS and RFS between 2 groups in the 3 sets. The time-dependent receiver operating characteristic (ROC) curves analysis demonstrated that our lncRNAs signatures had better predictive capacities of survival and recurrence for BC patients as well as enhancing the predictive ability of the tumor node metastasis (TNM) stage system.These results indicate that the 2 lncRNAs signatures with the potential to be biomarkers to predict the prognosis of BC for OS and RFS.


Assuntos
Neoplasias da Mama/genética , Carcinoma Ductal de Mama/genética , RNA Longo não Codificante/genética , Adulto , Idoso , Biomarcadores Tumorais/genética , Neoplasias da Mama/mortalidade , Intervalo Livre de Doença , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Pessoa de Meia-Idade , Intervalo Livre de Progressão , Modelos de Riscos Proporcionais , Curva ROC
8.
Zhonghua Bing Li Xue Za Zhi ; 49(9): 886-890, 2020 Sep 08.
Artigo em Chinês | MEDLINE | ID: mdl-32892552

RESUMO

Objective: To study the proportion and clinicopathological characteristics of gastric adenocarcinoma with enteroblastic differentiation (GAED) in gastric cancers showing an elevated serum alpha fetoprotein(AFP). Methods: A total of 724 resected gastric adenocarcinomas were collected from 2008 to 2018 at the 904 Hospital of Joint Service Support Force, and cases with pre-operative serum AFP>10 µg/L were screened. From the cases with elevated serum AFP, GAED cases were further evaluated based on morphology. Then the clincopathological features and immunohistochemical phenotypes of GAED were reviewed. In addition, the amplification of HER2 gene was detected with fluorescence in situ hybridization(FISH). When overall survival (OS) and progression-free survival (PFS) of GAED were analyzed, 289 cases ordinary gastric adenocarcinoma with normal serum AFP were employed as a control. Results: The percentage of GAED was 44% (11/25) in gastric cancers with elevated serum AFP. GAED was histologically tubular or papillary with clear cytoplasm, and some GAED cases showed cystadenoid structure similar to embryo sac (5 cases), homogeneous eosinophilic granules (4 cases) and intragland ulareosinophilic material (6 cases). All 11 GAED cases had lymph node metastasis. Liver metastasis and vascular thrombus were observed in 2 cases and 5 cases respectively. GAED was immunohistochemically positive for CDX2 (11/11), CD10 (8/11) and MUC2(3/11), which were intestinal epithelium differentiation markers. Meanwhile, primitive markers SALL4 (8/11), GPC3 (7/11) and AFP (5/11) were also expressed in GAED, and HER2 gene amplification was found in 3 cases (3/11) of GAED. Lastly, the PFS of GAED were significantly shorter than that of the control group (P=0.02), while OS was not statistically different between these two groups (P=0.99). Conclusions: Patients with GAED usually have a higher rate of elevated serum AFP in gastric adenocarcinoma, and the cancer exhibites features of both intestinal and primitive differentiation. As GAED is highly invasive, the prognosis of GAED may be poor. For GAED, the diagnosis of well-differentiated or moderately-differentiated adenocarcinoma should be avoided, because this diagnosis leads to underestimated malignant potential.


Assuntos
Adenocarcinoma , Neoplasias Gástricas , Biomarcadores Tumorais , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , alfa-Fetoproteínas
9.
Zhonghua Bing Li Xue Za Zhi ; 49(9): 910-915, 2020 Sep 08.
Artigo em Chinês | MEDLINE | ID: mdl-32892556

RESUMO

Objective: To investigate the clinicopathological characteristics, immunophenotypes, and diagnostic and differential diagnostic features of myxoid solitary fibrous tumor (SFT). Methods: Seven cases of myxoid SFT were collected from the archives of Zhejiang Provincial People's Hospital from January 2014 to December 2019. The clinical features, histomorphology, immunohistochemistry, molecular genetics and prognosis were analyzed and the relevant literature was reviewed. Results: There were three male and four female patients ranging from 32 to 67 years. Locations included the pleura (three cases), pelvic cavity, vagina, parotid gland, and nasal cavity(one each). Tumor size ranged from 2.7 to 13.5 cm. Histologically, all cases were characterized predominantly by the presence of myxoid stroma comprising 55% to 90% of the tumor (mean 72%). The tumors were composed of predominantly stellated, spindled or ovoid cells disposed haphazardly, in loose fascicles, or in anastomosing strands imparting a microcystic/reticular appearance in a extensively myxoid, richly vascularized stroma. Staghorn-shaped branching vessels and thin strands of collagen were commonly seen between tumors cells amidst the myxoid background. These myxoid areas were punctuated by small cellular areas showing diagnostic features of classical SFT, which were present in all seven cases. Areas showing giant cell angifibroma-like change were noted in 2 cases and focal lipomatous metaplasia was identified in 1 case. Atypical features suggestive of aggressive behavior were present in 2 cases and in one of the cases myxoid SFT with high-grade sarcomatous overgrowth was noted. Immunohistochemically, tumor cells in all cases stained positively for STAT6 and CD34. Polymerase chain reaction technique showed in both the examined cases the characteristic NAB2ex4-STAT6ex2 fusion gene. According to the Demicco's risk assessment model, four cases were classfied as low, one was classified as moderate and 2 was classified as high. Follow-up information was obtained in 4 cases. One tumor recurred 3 times within 48 months after operation, and the other 3 cases had no tumor recurrence and metastasis. Conclusions: Myxoid SFT represents a rare morphologic variant of SFT with biological behaviors ranging from indolent to aggressive. Myxoid SFT should be included in the differential diagnostic spectrums of soft tissue tumors with significantly myxoid change. Carefully searching for the typical SFT histomorphology with the use of immunohistochemistry and if necessary, molecularly testing for NAB2-STAT6 fusion can help to distinguish myxoid SFT from its many mimickers.


Assuntos
Sarcoma , Neoplasias de Tecidos Moles , Tumores Fibrosos Solitários , Biomarcadores Tumorais , Feminino , Humanos , Imuno-Histoquímica , Masculino , Prognóstico , Fator de Transcrição STAT6
10.
Tumour Biol ; 42(9): 1010428320958603, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32964798

RESUMO

This study aimed to investigate whether changes in progastrin-releasing peptide (ProGRP) levels correlate with treatment response and can be used to optimize clinical management of patients with small-cell lung cancer. Patients with small-cell lung cancer (any stage) receiving chemotherapy were eligible. ProGRP was measured in serum/plasma at baseline and after each chemotherapy cycle using the Elecsys® ProGRP assay (Roche Diagnostics). Treatment response was assessed by computed tomography scan. The primary objective was to examine whether changes in ProGRP levels correlated with computed tomography scan results after two cycles of chemotherapy. The prognostic value of ProGRP among patients receiving first-line chemotherapy was also assessed. Overall, 261 patients from six centers were eligible. Among patients with elevated baseline ProGRP (>100 pg/mL), a ProGRP decline after Cycle 2 was associated with nonprogression (area under the curve: 84%; 95% confidence interval: 72.8-95.1; n = 141). ProGRP changes from baseline to end of Cycle 1 were predictive of response, as determined by computed tomography scan 3 weeks later (area under the curve: 87%; 95% confidence interval: 74.1-99.2; n = 137). This was enhanced by repeat measurements, with a 92% area under the curve (95% confidence interval: 85.3-97.8) among patients with ProGRP data after both Cycles 1 and 2 (n = 123); if a patient experienced a ≥25% decline in ProGRP after Cycle 1, and ProGRP remained stable or decreased after Cycle 2, the probability of finding progression on the interim computed tomography scan at the end of Cycle 2 was almost zero (sensitivity: 100%, specificity: 71%). Both ProGRP levels at baseline and at the end of first-line chemotherapy were prognostic; the latter provided a moderately improved hazard ratio of 2.43 (95% confidence interval: 1.33-4.46; n = 110) versus 1.87 (95% confidence interval: 1.04-3.37; n = 216). In summary, for patients with small-cell lung cancer and elevated baseline ProGRP levels, ProGRP may be a simple, reliable, and repeatable tool for monitoring response to chemotherapy and provide valuable prognostic information.


Assuntos
Neoplasias Pulmonares/sangue , Fragmentos de Peptídeos/sangue , Carcinoma de Pequenas Células do Pulmão/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Biomarcadores Tumorais/sangue , China , Europa (Continente) , Feminino , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Prognóstico , Proteínas Recombinantes/sangue , Sensibilidade e Especificidade , Carcinoma de Pequenas Células do Pulmão/diagnóstico por imagem , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Tomografia Computadorizada por Raios X
11.
Zhonghua Zhong Liu Za Zhi ; 42(8): 648-652, 2020 Aug 23.
Artigo em Chinês | MEDLINE | ID: mdl-32867456

RESUMO

Objective: To investigate the relationship between KDM6A mutation or expression and clinicopathological characteristics of gastric cancer. Methods: Fifty-seven cases of gastric cancer tissues were analyzed by second-generation sequencing, and bioinformation database such as Cbioportal, Kaplan Meier-Plotter, and the Human Protein Atlas were used to analyze the relationship between KDM6A mutation and clinicopathological characteristics of gastric cancer. Results: Among 57 gastric cancer samples, 14 were KDM6A mutation, and the mutation proportion was 24.6%. Compared with the non-mutation group, the Borrmann classification, T stage, TNM stage and tumor diameter of KDM6A mutant group were significantly different (all P<0.05). The median survival time of the KDM6A mutant patients was 53.5 months, significantly shorter than 72.0 months of the KDM6A non-mutation patients (P=0.007). The analysis result of Kaplan Meier-Plotter database showed that, among all of the 875 patients, 655 patients had low KDM6A expression and 220 patients had high expression. The median survival time of patients with low expression was 23.5 months, significantly shorter than 30.8 months of patients with high expression (P=0.002). In male, gastric cancer patients with stage Ⅲ, intestinal type, diffuse type, simple surgical treatment and fluorouracil chemotherapy, the expression of KDM6A is related to the patient's overall survival time (all P<0.05). The analysis result of Cbioportal database showed that, among all of the 1 172 gastric cancer patients, 70 patients with KDM6A mutation, 1100 patients with non-mutation. The median overall survival time of mutant patients was 28.9 months, significantly shorter than 35.9 months of non-mutation patients (P<0.001). The analysis result of Human Protein Atlas database showed that, among all of the 355 gastric cancer patients, 97 patients had high KDM6A expression and 258 patients had low KDM6A expression. The median survival time of patients with low expression was 13.7 months, significantly shorter than 19.8 months of patients with high expression (P=0.022). Conclusions: The survival time of gastric cancer patients with KDM6A mutation or low expression is shorter. The mutation and expression of KDM6A are related to clinical pathological factors, which may become a potential target for the diagnosis and treatment of gastric cancer.


Assuntos
Biomarcadores Tumorais/metabolismo , Regulação Neoplásica da Expressão Gênica/genética , Histona Desmetilases/metabolismo , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Histona Desmetilases/genética , Humanos , Metástase Linfática , Masculino , Mutação/genética , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Análise de Sobrevida
12.
Medicine (Baltimore) ; 99(33): e21667, 2020 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-32872031

RESUMO

BACKGROUND: This study will explore the association between tumor necrosis factor α (TNF-α) and uterine fibroids (UFs). METHODS: We will retrieve electronic databases in Cochrane Library, PUBMED, EMBASE, Web of Science, WANGFANG, Chinese Biomedical Literature Database, and China National Knowledge Infrastructure from inception to the present. All potential case-controlled studies investigating the association between TNF-α and UFs will be included in this study. Two researchers will independently select literature, appraise study quality, and extract outcome data. We will utilize a fixed-effects model or a random-effects model to synthesize outcome data. All data analysis will be performed by RevMan 5.3 software. RESULTS: The present study will supply high-quality synthesis and/or descriptive analysis of the recent evidence to explore the association between TNF-α and UFs. CONCLUSION: This study will exert evidence to determine whether or not TNF-α is associated with UFs. STUDY REGISTRATION NUMBER: INPLASY202070010.


Assuntos
Leiomioma/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Neoplasias Uterinas/metabolismo , Biomarcadores Tumorais , Estudos de Casos e Controles , Feminino , Humanos , Revisões Sistemáticas como Assunto
13.
Hua Xi Kou Qiang Yi Xue Za Zhi ; 38(4): 371-375, 2020 Aug 01.
Artigo em Chinês | MEDLINE | ID: mdl-32865353

RESUMO

OBJECTIVE: To investigate the prognostic value of plasma miR-1290 in patients with oral squamous cell carcinoma (OSCC). METHODS: Seventy patients with OSCC admitted to Danzhou People's Hospital from January 2014 to December 2018 were included in this study. Real-time fluorescence quantitative polymerase chain reaction (PCR) was used to detect the expression of miR-1290 in these patients. The optimal cut-off value of plasma miR-1290 expression was determined by the ROC curve method, and patients with OSCC were divided into the high (n=31) and low (n=39) miR-1290-expressing groups. The clinicopathological features of the two groups were compared, and survival curves were drawn using the Kaplan-Meier method. Risk factors affecting the poor prognosis of patients were analyzed using univariate and multivariate COX regression models. RESULTS: The expression level of plasma miR-1290 in the OSCC group was significantly lower than that in the control group (0.65±0.14 vs. 2.06±0.90; t=13.912, P<0.001). The low expression of plasma miR-1290 appeared to be related to the clinical stage, differentiation degree, tumor diameter, and lymph node metastasis of OSCC (P<0.05). Survival analysis showed that the overall survival rate and the progression-free survival rate of the low-miR-1290 group were significantly lower than that of the high-miR-1290 group (P<0.01). Multivariate COX regression analysis showed that clinical stage, lymph node metastasis, and plasma miR-1290<1.14 were independent risk factors for the poor prognosis of patients with OSCC (P<0.05). CONCLUSIONS: The expression level of plasma miR-1290 in patients with OSCC significantly decreased, and the low expression of miR-1290 is related to the short survival time of OSCC patients. Thus, miR-1290 may be a potential marker predicting the poor prognosis of OSCC.


Assuntos
Carcinoma de Células Escamosas , MicroRNAs , Neoplasias Bucais , Biomarcadores Tumorais , Humanos , Metástase Linfática , Prognóstico
14.
Nat Commun ; 11(1): 4383, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32873799

RESUMO

Mongolia has the highest incidence of hepatocellular carcinoma (HCC) in the world, but its causative factors and underlying tumor biology remain unknown. Here, we describe molecular characteristics of HCC from 76 Mongolian patients by whole-exome and transcriptome sequencing. We present a comprehensive analysis of mutational signatures, driver genes, and molecular subtypes of Mongolian HCC compared to 373 HCC patients of different races and ethnicities and diverse etiologies. Mongolian HCC consists of prognostic molecular subtypes similar to those found in patients from other areas of Asia, Europe, and North America, as well as other unique subtypes, suggesting the presence of distinct etiologies linked to Mongolian patients. In addition to common driver mutations (TP53, CTNNB1) frequently found in pan-cancer analysis, Mongolian HCC exhibits unique drivers (most notably GTF2IRD2B, PNRC2, and SPTA1), the latter of which is associated with hepatitis D viral infection. These results suggest the existence of new molecular mechanisms at play in Mongolian hepatocarcinogenesis.


Assuntos
Biomarcadores Tumorais/genética , Carcinoma Hepatocelular/genética , Regulação Neoplásica da Expressão Gênica , Hepatite D/genética , Neoplasias Hepáticas/genética , Idoso , Carcinogênese/genética , Carcinoma Hepatocelular/epidemiologia , Carcinoma Hepatocelular/cirurgia , Carcinoma Hepatocelular/virologia , Análise Mutacional de DNA , Feminino , Perfilação da Expressão Gênica , Hepatectomia , Hepatite D/epidemiologia , Hepatite D/cirurgia , Hepatite D/virologia , Vírus Delta da Hepatite/isolamento & purificação , Humanos , Incidência , Fígado/patologia , Fígado/cirurgia , Fígado/virologia , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/cirurgia , Neoplasias Hepáticas/virologia , Masculino , Pessoa de Meia-Idade , Mongólia/epidemiologia , Mutação , Prognóstico , Sequenciamento Completo do Exoma
15.
Nat Commun ; 11(1): 4391, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32873806

RESUMO

Deep learning with Convolutional Neural Networks has shown great promise in image-based classification and enhancement but is often unsuitable for predictive modeling using features without spatial correlations. We present a feature representation approach termed REFINED (REpresentation of Features as Images with NEighborhood Dependencies) to arrange high-dimensional vectors in a compact image form conducible for CNN-based deep learning. We consider the similarities between features to generate a concise feature map in the form of a two-dimensional image by minimizing the pairwise distance values following a Bayesian Metric Multidimensional Scaling Approach. We hypothesize that this approach enables embedded feature extraction and, integrated with CNN-based deep learning, can boost the predictive accuracy. We illustrate the superior predictive capabilities of the proposed framework as compared to state-of-the-art methodologies in drug sensitivity prediction scenarios using synthetic datasets, drug chemical descriptors as predictors from NCI60, and both transcriptomic information and drug descriptors as predictors from GDSC.


Assuntos
Antineoplásicos/farmacologia , Aprendizado Profundo , Processamento de Imagem Assistida por Computador/métodos , Neoplasias/tratamento farmacológico , Antineoplásicos/uso terapêutico , Teorema de Bayes , Biomarcadores Tumorais/genética , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Conjuntos de Dados como Assunto , Resistencia a Medicamentos Antineoplásicos , Ensaios de Seleção de Medicamentos Antitumorais/métodos , Perfilação da Expressão Gênica , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Neoplasias/patologia , Análise de Sequência com Séries de Oligonucleotídeos
16.
Tokai J Exp Clin Med ; 45(3): 148-151, 2020 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-32901905

RESUMO

PURPOSE: Pheochromocytoma (PCC) and paraganglioma (PGL) associated with the succinate dehydrogenase (SDH) germline mutations are characterized by negative results of immunohistochemistry tests for SDH subunit B (SDHB). Genetic testing for the SDH complex (SDHA, SDHB, SDHC, SDHD, and SDHAF2) is indicated only in patients with those diseases in whom immunohistochemistry tests for SDHB as a surrogate marker to detect the SDH complex mutation yield negative results. Two novel SDHB germline mutations, L157X and P236S, in PGL were previously reported. We therefore examined immunohistochemistry testing for SDHB in the PGLs with the SDHB germline mutations of L157X and P236S. METHODS: Immunohistochemistry for SDHB was performed in PGLs with the SDHB germline mutations of L157X and P236S. Five cases of sporadic PCC were subject to immunohistochemistry testing for SDHB. Normal tissue from the adrenal cortex adjacent to the sporadic PCC was used as the external positive control. RESULTS: Immunohistochemistry results were positive for SDHB in PGLs with the SDHB germline mutation of L157X and P236S, all five cases of sporadic PCC, and the adrenal cortex as the external positive control. CONCLUSION: Immunohistochemistry tests for SDHB showed positivity in PGLs associated with the SDHB germline mutations of L157X and P236S. Thus, immunohistochemistry testing for SDHB might not always reveal a surrogate marker in formal genetic testing of the SDH complex.


Assuntos
Neoplasias das Glândulas Suprarrenais/genética , Biomarcadores Tumorais/metabolismo , Mutação em Linhagem Germinativa , Paraganglioma/genética , Coloração e Rotulagem/métodos , Succinato Desidrogenase/genética , Succinato Desidrogenase/metabolismo , Córtex Suprarrenal/metabolismo , Humanos , Imuno-Histoquímica , Resultados Negativos
17.
Nat Commun ; 11(1): 4660, 2020 09 16.
Artigo em Inglês | MEDLINE | ID: mdl-32938908

RESUMO

Intratumor spatial heterogeneity facilitates therapeutic resistance in glioblastoma (GBM). Nonetheless, understanding of GBM heterogeneity is largely limited to the surgically resectable tumor core lesion while the seeds for recurrence reside in the unresectable tumor edge. In this study, stratification of GBM to core and edge demonstrates clinically relevant surgical sequelae. We establish regionally derived models of GBM edge and core that retain their spatial identity in a cell autonomous manner. Upon xenotransplantation, edge-derived cells show a higher capacity for infiltrative growth, while core cells demonstrate core lesions with greater therapy resistance. Investigation of intercellular signaling between these two tumor populations uncovers the paracrine crosstalk from tumor core that promotes malignancy and therapy resistance of edge cells. These phenotypic alterations are initiated by HDAC1 in GBM core cells which subsequently affect edge cells by secreting the soluble form of CD109 protein. Our data reveal the role of intracellular communication between regionally different populations of GBM cells in tumor recurrence.


Assuntos
Antígenos CD/metabolismo , Neoplasias Encefálicas/patologia , Glioblastoma/patologia , Histona Desacetilase 1/metabolismo , Proteínas de Neoplasias/metabolismo , Animais , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/mortalidade , Feminino , Proteínas Ligadas por GPI/metabolismo , Regulação Neoplásica da Expressão Gênica , Glioblastoma/genética , Glioblastoma/metabolismo , Glioblastoma/mortalidade , Histona Desacetilase 1/antagonistas & inibidores , Histona Desacetilase 1/genética , Histona Desacetilase 2/genética , Histona Desacetilase 2/metabolismo , Humanos , Camundongos SCID , Fenilbutiratos/farmacologia , Transdução de Sinais , Microambiente Tumoral , Ensaios Antitumorais Modelo de Xenoenxerto
18.
Zhonghua Bing Li Xue Za Zhi ; 49(10): 1036-1040, 2020 Oct 08.
Artigo em Chinês | MEDLINE | ID: mdl-32992419

RESUMO

Objective: To investigate the expression status and diagnostic value of SRY related high mobility group box 11 (SOX-11) and transcription factor E-3 (TFE3) in solid pseudopapillary tumors of pancreas (SPTPs). Methods: Thirty-eight cases of SPTPs, 36 cases of well-differentiated pancreatic neuroendocrine tumors (PanNETs) and six cases of pancreatic acinar cell carcinomas (PACCs) were collected at the Affiliated Drum Tower Hospital of Nanjing University Medical School from 2012 to 2019. The expression of SOX-11, TFE3 and ß-catenin was detected by immunohistochemistry, and the TFE3 gene status was detected by FISH in 18 cases of SPTPs. Results: Among the 38 SPTP patients, 29 were female and 9 were male, with a mean age of 50 years; among 36 PanNET patients, 32 were female and 4 were male, with a mean age of 39 years; for the six PACC patients, four were male and two were female, with a mean age of 60 years. ß-catenin was positive in all 38 SPTPs, but was negative in all 36 PanNETs and 5/6 PACCs. SOX-11 was positive in 35/38 (92.1%) of SPTPs, but was negative in all 36 PanNETs and 6 PACCs. TFE3 was positive in 36/38 (94.7%) of SPTPs, but was negative in all 36 PanNETs and 6 PACCs. Among these three tumors, the specificity and sensitivity of ß-catenin were 97.6% and 100.0%, the specificity and sensitivity of SOX-11 were 92.1% and 100.0%, the specificity and sensitivity of TFE3 were 94.7% and 100.0%, respectively. There was a significant difference of the expression status of all three markers in SPTPs compared with PanNETs and PACCs (P<0.01). The results of SOX-11 and TFE3 immunostaining showed high consistency (Kappa>0.6). No gene rearrangement (0/18) of TFE3 was found in SPTPs. Conclusion: SOX-11 and TFE3 are highly expressed in SPTPs, and their specificity in the differential diagnosis of SPTPs is better than that of ß-catenin.


Assuntos
Biomarcadores Tumorais/genética , Carcinoma de Células Acinares , Adulto , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/genética , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Pâncreas , Fatores de Transcrição SOXC/metabolismo
19.
Medicine (Baltimore) ; 99(38): e22261, 2020 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-32957376

RESUMO

Pancreatic cancer (PC) is one of the major causes of cancer mortality in developed countries. Therefore, there is an urgent need to derive biomarkers for early diagnosis of PC patients at high risk.This study was designed to identify a panel of miRNAs that might serve as biomarkers for the early diagnosis of PC.The data containing both PC and control samples were extracted from the Gene Expression Omnibus (GEO) database. EdgeR was applied to identify the differentially expressed miRNAs and genes between PC patients and healthy controls. Then a miRNA-mRNA network was constructed based on the differentially expressed miRNAs and genes. The miRNAs-based biomarker for PC was finally constructed by random forest. Finally, AUC was used to evaluate the performance of miRNAs to classify PC and control samples.A total of 33 differentially expressed miRNAs, 753 differentially expressed genes, and 8 miRNAs (hsa-mir-139, hsa-mir-31, hsa-mir-196b, hsa-mir-221, hsa-mir-203b, hsa-mir-215, hsa-mir-144, and hsa-mir-4433b) that play important roles in PC were identified. The target genes of these miRNAs were found to be mainly enriched in negative regulation of acute inflammatory response cell-substrate responses, and o-glycan processing pathways. The constructed biomarkers based on these 8 miRNAs could distinguish samples coming from PC and healthy controls.We identified a panel of eight-miRNAs that would serve as early diagnostic biomarkers for PC patients.


Assuntos
Biomarcadores Tumorais/genética , Detecção Precoce de Câncer , MicroRNAs/genética , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/genética , Perfilação da Expressão Gênica , Humanos , Prognóstico , RNA Mensageiro/genética
20.
Medicine (Baltimore) ; 99(38): e22281, 2020 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-32957383

RESUMO

The regulation of the gene-regenerating family member 1 alpha (REG Iα) played important roles in cancer cell biology. However, the correlation between its gene product serum REG Iα and cancer has not been evaluated. In this observational study, 130 hospitalized patients from the department of internal medicine in Zhongda Hospital Southeast University were included and assigned to cancer or noncancer groups. History, clinical, and laboratory data were obtained. Serum REG Iα levels and alanine aminotransferase were found significantly higher in patients with cancer (P < .001 and P < .05 respectively). Logistic regression analysis indicated that REG Iα was an independent risk factor for cancer (P < .001). The area under the curve of REG Iα was 0.764 and the optimal cut-off point of REG Iα was 46.97 ng/mL. Besides, the cancer patients with metastasis had significantly higher serum REG Iα levels than those in nonmetastasis cancer group (P < .05). In conclusion, serum REG Iα was significantly elevated in patients with cancer, and it might be a potential biomarker in predicting cancer occurrence and development.


Assuntos
Biomarcadores Tumorais/sangue , Litostatina/sangue , Neoplasias/sangue , Neoplasias/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
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