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1.
World J Surg Oncol ; 19(1): 266, 2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34479600

RESUMO

BACKGROUND: MicroRNA-140 (miR-140) is one of the most widely investigated miRNAs in cell carcinogenesis and cancer development. Despite present proposals of employing miR-140 as a candidate biomarker for cancer prognosis, its effectiveness in predicting patient survival and clinicopathological outcome is still under debate. METHODS: A systematic search for English literature using online databases was performed with pre-established criteria. Odds ratios (ORs) or hazard ratios (HRs) with 95% confidence intervals (CIs) were collected to delineate the correlation between miR-140 levels and cancer patient prognosis. RESULTS: For this meta-analysis, we selected 12 papers for analysis, involving 1386 participants. Based on our analysis, high levels of miR-140 were strongly correlated with enhanced patient overall survival (OS) (HR = 0.728, 95% CI = 0.601-0.882, P = 0.001). In addition, we also observed that elevated miR-140 levels significantly led to better OS in patients with cancers in different parts of the body like digestive system (HR = 0.675, 95% CI = 0.538-0.848, P = 0.001), digestive tract (HR = 0.709, 95% CI = 0.565-0.889, P = 0.003), and head and neck (HR = 0.603, 95% CI = 0.456-0.797, P < 0.001). Additionally, we verified that the low miR-140 levels was related to advanced TNM stage (OR = 0.420, 95% CI = 0.299-0.590, P < 0.001), worse histologic grade (OR = 0.410, 95% CI = 0.261-0.643, P < 0.001), and positive lymph node metastasis status (OR = 0.341, 95% CI = 0.144-0.807, P = 0.014). CONCLUSIONS: Taken together, our results suggest that elevated miR-140 levels can be employed as a favorable biomarker for cancer patient prognosis. This information can greatly benefit in the formation of an individualized therapeutic plan for the treatment of cancer patients.


Assuntos
MicroRNAs , Neoplasias , Biomarcadores Tumorais/genética , Humanos , Metástase Linfática , MicroRNAs/genética , Neoplasias/genética , Prognóstico , Modelos de Riscos Proporcionais
2.
Georgian Med News ; (316-317): 178-184, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34511468

RESUMO

Urothelial carcinoma represents the most common type of bladder cancer (>90%) and is the most frequent malignancy of the urinary tract. Most of the urothelial carcinomas are non-invasive at the time of diagnosis, however they are characterised with the risk of recurrence after surgical treatment. The aim of our study was to investigate the characteristics of tumor heterogeneity and markers of its progression in urothelial papillary carcinomas. Study included following groups: normal urothelial epithelium, urothelial papilloma, urothelial neoplasms with low malignant potential (PUNLM), non-invasive low grade papillary urothelial carcinomas (LGPUC) and non-invasive high grade papillary urothelial carcinomas (HGPUC). In addition, study included relapsed cases of non-invasive LGPUC and HGPUC. Nuclear features and mitotic counts was assessed using digital pathology software QuPath in standard H&E stained specimens. In addition, the presence of mitosis was detected as PHH3 labelled cells by immunohistochemistry. Proliferation was measured as Ki67 labelling index by immunohistochemistry. Tumor heterogeneity was investigated by the differential expression pattern of CK5, CK7 and CK20 by immunohistochemistry. Study results showed, that Nuclear features, as well as the number of mitosis, proliferation index and intratumoral heterogeneity significantly correlate with the presence of higher grade non-invasive urothelial lesions. In addition, it is possible to distinguish two major groups of non-invasive LGPUC and HGPUC, based on nuclear and phenotypic heterogeneity and mitotic and proliferative activity, I group which is characterised with higher intratumoral heterogeneity, higher mitotic count and higher proliferative activity, represents the high risk group of non-invasive LGPUC and HGPUC recurrence.


Assuntos
Carcinoma Papilar , Carcinoma de Células de Transição , Neoplasias da Bexiga Urinária , Biomarcadores Tumorais/genética , Carcinoma de Células de Transição/genética , Humanos , Neoplasias da Bexiga Urinária/genética , Urotélio
3.
World J Surg Oncol ; 19(1): 270, 2021 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-34503538

RESUMO

BACKGROUND: The abnormal expression of microRNA (miRNA) has been proved to be closely related to the occurrence and progression of tumors. A unique expression of multiple miRNAs has been found in different types of tumors. However, the correlation between miRNA and non-functional pituitary adenoma (NFPA) is not clear. In this study, miRNAs (miRNA-26b, miRNA-138, miRNA-206, and miRNA-let-7e) have been used as detection genes to compare the miRNA expression levels of NFPA subjects and healthy controls and to explore the expression of four different miRNAs in NFPA. METHODS: Ten untreated NFPA volunteers were served as subjects, and 10 normal subjects were selected as controls. Peripheral blood samples were collected, and four differentiated expressed miRNAs (miRNA-26b, miRNA-138, miRNA-206, and miRNA-let-7e) obtained in the early stage of the test group were detected, recorded, and archived by quantitative real-time PCR (qPCR). The difference and significance of endogenous miRNA expressions were explored through statistical analysis, hoping to find biomarkers for clinical treatment. RESULTS: The levels of miRNA-26b, miRNA-138, miRNA-206, and miRNA-let-7e in the peripheral serum of patients with NFPA were significantly lower than those in normal subjects (P < 0.05). CONCLUSION: miRNA-26b, miRNA-138, miRNA-206, and miRNA-let-7e may be involved in the occurrence and progress of NFPAs. This study aims to study the biological targets of NFPA. It starts from the study of whether miRNA, miRNA-26b, miRNA-138, miRNA-206, and miRNA-let-7e may be tumor suppressor genes in NFPA, which provides a basis for further exploration of tumor markers of pituitary adenoma.


Assuntos
Adenoma , MicroRNAs , Neoplasias Hipofisárias , Adenoma/genética , Biomarcadores , Biomarcadores Tumorais/genética , Humanos , MicroRNAs/genética , Neoplasias Hipofisárias/genética , Prognóstico
4.
World J Surg Oncol ; 19(1): 260, 2021 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-34465365

RESUMO

OBJECTIVE: The study aimed to compare the Steroid 5 alpha-reductase 3 (SRD5A3) expression levels in breast cancer (BC) and normal tissues, to investigate the prognostic value of SRD5A3 mRNA expression in BC patients and to identify the SRD5A3-related signaling pathways using bioinformatics approaches. METHODS: We evaluated the expression levels of SRD5A3 and survival data in BC patients using different bioinformatic databases. Further, Cox regression analysis was conducted to predict the independent prognostic factors for BC. Moreover, the association of SRD5A3 with clinicopathological factors was measured through LinkedOmics database. And the potential role of SRD5A3 was determined by Gene Ontology and KEGG pathway enrichment analysis. Finally, protein network of SRD5A3 was constructed and genetic alterations were analyzed. RESULTS: Bioinformatic data indicated that both mRNA and protein expression levels of SRD5A3 were higher in BC group than those in the normal group (P < 0.05). Besides, BC patients with higher SRD5A3 mRNA expression levels had a lower overall survival (all P < 0.05). Cox regression analysis further demonstrated the independent prognostic value of SRD5A3 in BC (P = 0.015). SRD5A3 mRNA expression was significantly associated with N stage (P < 0.001), age (P < 0.05), and histologic subtype (P < 0.001) but had no significant relationship with other clinical characteristics (all P > 0.05). Moreover, the functional enrichment analysis revealed that the SRD5A3 was involved in metabolism-related pathways (all P < 0.05). CONCLUSIONS: SRD5A3 was highly expressed in BC tissues and high SRD5A3 expression was related to poorer prognosis. SRD5A3 serves as an oncogene and might function as a potential biomarker for prognosis and a therapeutic target for BC.


Assuntos
Neoplasias da Mama , 3-Oxo-5-alfa-Esteroide 4-Desidrogenase/genética , Biomarcadores Tumorais/genética , Neoplasias da Mama/genética , Biologia Computacional , Feminino , Ontologia Genética , Humanos , Proteínas de Membrana/genética , Prognóstico , RNA Mensageiro/genética
5.
Anticancer Res ; 41(9): 4463-4470, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34475070

RESUMO

BACKGROUND/AIM: The treatment of advanced clear cell renal cell carcinoma (ccRCC) is based on stratification of patients according to prognosis (favorable, intermediate, and poor). The aim of the study was to improve prognostication by biomarkers involved in angiogenesis. PATIENTS AND METHODS: The study group consisted of 20 patients who underwent surgery for ccRCC. Gene expression analysis was peformed on a set of matched (primary tumor, metastasis, n=20+20) FFPE tissue samples. An additional analysis was done on expression data of 606 patients obtained from the TCGA Kidney Clear Cell Carcinoma (KIRC) database. Quantitative estimation of mRNA of selected genes (TaqMan human Angiogenesis Array, 97 genes) was performed by a real-time RT-PCR method with TaqMan® arrays. RESULTS: Using the Cox regression model, 4 genes (PDGFB, FGF4, EPHB2 and BAI1) were identified whose expression was related to progression-free interval (PFI). Further analysis using the Kaplan Meier method conclusively revealed the relationship of BAI1 expression to prognosis (both datasets). Patients with higher BAI1 expression had significantly shorter PFI and overall survival. CONCLUSION: We showed that tumor tissue BAI1 expression level is a prognostic marker in ccRCC. Therefore, this gene might be involved in a prognostic panel to improve scoring systems on which the management of metastatic ccRCC patients is based.


Assuntos
Proteínas Angiogênicas/genética , Biomarcadores Tumorais/genética , Carcinoma de Células Renais/genética , Perfilação da Expressão Gênica/métodos , Neoplasias Renais/genética , Receptores Acoplados a Proteínas G/genética , Regulação para Cima , Carcinoma de Células Renais/mortalidade , Carcinoma de Células Renais/cirurgia , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Renais/mortalidade , Neoplasias Renais/cirurgia , Masculino , Análise de Sequência com Séries de Oligonucleotídeos , Prognóstico , Análise de Regressão , Análise de Sobrevida
6.
Anticancer Res ; 41(9): 4489-4495, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34475074

RESUMO

BACKGROUND/AIM: The chemokine receptors C-X-C chemokine receptor type 4 (CXCR4) and C-C chemokine receptor type 7 (CCR7) play an important role in the invasion and metastasis of cancer. This study investigated the relationship between relative expression of CXCR4 and CCR7 mRNA, clinicopathological factors, and outcomes in patients with colorectal cancer (CRC). PATIENTS AND METHODS: We studied 202 patients who underwent surgery for CRC. The expression levels of CXCR4 and CCR7 mRNA in cancerous tissue were measured using quantitative real-time reverse-transcriptase polymerase chain reaction. RESULTS: High CCR7 mRNA expression levels in CRC tissues were positively associated with tumour size and were more frequently associated with cancer of the rectum than of the colon. Moreover, outcomes were significantly poorer in patients with high CCR7 mRNA expression than in those with low expression. On multivariate Cox regression analysis, a higher CCR7 mRNA expression level was a significant independent predictor of poorer overall survival in patients with CRC. CONCLUSION: Overexpression of CCR7 mRNA may be a useful independent prognostic factor in patients with CRC.


Assuntos
Neoplasias Colorretais/cirurgia , Perfilação da Expressão Gênica/métodos , Receptores CCR7/genética , Receptores CXCR4/genética , Regulação para Cima , Idoso , Biomarcadores Tumorais/genética , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Análise de Sobrevida , Resultado do Tratamento , Carga Tumoral
8.
Anticancer Res ; 41(9): 4295-4304, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34475049

RESUMO

BACKGROUND/AIM: Renal cell carcinoma (RCC) is the most common type of kidney cancer in adults. The aim of this study was to elucidate the molecular pathogenesis of sporadic RCC in Taiwan. MATERIALS AND METHODS: Fifteen patients with RCC were screened for mutations in the von Hippel-Lindau (VHL) gene by PCR and Sanger sequencing. The methylation status of promoters of 24 tumor suppressor genes by methylation sensitive multiplex ligation-dependent probe amplification analysis was also determined. RESULTS: Inactivation of the VHL gene was observed in 5 cases: three missense somatic mutations, one promoter methylation, and one small deletion. In RCCs, methylation was most frequently observed in APC (100%), CDKN2B (92.9%), CASP8, MLH1_167, and KLLN (85.7.4%), but not in FHIT, MLH1_463, DAPK1, or HIC1 (0%). CONCLUSION: In addition to VHL inactivation, promoter methylation of APC may be a universal pathognomonic event in the tumorigenesis of RCC and a candidate diagnostic and therapeutic biomarker.


Assuntos
Proteína da Polipose Adenomatosa do Colo/genética , Carcinoma de Células Renais/diagnóstico , Metilação de DNA , Neoplasias Renais/diagnóstico , Proteína Supressora de Tumor Von Hippel-Lindau/genética , Biomarcadores Tumorais/genética , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/patologia , Detecção Precoce de Câncer , Epigênese Genética , Feminino , Humanos , Neoplasias Renais/genética , Neoplasias Renais/patologia , Masculino , Mutação de Sentido Incorreto , Estadiamento de Neoplasias , Regiões Promotoras Genéticas , Análise de Sequência de DNA , Deleção de Sequência
9.
J Coll Physicians Surg Pak ; 31(9): 1051-1056, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34500520

RESUMO

OBJECTIVE: To investigate the expression of chromobox 2 (CBX2) in colorectal adenoma (CRA) and colorectal cancer (CRC), and analyse its correlation with various clinicopathological parameters. STUDY DESIGN: Observational study. PLACE AND DURATION OF STUDY: Pathology Department, Huashan Hospital, Fudan University, from December 2019 to December 2020. METHODOLOGY: The mRNA level of CBX2 in colorectal mucosa, CRA and CRC was evaluated in gene expression profiling interactive analysis (GEPIA) and gene expression omnibus (GEO) dataset, then verified by quantitative real-time PCR (qRT-PCR). CBX2 expression by immunohistochemistry was determined in 122 samples, then its correlation was analysed with various clinicopathological parameters. Diagnostic value of CBX2 was estimated by the receiver operating characteristic curve (ROC). Prognostic value of CBX2 mRNA expression was evaluated via the Kaplan-Meier method in GEPIA. RESULTS: CBX2 expression rate in CRC (89.8%) was greater than adenoma (37.74%) and mucosa (20%). CBX2 protein levels were highest in adenocarcinoma and lowest in mucosa with intermediate level in adenoma. The area under curve (AUC) of CBX2 was 0.810 and 0.734, respectively, in distinguishing CRA from mucosa and CRC from CRA. CBX2 hyperexpression was not significantly correlated with clinicopathological variables, either in CRA or CRC. Kaplan-Meier survival analysis revealed that CBX2 mRNA hyperexpression was not associated with overall survival (OS) of CRC. Although the disease-free survival (DFS) of high CBX2 patients was shorter than those with low expression, but no obvious significance was found in colon adenocarcinoma (COAD, p=0.052) and rectal adenocarcinoma (READ, p=0.097). CONCLUSION: CBX2 expression progressively increased in the sequence of mucosa-adenoma-carcinoma, which may be used as a diagnostic biomarker and therapeutic target for CRA and CRC. Key Words: CBX2, Colorectal adenoma, Colorectal cancer, Biomarker.


Assuntos
Adenocarcinoma , Adenoma , Carcinoma , Neoplasias Colorretais , Adenocarcinoma/genética , Adenoma/genética , Biomarcadores Tumorais/genética , Neoplasias Colorretais/genética , Humanos , Membrana Mucosa , Complexo Repressor Polycomb 1 , Prognóstico
10.
Int J Mol Sci ; 22(16)2021 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-34445467

RESUMO

Ribosome-binding protein 1 (RRBP1) is a potential oncogene in several cancer types. However, the correlation between RRBP1 expression and the prognosis of patients with upper tract urothelial carcinoma (UTUC) remains unclear. In this study, we identified that RRBP1 is associated with carcinogenesis and metastasis in UTUC using a methylation profiling microarray. High correlations between RRBP1 and cancer stages, nodal metastasis status, molecular subtypes, and prognosis in bladder urothelial cancer (BLCA) were found. Aberrant DNA methylation in the gene body region of RRBP1 was determined in UTUC tissues by methylation-specific PCR. RRBP1 expression was significantly increased in UTUC tissues and cell lines, as determined by real-time PCR and immunohistochemistry. RRBP1 depletion significantly reduced BFTC909 cell growth induced by specific shRNA. On the other hand, molecular subtype analysis showed that the expression of RRBP1 was associated with genes related to cell proliferation, epithelial-mesenchymal transition, and basal markers. A patient-derived organoid model was established to analyze patients' responses to different drugs. The expression of RRBP1 was related to chemoresistance. Taken together, these results provide the first evidence that RRBP1 gene body hypomethylation predicts RRBP1 high expression in UTUC. The data highlight the importance of RRBP1 in UTUC malignancy and chemotherapeutic tolerance.


Assuntos
Biomarcadores Tumorais/metabolismo , Proteínas de Transporte/metabolismo , Metilação de DNA , Resistencia a Medicamentos Antineoplásicos , Regulação Neoplásica da Expressão Gênica , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/patologia , Animais , Apoptose , Biomarcadores Tumorais/genética , Proteínas de Transporte/genética , Proliferação de Células , Perfilação da Expressão Gênica , Humanos , Camundongos , Prognóstico , Taxa de Sobrevida , Células Tumorais Cultivadas , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
11.
Int J Mol Sci ; 22(16)2021 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-34445479

RESUMO

A spaceflight to the International Space Station (ISS) is a dream of many researchers. We had the chance to investigate the effect of real microgravity (CellBox-2 Space mission) on the transcriptome and proteome of FTC-133 human follicular thyroid cancer cells (TCC). The cells had been sent to the ISS by a Falcon 9 rocket of SpaceX CRS-13 from Cape Canaveral (United States) and cultured in six automated hardware units on the ISS before they were fixed and returned to Earth. Multicellular spheroids (MCS) were detectable in all spaceflight hardware units. The VCL, PXN, ITGB1, RELA, ERK1 and ERK2 mRNA levels were significantly downregulated after 5 days in space in adherently growing cells (AD) and MCS compared with ground controls (1g), whereas the MIK67 and SRC mRNA levels were both suppressed in MCS. By contrast, the ICAM1, COL1A1 and IL6 mRNA levels were significantly upregulated in AD cells compared with 1g and MCS. The protein secretion measured by multianalyte profiling technology and enzyme-linked immunosorbent assay (AngiogenesisMAP®, extracellular matrix proteins) was not significantly altered, with the exception of elevated angiopoietin 2. TCC in space formed MCS, and the response to microgravity was mainly anti-proliferative. We identified ERK/RELA as a major microgravity regulatory pathway.


Assuntos
Adenocarcinoma Folicular/patologia , Biomarcadores Tumorais/metabolismo , Proteoma/metabolismo , Esferoides Celulares/patologia , Neoplasias da Glândula Tireoide/patologia , Transcriptoma , Ausência de Peso , Adenocarcinoma Folicular/genética , Adenocarcinoma Folicular/metabolismo , Biomarcadores Tumorais/genética , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Humanos , Proteoma/análise , Voo Espacial , Esferoides Celulares/metabolismo , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/metabolismo , Células Tumorais Cultivadas
12.
Int J Mol Sci ; 22(16)2021 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-34445498

RESUMO

Aberrant alternative splicing (AS) is increasingly linked to cancer; however, how AS contributes to cancer development still remains largely unknown. AS events (ASEs) are largely regulated by RNA-binding proteins (RBPs) whose ability can be modulated by a variety of genetic and epigenetic mechanisms. In this study, we used a computational framework to investigate the roles of transcription factors (TFs) on regulating RBP-AS interactions. A total of 6519 TF-RBP-AS triplets were identified, including 290 TFs, 175 RBPs, and 16 ASEs from TCGA-KIRC RNA sequencing data. TF function categories were defined according to correlation changes between RBP expression and their targeted ASEs. The results suggested that most TFs affected multiple targets, and six different classes of TF-mediated transcriptional dysregulations were identified. Then, regulatory networks were constructed for TF-RBP-AS triplets. Further pathway-enrichment analysis showed that these TFs and RBPs involved in triplets were enriched in a variety of pathways that were associated with cancer development and progression. Survival analysis showed that some triplets were highly associated with survival rates. These findings demonstrated that the integration of TFs into alternative splicing regulatory networks can help us in understanding the roles of alternative splicing in cancer.


Assuntos
Processamento Alternativo , Biologia Computacional/métodos , Neoplasias Renais/genética , Proteínas de Ligação a RNA/metabolismo , Fatores de Transcrição/metabolismo , Biomarcadores Tumorais/genética , Estudos de Casos e Controles , Bases de Dados Genéticas , Progressão da Doença , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Redes Reguladoras de Genes , Humanos , Neoplasias Renais/metabolismo , Prognóstico , Mapas de Interação de Proteínas , Análise de Sequência de RNA , Análise de Sobrevida
13.
Int J Mol Sci ; 22(16)2021 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-34445499

RESUMO

Xenoestrogens and phytoestrogens are referred to as "foreign estrogens" that are produced outside of the human body and have been shown to exert estrogen-like activity. Xenoestrogens are synthetic industrial chemicals, whereas phytoestrogens are chemicals present in the plant. Considering that these environmental estrogen mimics potentially promote hormone-related cancers, an understanding of how they interact with estrogenic pathways in human cells is crucial to resolve their possible impacts in cancer. Here, we conducted an extensive literature evaluation on the origins of these chemicals, emerging research techniques, updated molecular mechanisms, and ongoing clinical studies of estrogen mimics in human cancers. In this review, we describe new applications of patient-derived xenograft (PDX) models and single-cell RNA sequencing (scRNA-seq) techniques in shaping the current knowledge. At the molecular and cellular levels, we provide comprehensive and up-to-date insights into the mechanism of xenoestrogens and phytoestrogens in modulating the hallmarks of cancer. At the systemic level, we bring the emerging concept of window of susceptibility (WOS) into focus. WOS is the critical timing during the female lifespan that includes the prenatal, pubertal, pregnancy, and menopausal transition periods, during which the mammary glands are more sensitive to environmental exposures. Lastly, we reviewed 18 clinical trials on the application of phytoestrogens in the prevention or treatment of different cancers, conducted from 2002 to the present, and provide evidence-based perspectives on the clinical applications of phytoestrogens in cancers. Further research with carefully thought-through concepts and advanced methods on environmental estrogens will help to improve understanding for the identification of environmental influences, as well as provide novel mechanisms to guide the development of prevention and therapeutic approaches for human cancers.


Assuntos
Neoplasias/tratamento farmacológico , Neoplasias/prevenção & controle , Fitoestrógenos/uso terapêutico , Análise de Célula Única/métodos , Animais , Biomarcadores Tumorais/genética , Ensaios Clínicos como Assunto , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Masculino , Neoplasias/genética , Fitoestrógenos/farmacologia , Análise de Sequência de RNA , Ensaios Antitumorais Modelo de Xenoenxerto
14.
Int J Mol Sci ; 22(16)2021 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-34445551

RESUMO

Cancer-specific isoenzyme of phosphofructokinase II (PFKFB4), as our previous research has shown, may be one of the most important enzymes contributing to the intensification of glycolysis in hypoxic malignant melanoma cells. Although the PFKFB4 gene seems to play a crucial role in the progression of melanoma, so far there are no complete data on the expression of PFKFB4 at the isoform level and the influence of hypoxia on alternative splicing. Using RT-qPCR and semi-quantitative RT-PCR, we presented the PFKFB4 gene expression profile at the level of six isoforms described in the OMIM NCBI database in normoxic and hypoxic melanoma cells. Additionally, using VMD software, we analyzed the structure of isoforms at the protein level, concluding about the catalytic activity of individual isoforms. Our research has shown that five isoforms of PFKFB4 are expressed in melanoma cells, of which the D and F isoforms are highly constitutive, while the canonical B isoform seems to be the main isoform induced in hypoxia. Our results also indicate that the expression profile at the level of the PFKFB4 gene does not reflect the expression at the level of individual isoforms. Our work clearly indicates that the PFKFB4 gene expression profile should be definitely analyzed at the level of individual isoforms. Moreover, the analysis at the protein level allowed the selection of those isoforms whose functional validation should be performed to fully understand the importance of PFKFB4 expression in the metabolic adaptation of malignant melanoma cells.


Assuntos
Processamento Alternativo , Biomarcadores Tumorais/metabolismo , Regulação Neoplásica da Expressão Gênica , Hipóxia/fisiopatologia , Melanoma/patologia , Oxigênio/metabolismo , Fosfofrutoquinase-2/genética , Biomarcadores Tumorais/genética , Glicólise , Humanos , Melanoma/genética , Melanoma/metabolismo , Células Tumorais Cultivadas
15.
Int J Mol Sci ; 22(16)2021 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-34445557

RESUMO

Renal cell carcinomas (RCC) account for 2-3% of the global cancer burden and are characterized by the highest mortality rate among all genitourinary cancers. However, excluding conventional imagining approaches, there are no reliable diagnostic and prognostic tools available for clinical use at present. Liquid biopsies, such as urine, serum, and plasma, contain a significant amount of tumor-derived nucleic acids, which may serve as non-invasive biomarkers that are particularly useful for early cancer detection, follow-up, and personalization of treatment. Changes in epigenetic phenomena, such as DNA methylation level, expression of microRNAs (miRNAs), and long noncoding RNAs (lncRNAs), are observed early during cancer development and are easily detectable in biofluids when morphological changes are still undetermined by conventional diagnostic tools. Here, we reviewed recent advances made in the development of liquid biopsy-derived DNA methylation-, miRNAs- and lncRNAs-based biomarkers for RCC, with an emphasis on the performance characteristics. In the last two decades, a mass of circulating epigenetic biomarkers of RCC were suggested, however, most of the studies done thus far analyzed biomarkers selected from the literature, used relatively miniature, local, and heterogeneous cohorts, and suffered from a lack of sufficient validations. In summary, for improved translation into the clinical setting, there is considerable demand for the validation of the existing pool of RCC biomarkers and the discovery of novel ones with better performance and clinical utility.


Assuntos
Biomarcadores Tumorais/genética , Carcinoma de Células Renais/diagnóstico , Epigênese Genética , Neoplasias Renais/diagnóstico , Carcinoma de Células Renais/genética , Humanos , Neoplasias Renais/genética , Biópsia Líquida
16.
Int J Mol Sci ; 22(15)2021 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-34361002

RESUMO

Platelets are involved in tumor angiogenesis and cancer progression. Previous studies indicated that cancer could affect platelet content. In the current study, we investigated whether cancer-associated proteins can be discerned in the platelets of cancer patients, and whether antitumor treatment may affect the platelet proteome. Platelets were isolated from nine patients with different cancer types and ten healthy volunteers. From three patients, platelets were isolated before and after the start of antitumor treatment. Mass spectrometry-based proteomics of gel-fractionated platelet proteins were used to compare patients versus controls and before and after treatment initiation. A total of 4059 proteins were detected, of which 50 were significantly more abundant in patients, and 36 more in healthy volunteers. Eight of these proteins overlapped with our previous cancer platelet proteomics study. From these data, we selected potential biomarkers of cancer including six upregulated proteins (RNF213, CTSG, PGLYRP1, RPL8, S100A8, S100A9) and two downregulated proteins (GPX1, TNS1). Antitumor treatment resulted in increased levels of 432 proteins and decreased levels of 189 proteins. In conclusion, the platelet proteome may be affected in cancer patients and platelets are a potential source of cancer biomarkers. In addition, we found in a small group of patients that anticancer treatment significantly changes the platelet proteome.


Assuntos
Plaquetas/metabolismo , Neoplasias do Sistema Digestório/sangue , Proteoma/metabolismo , Idoso , Antineoplásicos/uso terapêutico , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Neoplasias do Sistema Digestório/tratamento farmacológico , Neoplasias do Sistema Digestório/genética , Neoplasias do Sistema Digestório/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Proteoma/genética
17.
Medicine (Baltimore) ; 100(33): e26896, 2021 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-34414945

RESUMO

PURPOSE: Obesity strongly affects the prognosis of various malignancies, including breast cancer. Leptin (LEP) may be associated with obesity and breast cancer prognosis. The purpose of our study was to determine the prognostic value of LEP in breast cancer. METHOD: We conducted a multi-omic analysis to determine the prognostic role of LEP. Different public bioinformatics platforms (Oncomine, Gene Expression Profiling Interactive Analysis, University of California Santa Cruz Xena, bc-GenExMiner, PrognoScan database, R2-Kaplan-Meier Scanner, UALCAN, Search Tool for the Retrieval of Interacting Genes/Proteins database , and The Database for Annotation, Visualization and Integrated Discovery) were used to evaluate the roles of LEP. Clinicopathological variables were evaluated. RESULTS: LEP was downregulated in breast cancer tissues compared to levels in normal tissues. By co-expressed gene analysis, a positive correlation between LEP and SLC19A3 was observed. Based on the clinicopathological analysis, low LEP expression was associated with older age, higher stage, lymph node status, human epidermal growth factor receptor 2 (HER2) status, estrogen receptor (ER+) positivity, and progesterone receptor (PR+) positivity. Kaplan-Meier survival analysis showed that low LEP expression indicated a poorer prognosis. LEP is hypermethylated in breast cancer tissues in PrognoScan and R2-Kaplan Meier Scanner, and low LEP expression was correlated with poor prognosis. LEP protein-protein interactions were analyzed using Search Tool for the Retrieval of Interacting Genes/Proteins database. Gene ontology analysis results showed that cellular component is mainly associated with the endosome lumen, cytosol, and secretory granules and is upregulated. For the biological process energy reserve, metabolic processes exhibited the greatest regulation compared to the others. In molecular function, it was mainly enriched in a variety of combinations, but hormone activity showed the highest regulation. CONCLUSION: Our study provides evidence for the prognostic role of LEP in breast cancer and as a novel potential therapeutic target in such malignancies. Nevertheless, further validation is required.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias da Mama/genética , Regulação Neoplásica da Expressão Gênica , Leptina/genética , Neoplasias da Mama/mortalidade , Correlação de Dados , Feminino , Humanos , Pessoa de Meia-Idade , Prognóstico , Taxa de Sobrevida
19.
Int J Mol Sci ; 22(16)2021 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-34445424

RESUMO

Biomarkers for predicting individual response to radiation and for dose verification are needed to improve radiotherapy. A biomarker should optimally show signal fidelity, meaning that its level is stable and proportional to the absorbed dose. miRNA levels in human blood serum were suggested as promising biomarkers. The aim of the present investigation was to test the miRNA biomarker in leukocytes of breast cancer patients undergoing external beam radiotherapy. Leukocytes were isolated from blood samples collected prior to exposure (control); on the day when a total dose of 2 Gy, 10 Gy, or 20 Gy was reached; and one month after therapy ended (46-50 Gy in total). RNA sequencing was performed and univariate analysis was used to analyse the effect of the radiation dose on the expression of single miRNAs. To check if combinations of miRNAs can predict absorbed dose, a multinomial logistic regression model was built using a training set from eight patients (representing 40 samples) and a validation set with samples from the remaining eight patients (15 samples). Finally, Broadside, an explorative interaction mining tool, was used to extract sets of interacting miRNAs. The most prominently increased miRNA was miR-744-5p, followed by miR-4461, miR-34a-5p, miR-6513-5p, miR-1246, and miR-454-3p. Decreased miRNAs were miR-3065-3p, miR-103a-2-5p, miR-30b-3p, and miR-5690. Generally, most miRNAs showed a relatively strong inter-individual variability and different temporal patterns over the course of radiotherapy. In conclusion, miR-744-5p shows promise as a stable miRNA marker, but most tested miRNAs displayed individual signal variability which, at least in this setting, may exclude them as sensitive biomarkers of radiation response.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias da Mama/radioterapia , Perfilação da Expressão Gênica/métodos , Regulação Neoplásica da Expressão Gênica/efeitos da radiação , MicroRNAs/genética , Idoso , Biomarcadores Tumorais/sangue , Neoplasias da Mama/sangue , Neoplasias da Mama/genética , Fracionamento da Dose de Radiação , Feminino , Humanos , Pessoa de Meia-Idade , Análise de Sequência de RNA , Resultado do Tratamento , Regulação para Cima
20.
Int J Mol Sci ; 22(16)2021 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-34445631

RESUMO

To better understand the etiology of inflammatory breast cancer (IBC) and identify potential therapies, we studied genomic alterations in IBC patients. Targeted, next-generation sequencing (NGS) was performed on cell-free DNA (cfDNA) (n = 33) and paired DNA from tumor tissues (n = 29) from 32 IBC patients. We confirmed complementarity between cfDNA and tumor tissue genetic profiles. We found a high incidence of germline variants in IBC patients that could be associated with an increased risk of developing the disease. Furthermore, 31% of IBC patients showed deficiencies in the homologous recombination repair (HRR) pathway (BRCA1, BRCA2, PALB2, RAD51C, ATM, BARD1) making them sensitive to poly (ADP-ribose) polymerase (PARP) inhibitors. We also characterized the tumor-infiltrating lymphocytes (TILs) in tumor tissue biopsies by studying several markers (CD4, CD8, FoxP3, CD20, PD-1, and PD-L1) through immunohistochemistry (IHC) staining. In 7 of 24 (29%) patients, tumor biopsies were positive for PD-L1 and PD-1 expression on TILs, making them sensitive to PD-1/PD-L1 blocking therapies. Our results provide a rationale for considering PARP inhibitors and PD-1/PDL1 blocking immunotherapy in qualifying IBC patients.


Assuntos
Biomarcadores Tumorais/genética , Ácidos Nucleicos Livres/genética , Neoplasias Inflamatórias Mamárias/patologia , Linfócitos do Interstício Tumoral/imunologia , Terapia de Alvo Molecular , Mutação , Microambiente Tumoral/imunologia , Adulto , Idoso , Antígeno B7-H1/genética , Antígeno B7-H1/metabolismo , Ácidos Nucleicos Livres/análise , Feminino , Seguimentos , Regulação Neoplásica da Expressão Gênica , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Neoplasias Inflamatórias Mamárias/genética , Neoplasias Inflamatórias Mamárias/imunologia , Pessoa de Meia-Idade , Prognóstico , Receptor ErbB-2/metabolismo , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Estudos Retrospectivos , Taxa de Sobrevida
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