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1.
Int J Mol Sci ; 22(5)2021 Mar 06.
Artículo en Inglés | MEDLINE | ID: mdl-33800786

RESUMEN

Pancreatic ductal adenocarcinoma (PDAC) is known as a highly aggressive malignant disease. Prognosis for patients is notoriously poor, despite improvements in surgical techniques and new (neo)adjuvant chemotherapy regimens. Early detection of PDAC may increase the overall survival. It is furthermore foreseen that precision medicine will provide improved prognostic stratification and prediction of therapeutic response. In this review, omics-based discovery efforts are presented that aim for novel diagnostic and prognostic biomarkers of PDAC. For this purpose, we systematically evaluated the literature published between 1999 and 2020 with a focus on protein- and protein-glycosylation biomarkers in pancreatic cancer patients. Besides genomic and transcriptomic approaches, mass spectrometry (MS)-based proteomics and glycomics of blood- and tissue-derived samples from PDAC patients have yielded new candidates with biomarker potential. However, for reasons discussed in this review, the validation and clinical translation of these candidate markers has not been successful. Consequently, there has been a change of mindset from initial efforts to identify new unimarkers into the current hypothesis that a combination of biomarkers better suits a diagnostic or prognostic panel. With continuing development of current research methods and available techniques combined with careful study designs, new biomarkers could contribute to improved detection, prognosis, and prediction of pancreatic cancer.


Asunto(s)
Biomarcadores de Tumor/análisis , Carcinoma Ductal Pancreático/diagnóstico , Glicómica/métodos , Glicoproteínas/análisis , Espectrometría de Masas/métodos , Proteínas de Neoplasias/análisis , Neoplasias Pancreáticas/diagnóstico , Proteómica/métodos , Líquidos Corporales/química , Carcinoma Ductal Pancreático/química , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/mortalidad , Toma de Decisiones Clínicas , Diagnóstico Diferencial , Detección Precoz del Cáncer , Humanos , Síndromes Neoplásicos Hereditarios/diagnóstico , Síndromes Neoplásicos Hereditarios/epidemiología , Síndromes Neoplásicos Hereditarios/genética , Neoplasias Pancreáticas/química , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/mortalidad , Pancreatitis Crónica/diagnóstico , Lesiones Precancerosas/diagnóstico , Medicina de Precisión , Valor Predictivo de las Pruebas , Pronóstico , Reproducibilidad de los Resultados , Factores de Riesgo
2.
Int J Mol Sci ; 22(5)2021 Mar 06.
Artículo en Inglés | MEDLINE | ID: mdl-33800799

RESUMEN

Liquid biopsies constitute a minimally invasive means of managing cancer patients, entailing early diagnosis, follow-up and prediction of response to therapy. Their use in the germ cell tumor field is invaluable since diagnostic tissue biopsies (which are invasive) are often not performed, and therefore only a presumptive diagnosis can be made, confirmed upon examination of the surgical specimen. Herein, we provide an overall review of the current liquid biopsy-based biomarkers of this disease, including the classical, routinely used serum tumor markers-the promising microRNAs rapidly approaching the introduction into clinical practice-but also cell-free DNA markers (including DNA methylation) and circulating tumor cells. Finally, and importantly, we also explore novel strategies and challenges for liquid biopsy markers and methodologies, providing a critical view of the future directions for liquid biopsy tests in this field, highlighting gaps and unanswered questions.


Asunto(s)
Biopsia Líquida , Neoplasias de Células Germinales y Embrionarias/diagnóstico , Biomarcadores de Tumor/análisis , Biomarcadores de Tumor/sangre , Vías Clínicas , ADN de Neoplasias/química , Manejo de la Enfermedad , Femenino , Humanos , Masculino , MicroARNs/análisis , Proteínas de Neoplasias/análisis , Neoplasias de Células Germinales y Embrionarias/sangre , Neoplasias de Células Germinales y Embrionarias/química , Neoplasias de Células Germinales y Embrionarias/patología , Células Neoplásicas Circulantes , Neoplasias Ováricas/sangre , Neoplasias Ováricas/química , Neoplasias Ováricas/diagnóstico , Neoplasias Ováricas/patología , ARN Neoplásico/análisis , Neoplasias Testiculares/sangre , Neoplasias Testiculares/química , Neoplasias Testiculares/diagnóstico , Neoplasias Testiculares/patología
3.
Anticancer Res ; 41(4): 2053-2058, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33813413

RESUMEN

AIM: To investigate potential associations between selected oncomarkers [carcinoembryonic antigen (CEA), C-terminus of cytokeratin 19 (CYFRA 21-1, CYFRA), and squamous cell carcinoma antigen (SCC)] and outcomes in patients with NSCLC treated with bevacizumab plus chemotherapy. PATIENTS AND METHODS: We retrospectively analysed 105 patients with NSCLC from the Czech TULUNG registry treated at University Hospital in Pilsen with bevacizumab plus chemotherapy. Response to therapy was tested by Fisher's exact test. Survival statistics were evaluated using the Kaplan-Meier method and Cox analysis. RESULTS: Only normal values of CYFRA (not CEA or SCC) were associated with significantly better overall and progression-free survival in univariate analysis. We also observed a trend for a better disease control rate in patients with normal levels of CYFRA. In a multivariate Cox model, only CYFRA was associated with significantly better overall but not progression-free survival. CONCLUSION: In our retrospective study, we point out the possibility of using CYFRA as a prognostic marker in patients with NSCLC treated with chemotherapy plus bevacizumab.


Asunto(s)
Antígenos de Neoplasias/fisiología , Antineoplásicos/uso terapéutico , Bevacizumab/administración & dosificación , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Queratina-19/fisiología , Neoplasias Pulmonares/tratamiento farmacológico , Anciano , Antígenos de Neoplasias/análisis , Antígenos de Neoplasias/sangre , Bevacizumab/efectos adversos , Biomarcadores Farmacológicos/análisis , Biomarcadores de Tumor/análisis , Biomarcadores de Tumor/fisiología , Antígeno Carcinoembrionario/análisis , Antígeno Carcinoembrionario/sangre , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/patología , Progresión de la Enfermedad , Femenino , Humanos , Queratina-19/análisis , Queratina-19/sangre , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Valor Predictivo de las Pruebas , Pronóstico , Estudios Retrospectivos , Serpinas/análisis , Serpinas/sangre , Resultado del Tratamiento
4.
Medicine (Baltimore) ; 100(16): e25452, 2021 Apr 23.
Artículo en Inglés | MEDLINE | ID: mdl-33879677

RESUMEN

BACKGROUND: Currently, an increasing number of long noncoding RNAs (LncRNAs) have been reported to be abnormally expressed in human carcinomas and play a vital role in tumourigenesis. Some studies have been carried out to investigate the influence of the expression of LncRNA human urothelial carcinoma associated 1 (UCA1) on prognosis and clinical significance in patients with esophageal cancer, but the results are contradictory and uncertain. A meta-analysis and was conducted with controversial data to accurately assess the issue. We collected relevant TCGA data to further testify the result. In addition, bioinformatics analysis was conducted to investigate the mechanism and related pathways of LncRNA UCA1 in esophageal carcinoma. METHODS: Wanfang, Chinese Biomedical Literature Database, Chinese National Knowledge Infrastructure, the Chongqing VIP Chinese Science and Technology Periodical Database, PubMed, Embase, and Web of Science were thoroughly searched for relevant information. Two reviewers independently performed data extraction and literature quality evaluation. Odd ratio and its 95% confidence intervals were applied to evaluate the relationship between LncRNA UCA1 and clinicopathological characteristics of esophageal carcinoma patients. Hazard ratios and its 95% confidence intervals were adopted to assess the prognostic effects of LncRNA UCA1 on overall survival and disease-free survival. Meta-analysis was performed with Stata 14.0 software. To further assess the function of LncRNA UCA1 in esophageal carcinoma, relevant data from The Cancer Genome Atlas (TCGA) database was collected. Three databases, miRWalk, TargetScan, and miRDB, were used for prediction of target genes. Genes present in these 3 databases were considered as predicted target genes of LncRNA UCA1. Venny 2.1 were used for intersection analysis. Subsequently, GO, KEGG, and PPI network analysis were conducted based on the overlapping target genes of LncRNA UCA1 to explore the possible molecular mechanism in esophageal carcinoma. RESULTS: This study provides a high-quality medical evidence for the correlation between LncRNA UCA1 expression and overall survival, and between disease-free survival and clinicopathological features. Based on bioinformatics analysis, this study enhanced the understanding of the mechanism and related pathways of LncRNA UCA1 in esophageal carcinoma. CONCLUSION: The study provides updated evidence to evaluate whether the expression of LncRNA UCA1 is in association with poor prognosis in patients with esophageal carcinoma. ETHICS AND DISSEMINATION: The private information from individuals will not be published. This systematic review also should not damage participants' rights. Ethical approval is not available. The results may be published in a peer-reviewed journal or disseminated in relevant conferences. OSF REGISTRATION NUMBER: DOI 10.17605/OSF.IO/8MCHW.


Asunto(s)
Biomarcadores de Tumor/metabolismo , Carcinoma/mortalidad , Neoplasias Esofágicas/mortalidad , ARN Largo no Codificante/metabolismo , Biomarcadores de Tumor/análisis , Carcinoma/genética , Carcinoma/patología , Biología Computacional , Supervivencia sin Enfermedad , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/patología , Esófago/patología , Regulación Neoplásica de la Expresión Génica , Humanos , Metaanálisis como Asunto , Pronóstico , Mapeo de Interacción de Proteínas , Mapas de Interacción de Proteínas/genética , ARN Largo no Codificante/análisis , Revisiones Sistemáticas como Asunto
5.
Medicine (Baltimore) ; 100(16): e25507, 2021 Apr 23.
Artículo en Inglés | MEDLINE | ID: mdl-33879685

RESUMEN

BACKGROUND: Long noncoding RNA (lncRNA) is reported to be upregulated in many tumors. Although the expression of lncRNA in oral squamous cell carcinoma has been assessed, the association between lncRNA expression and prognosis or clinicopathological feature still remains controversial. Therefore, we conducted a meta-analysis to verify whether lncRNA expression was related to prognosis or clinicopathological features in patients with oral squamous cell carcinoma. METHODS: We searched Embase, PubMed, Web of Science, Cochrane library, Chinese National Knowledge Infrastructure, and Wanfang databases from inception to February 2021. The language included Chinese and English. The published literature on lncRNA expression and prognosis or clinicopathological characteristics of patients with oral squamous cell carcinoma was statistically analyzed. The combination of hazard ratios (HRs), odds ratios (OR), and 95% confidence intervals (95% CIs) were applied to evaluate the effects of lncRNA on the prognosis and clinicopathological features of oral squamous cell carcinoma. RESULTS: This study could provide a comprehensive review of the available evidence of lncRNA on the prognosis and clinicopathological features of oral squamous cell carcinoma. CONCLUSION: The conclusion of our study will provide the updated evidence to judge the lncRNA on the prognosis and clinicopathological features of oral squamous cell carcinoma.


Asunto(s)
Biomarcadores de Tumor/metabolismo , Neoplasias de la Boca/mortalidad , ARN Largo no Codificante/metabolismo , Carcinoma de Células Escamosas de Cabeza y Cuello/mortalidad , Biomarcadores de Tumor/análisis , Regulación Neoplásica de la Expresión Génica , Humanos , Metaanálisis como Asunto , Mucosa Bucal/patología , Neoplasias de la Boca/diagnóstico , Neoplasias de la Boca/genética , Neoplasias de la Boca/terapia , Estadificación de Neoplasias , Pronóstico , ARN Largo no Codificante/análisis , Carcinoma de Células Escamosas de Cabeza y Cuello/diagnóstico , Carcinoma de Células Escamosas de Cabeza y Cuello/genética , Carcinoma de Células Escamosas de Cabeza y Cuello/terapia , Revisiones Sistemáticas como Asunto
6.
Am J Surg Pathol ; 45(5): 604-615, 2021 05 01.
Artículo en Inglés | MEDLINE | ID: mdl-33835080

RESUMEN

Small tumor cell nests such as micropapillary nests are histologic poor prognostic markers for adenocarcinomas of various organs, including the lung. However, for the lung, the association of micropapillary patterns with smoking is controversial, which may be because of a vague definition of micropapillary patterns. This study clarifies the implications of small tumor cell nests by introducing a new dichotomic classification based on the glandular polarity of tumor cells: pure micropapillary nests (pMPs), preserving glandular polarity, and small solid nests (SSNs), lacking polarity. We examined the clinicopathologic factors in 436 resected adenocarcinomas, and analyzed the overall survival between groups classified by either the presence or absence of pMPs and SSNs. pMP was positively associated with nonsmoking-related features such as epidermal growth factor receptor mutations and thyroid transcription factor 1 expression. By contrast, SSN was positively associated with smoking-related features such as KRAS mutations and hepatocyte nuclear factor-4a expressions. Besides, pMP and SSN were significant and independent indicators of poor prognosis in all stages. SSN was an indicator in stage I too, whereas pMP was not. Furthermore, prognoses of the group with SSN were significantly worse than those of pMP-only group. In conclusion, the present study has revealed 2 completely different patterns of small tumor cell nests in lung adenocarcinoma, the nonsmoking-related pMPs, and the smoking-related SSNs, by considering glandular polarity. MPP should include only pMPs, and SSNs should be in a solid pattern. This novel classification might boast clinical significance as a potent poor prognostic marker as well as a factor reflecting etiological and genetic characters.


Asunto(s)
Adenocarcinoma del Pulmón/patología , Neoplasias Pulmonares/patología , Adenocarcinoma del Pulmón/etiología , Adenocarcinoma del Pulmón/mortalidad , Adenocarcinoma del Pulmón/cirugía , Anciano , Biomarcadores de Tumor/análisis , Biomarcadores de Tumor/genética , Femenino , Predisposición Genética a la Enfermedad , Humanos , Neoplasias Pulmonares/etiología , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/cirugía , Masculino , Persona de Mediana Edad , Mutación , Estadificación de Neoplasias , Neumonectomía , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Fumar/efectos adversos , Factores de Tiempo , Resultado del Tratamiento
7.
Anticancer Res ; 41(4): 2133-2140, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33813424

RESUMEN

BACKGROUND/AIM: Tumor-infiltrating lymphocytes (TILs) are considered a prognostic marker for triple-negative breast cancer (TNBC). Immune checkpoint inhibitor (ICI)-based treatments are more effective for tumors with PD-L1-positive TILs, suggesting crucial roles of TILs in the local tumor immunity. However, factors attracting TILs are still largely unknown. Focusing on tumor antigenicity, we examined TNBC samples to identify the characteristics of TIL-high tumors. PATIENTS AND METHODS: Nine treatment-naïve TNBCs (TIL-high: five, TIL-low: four) were subjected to next-generation sequencing (NGS). Loss of heterozygosity (LOH) of PTEN was also analyzed. RESULTS: A variety of copy number variations were observed, and no genes differed significantly between TIL-high and -low groups. However, PTEN loss was more frequently observed in the TIL-high group: 60% compared to 25% in TIL-low tumors. NGS correlated well with LOH analysis in identifying PTEN loss. All three tumors with PTEN loss in the TIL-high group showed high PD-L1. All nine samples were microsatellite-stable. CONCLUSION: Frequent PTEN loss and high expression of PD-L1 in TIL-high TNBC suggest that PTEN mutation may be a biomarker for ICIs.


Asunto(s)
Biomarcadores de Tumor/genética , Linfocitos Infiltrantes de Tumor/metabolismo , Neoplasias de la Mama Triple Negativas/diagnóstico , Neoplasias de la Mama Triple Negativas/genética , Adulto , Anciano , Anciano de 80 o más Años , Antígeno B7-H1/genética , Antígeno B7-H1/metabolismo , Biomarcadores Farmacológicos/análisis , Biomarcadores Farmacológicos/metabolismo , Biomarcadores de Tumor/análisis , Biomarcadores de Tumor/metabolismo , Variaciones en el Número de Copia de ADN , Análisis Mutacional de ADN/métodos , Regulación Neoplásica de la Expresión Génica , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Pérdida de Heterocigocidad , Recuento de Linfocitos , Linfocitos/metabolismo , Linfocitos/patología , Linfocitos Infiltrantes de Tumor/patología , Persona de Mediana Edad , Mutación , Fosfohidrolasa PTEN/genética , Fosfohidrolasa PTEN/metabolismo , Polimorfismo de Nucleótido Simple , Pronóstico , Transcriptoma , Resultado del Tratamiento , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Neoplasias de la Mama Triple Negativas/metabolismo
8.
Nat Commun ; 12(1): 2284, 2021 04 16.
Artículo en Inglés | MEDLINE | ID: mdl-33863904

RESUMEN

Drug resistance is a major obstacle to the treatment of most human tumors. In this study, we find that dual-specificity phosphatase 16 (DUSP16) regulates resistance to chemotherapy in nasopharyngeal carcinoma, colorectal cancer, gastric and breast cancer. Cancer cells expressing higher DUSP16 are intrinsically more resistant to chemotherapy-induced cell death than cells with lower DUSP16 expression. Overexpression of DUSP16 in cancer cells leads to increased resistance to cell death upon chemotherapy treatment. In contrast, knockdown of DUSP16 in cancer cells increases their sensitivity to treatment. Mechanistically, DUSP16 inhibits JNK and p38 activation, thereby reducing BAX accumulation in mitochondria to reduce apoptosis. Analysis of patient survival in head & neck cancer and breast cancer patient cohorts supports DUSP16 as a marker for sensitivity to chemotherapy and therapeutic outcome. This study therefore identifies DUSP16 as a prognostic marker for the efficacy of chemotherapy, and as a therapeutic target for overcoming chemoresistance in cancer.


Asunto(s)
Biomarcadores de Tumor/metabolismo , Fosfatasas de Especificidad Dual/metabolismo , Mitocondrias/efectos de los fármacos , Fosfatasas de la Proteína Quinasa Activada por Mitógenos/metabolismo , Neoplasias/terapia , Adulto , Anciano , Anciano de 80 o más Años , Animales , Antineoplásicos/uso terapéutico , Apoptosis/efectos de los fármacos , Biomarcadores de Tumor/análisis , Biomarcadores de Tumor/genética , Fraccionamiento Celular , Línea Celular Tumoral , Quimioterapia Adyuvante , Cisplatino/farmacología , Cisplatino/uso terapéutico , Supervivencia sin Enfermedad , Resistencia a Antineoplásicos , Fosfatasas de Especificidad Dual/análisis , Femenino , Técnicas de Silenciamiento del Gen , Técnicas de Inactivación de Genes , Humanos , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Masculino , Ratones , Persona de Mediana Edad , Mitocondrias/metabolismo , Fosfatasas de la Proteína Quinasa Activada por Mitógenos/análisis , Neoplasias/mortalidad , Neoplasias/patología , Ensayos Antitumor por Modelo de Xenoinjerto , Proteína X Asociada a bcl-2/metabolismo
9.
BMC Cancer ; 21(1): 265, 2021 Mar 11.
Artículo en Inglés | MEDLINE | ID: mdl-33706745

RESUMEN

BACKGROUND: Gliosarcoma (GSM) is a distinct and aggressive variant of glioblastoma multiforme (GBM) with worse prognosis and few treatment options. It is often managed with the same treatment modalities with temozolomide (TMZ) as in GBM. However, the therapeutic benefits on GSM from such treatment regimen is largely unknown. Patient-derived xenograft (PDX) models have been used widely to model tumor progression, and subsequently to validate biomarkers and inform potential therapeutic regimens. Here, we report for the first time the successful development of a PDX model of secondary GSM. METHODS: Tissue obtained from a tumor resection revealed a secondary GSM arising from GBM. The clinical, radiological, and histopathological records of the patient were retrospectively reviewed. Samples obtained from surgery were cultured ex vivo and/or implanted subcutaneously in immunocompromised mice. Histopathological features between the primary GBM, secondary GSM, and GSM PDX are compared. RESULTS: In explant culture, the cells displayed a spindle-shaped morphology under phase contrast microscopy, consistent with the sarcomatous component. GSM samples were subcutaneously engrafted into immunocompromised mice after single-cell suspension. Xenografts of serial passages showed enhanced growth rate with increased in vivo passage. We did not observe any histopathological differences between the secondary GSM and its serial in vivo passages of PDX tumors. CONCLUSIONS: Our PDX model for GSM retained the histopathological characteristics of the engrafted tumor from the patient. It may provide valuable information to facilitate molecular and histopathological modelling of GSM and be of significant implication in future research to establish precise cancer medicine for this highly malignant tumor.


Asunto(s)
Neoplasias Encefálicas/terapia , Quimioradioterapia/efectos adversos , Glioblastoma/terapia , Gliosarcoma/diagnóstico , Neoplasias Primarias Secundarias/diagnóstico , Animales , Biomarcadores de Tumor/análisis , Biomarcadores de Tumor/genética , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Encéfalo/cirugía , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patología , Proteínas de Ciclo Celular/análisis , Proteínas de Ciclo Celular/genética , Quimioradioterapia/métodos , Craneotomía , Femenino , Glioblastoma/diagnóstico , Glioblastoma/genética , Glioblastoma/patología , Gliosarcoma/etiología , Gliosarcoma/genética , Gliosarcoma/patología , Humanos , Imagen por Resonancia Magnética , Ratones , Persona de Mediana Edad , Mutación , Neoplasias Primarias Secundarias/etiología , Neoplasias Primarias Secundarias/genética , Neoplasias Primarias Secundarias/patología , Cultivo Primario de Células , Temozolomida/uso terapéutico , Células Tumorales Cultivadas , Ensayos Antitumor por Modelo de Xenoinjerto
10.
BMC Cancer ; 21(1): 267, 2021 Mar 12.
Artículo en Inglés | MEDLINE | ID: mdl-33711953

RESUMEN

BACKGROUND: The objective of the study was to detect the expression of Kita-Kyushu lung cancer antigen-1 (KK-LC-1) in gastric cancer (GC) specimens and analyse the associations between KK-LC-1 expression and clinicopathological parameters and clinical prognosis. METHODS: All of the 94 patients in this study were GC patients who underwent surgical resection. KK-LC-1 protein expression in GC tissue was detected by immunohistochemistry. This report applies the histological score (H-score) to evaluate KK-LC-1 expression. To calculate this indicator, the number of positive cells in each section and their staining intensity were converted to corresponding values. The expression of KK-LC-1 in the cytoplasm of cancer and normal tissues was scored to obtain their respective H values. The chi-square test, Kaplan-Meier method and Cox regression were used to analyse the linear association between KK-LC-1 expression and clinicopathological data and prognosis. RESULTS: In the cytoplasm, KK-LC-1 expression in tumour tissues was significantly higher than that in normal tissues (P < 0.001). Using the median H-score as the cut-off value, we discovered that GC patients with high levels of KK-LC-1 expression in the cytoplasm had favourable overall survival (OS) (P = 0.016), and this result was statistically significant in the Cox regression analysis. Additionally, a negative correlation was found between KK-LC-1 protein expression and the pathological grade of the tumour (P = 0.036), with significantly more KK-LC-1 protein expression observed in the intestinal type of GC than in the diffuse type (P = 0.008). CONCLUSIONS: Our research data showed that KK-LC-1 expression was greater in GC tissues than in normal tissues, and higher KK-LC-1 expression was associated with longer OS of GC patients. KK-LC-1 can be used as a biomarker for a good prognosis in GC patients.


Asunto(s)
Antígenos de Neoplasias/metabolismo , Biomarcadores de Tumor/metabolismo , Neoplasias Gástricas/mortalidad , Anciano , Anciano de 80 o más Años , Antígenos de Neoplasias/análisis , Biomarcadores de Tumor/análisis , Femenino , Estudios de Seguimiento , Gastrectomía , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Pronóstico , Medición de Riesgo/métodos , Estómago/patología , Estómago/cirugía , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/patología , Neoplasias Gástricas/cirugía , Factores de Tiempo , Análisis de Matrices Tisulares
11.
BMC Cancer ; 21(1): 277, 2021 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-33722210

RESUMEN

BACKGROUND: As one of the novel molecules, circRNA has been identified closely involved in the pathogenesis of many diseases. However, the function of circRNA in acute myeloid leukemia (AML) still remains unknown. METHODS: In the current study, the RNA expression profiles were obtained from Gene Expression Omnibus (GEO) datasets. The differentially expressed RNAs were identified using R software and the competing endogenous RNA (ceRNA) network was constructed using Cytoscape. Functional and pathway enrichment analyses were performed to identify the candidate circRNA-mediated aberrant signaling pathways. The hub genes were identified by MCODE and CytoHubba plugins of Cytoscape, and then a subnetwork regulatory module was established. RESULTS: A total of 27 circRNA-miRNA pairs and 208 miRNA-mRNA pairs, including 12 circRNAs, 24 miRNAs and 112 mRNAs were included in the ceRNA network. Subsequently, a subnetwork, including 4 circRNAs, 5 miRNAs and 6 mRNAs, was established based on related circRNA-miRNA-mRNA regulatory modules. CONCLUSIONS: In summary, this work analyzes the characteristics of circRNA as competing endogenous RNA in AML pathogenesis, which would provide hints for developing novel prognostic, diagnostic and therapeutic strategy for AML.


Asunto(s)
Biomarcadores de Tumor/metabolismo , Regulación Neoplásica de la Expresión Génica , Redes Reguladoras de Genes , Leucemia Mieloide Aguda/genética , ARN Circular/metabolismo , Biomarcadores de Tumor/análisis , Biología Computacional , Conjuntos de Datos como Asunto , Perfilación de la Expresión Génica , Humanos , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/mortalidad , MicroARNs/metabolismo , Análisis de Secuencia por Matrices de Oligonucleótidos , Pronóstico , Mapeo de Interacción de Proteínas , Mapas de Interacción de Proteínas/genética , ARN Circular/análisis , ARN Mensajero/metabolismo , Transducción de Señal/genética , Análisis de Supervivencia
12.
BMC Cancer ; 21(1): 211, 2021 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-33648471

RESUMEN

BACKGROUND: Meningiomas are common brain tumours that are usually defined by benign clinical course. However, some meningiomas undergo a malignant transformation and recur within a short time period regardless of their World Health Organization (WHO) grade. The current study aimed to identify potential markers that can discriminate between benign and malignant meningioma courses. METHODS: We profiled the metabolites from 43 patients with low- and high-grade meningiomas. Tumour specimens were analyzed by nuclear magnetic resonance analysis; 270 metabolites were identified and clustered with the AutoPipe algorithm. RESULTS: We observed two distinct clusters marked by alterations in glycine/serine and choline/tryptophan metabolism. Glycine/serine cluster showed significantly lower WHO grades and proliferation rates. Also progression-free survival was significantly longer in the glycine/serine cluster. CONCLUSION: Our findings suggest that alterations in glycine/serine metabolism are associated with lower proliferation and more recurrent tumours. Altered choline/tryptophan metabolism was associated with increases proliferation, and recurrence. Our results suggest that tumour malignancy can be reflected by metabolic alterations, which may support histological classifications to predict the clinical outcome of patients with meningiomas.


Asunto(s)
Biomarcadores de Tumor/análisis , Neoplasias Meníngeas/metabolismo , Meningioma/metabolismo , Anciano , Algoritmos , Colina/metabolismo , Análisis por Conglomerados , Progresión de la Enfermedad , Femenino , Glicina/metabolismo , Humanos , Masculino , Neoplasias Meníngeas/química , Neoplasias Meníngeas/mortalidad , Meningioma/química , Meningioma/mortalidad , Persona de Mediana Edad , Clasificación del Tumor , Resonancia Magnética Nuclear Biomolecular , Supervivencia sin Progresión , Serina/metabolismo , Resultado del Tratamiento , Triptófano/metabolismo
13.
Medicine (Baltimore) ; 100(11): e24805, 2021 Mar 19.
Artículo en Inglés | MEDLINE | ID: mdl-33725946

RESUMEN

BACKGROUND: The main purpose of this study is to systematically evaluate the diagnostic value of long-chain non-coding RNA urothelial carcinoembryonic antigen 1 (lncRNA-UCA1) for bladder cancer, and to provide a scientific basis for the diagnosis of bladder cancer. METHODS: By searching PubMed, Web of Science, EMBASE, CNKI, Wanfang, Weipu and other databases, in order to collect relevant literature of lncRNA-UCA1 for diagnosis of bladder cancer. The starting and ending time of the search is from the establishment of the database to December 31, 2019. Screen documents and extract data according to inclusion and exclusion criteria. QUADAS entry tool was used to evaluate the quality of literature. Meta-Disc 1.4 and Stata 12.0 software were used for statistical analysis, and UCA1 was combined for the statistics of bladder cancer diagnosis. RESULTS: A total of 7 articles were included in this study, including 954 cases of bladder cancer patients and 482 cases of non-bladder cancer patients. The receiver operating characteristic curve (ROC) curve AUC of lncRNA-UCA1 used to diagnose bladder cancer was 0.86. The sensitivity was 0.83 (95% CI: 0.80-0.85), and the specificity was 0.86 (95% CI: 0.82-0.89). The positive likelihood ratio is 6.38 (95% CI: 3.01-13.55), and the negative likelihood ratio is 0.20 (95% CI: 0.13-0.31). The diagnostic odds ratio is 33.13 (95% CI: 11.16-98.33). CONCLUSION: lncRNA-UCA1 has a high value of clinical auxiliary diagnosis for bladder cancer, and it can be further promoted and applied clinically.


Asunto(s)
ARN Largo no Codificante/análisis , Neoplasias de la Vejiga Urinaria/diagnóstico , Adulto , Área Bajo la Curva , Biomarcadores de Tumor/análisis , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Valor Predictivo de las Pruebas , Curva ROC , Sensibilidad y Especificidad , Neoplasias de la Vejiga Urinaria/genética
14.
Int J Mol Sci ; 22(5)2021 Feb 26.
Artículo en Inglés | MEDLINE | ID: mdl-33652881

RESUMEN

Senescence marker protein 30 (SMP30) is a cell survival factor playing an important role in vitamin C synthesis and antiapoptosis. Moreover, its cytoprotective role suggests a possibility to be related to cancer cell survival. Mammary carcinoma is a common cancer in both humans and animals. Because of its histopathological diversity, especially in the early stage, histopathological diagnosis may be complicated; therefore, a diagnostic marker is helpful for confirmation. The present study analyzed the expression pattern of SMP30 in mammary carcinoma in humans, dogs, and cats. Immunohistochemistry, immunofluorescence, and western blot analysis were used to investigate SMP30 expression patterns. The expression was specifically observed in neoplastic glandular epithelial cells. The expression increased with the malignancy of glandular epithelial cells with a highly proliferative status. However, SMP30 expression was low in normal mammary gland tissues or well-differentiated adenoma tissues. The patterns were consistently reproduced in canine primary mammary carcinoma cells and MCF-7 and MDA-MB-231 human carcinoma cell lines. This study provides useful information to understand SMP30 expression in various stages of mammary carcinoma and to suggest its utility as a pan-species diagnostic marker, thereby helping to establish strategies for diagnosing mammary carcinoma in several species.


Asunto(s)
Neoplasias de la Mama/patología , Proteínas de Unión al Calcio/análisis , Enfermedades de los Gatos/patología , Enfermedades de los Perros/patología , Péptidos y Proteínas de Señalización Intracelular/análisis , Neoplasias Mamarias Animales/patología , Animales , Biomarcadores de Tumor/análisis , Mama/patología , Neoplasias de la Mama/diagnóstico , Enfermedades de los Gatos/diagnóstico , Gatos , Línea Celular Tumoral , Enfermedades de los Perros/diagnóstico , Perros , Femenino , Humanos , Células MCF-7 , Neoplasias Mamarias Animales/diagnóstico , Pronóstico
15.
Medicine (Baltimore) ; 100(12): e25234, 2021 Mar 26.
Artículo en Inglés | MEDLINE | ID: mdl-33761715

RESUMEN

ABSTRACT: This study investigated the expression change, prognostic values, and potential regulatory mechanisms of mortality factor on chromosome 4 (MORF4)-related gene-binding protein (MRGBP) in hepatocellular carcinoma (HCC).MRGBP expression and clinical data from The Cancer Genome Atlas were used to evaluate the associations between MRGBP expression and clinicopathological characteristics. Kaplan-Meier and Cox regression analyses were performed to assess the factors contributing to prognosis. Gene set enrichment analysis (GSEA) was used to identify pathways associated with MRGBP expression. Single-sample gene set enrichment analysis (ssGSEA) was used to comprehensively analyze the relative immune infiltration levels.High MRGBP expression was significantly associated with a higher T stage, pathologic stage, histologic grade, vascular invasion, tumor protein p53 status, and worse overall survival. MRGBP exhibited high diagnostic accuracy with an area under the receiver operating characteristic curve value of 0.980. GSEA revealed the enrichment of pathways related to tumorigenesis in the MRGBP high-expression phenotype, such as cell cycle and DNA replication pathways. ssGSEA revealed that MRGBP expression was significantly correlated with 15 types of immune cell infiltration levels. The Wilcoxon rank sum test revealed significantly high T helper (Th), T follicular helper, CD56 bright natural killer, and Th2 cell enrichment scores in the high MRGBP expression group and significantly low neutrophil, Th17, dendritic cell (DC), gamma delta T, cytotoxic cell, regulatory T cell, plasmacytoid DC, and immature DC enrichment scores.MRGBP may be a novel prognostic biomarker and a therapeutic target correlated with immune infiltrates in HCC.


Asunto(s)
Carcinoma Hepatocelular , Histona Acetiltransferasas , Neoplasias Hepáticas , Hígado , Proteínas Nucleares , Biomarcadores de Tumor/análisis , Carcinoma Hepatocelular/inmunología , Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/terapia , Biología Computacional/métodos , Femenino , Regulación Neoplásica de la Expresión Génica , Histona Acetiltransferasas/análisis , Histona Acetiltransferasas/genética , Humanos , Estimación de Kaplan-Meier , Hígado/inmunología , Hígado/patología , Neoplasias Hepáticas/inmunología , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/terapia , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Invasividad Neoplásica , Estadificación de Neoplasias , Proteínas Nucleares/análisis , Proteínas Nucleares/genética , Pronóstico
16.
Arq Bras Cir Dig ; 33(4): e1568, 2021.
Artículo en Inglés, Portugués | MEDLINE | ID: mdl-33759958

RESUMEN

BACKGROUND: A) CD133+ cytoplasmic B) AXL+ combined C) c-MYC+ nuclear. CD133 and AXL have been described as cancer stem cell markers, and c-MYC as a key regulatory cellular mechanism in colorectal cancer (CRC). AIM: Evaluate the prognostic role of the biomarkers CD133, AXL and c-MYC and their association with clinicopathologic characteristics in colorectal adenocarcinomas and adenomas. METHODS: A total of 156 patients with UICC stage I-IV adenocarcinomas (n=122) and adenomas (n=34) were analyzed. Tissue microarrays (TMA) from primary tumors and polyps for CD133, c-MYC and AXL expression were performed and analyzed for their significance with clinicopathologic characteristics. RESULTS: Poorly differentiated adenocarcinomas and disease progression were independent risk factors for poor overall survival. The median overall survival time was 30 months. Positive CD133 expression (35.9% of all cases), particularly of right-sided CRCs (44.8% of the CD133+ cases), was negatively correlated with death in the univariate analysis, which did not reach significance in the multivariate analysis. c-MYC (15.4% of all cases) was predominantly expressed in advanced-stage patients with distant (non-pulmonary/non-hepatic) metastasis. AXL expression was found only occasionally, and predominantly dominated in adenomas, with less penetrance in high-grade dysplasia. CONCLUSIONS: CD133 expression was not associated with inferior overall survival in CRC. While AXL showed inconclusive results, c-MYC expression in primary CRCs was associated with distant metastasis.


Asunto(s)
Antígeno AC133 , Biomarcadores de Tumor , Neoplasias Colorrectales , Antígeno AC133/análisis , Biomarcadores de Tumor/análisis , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/patología , Femenino , Humanos , Masculino , Metástasis de la Neoplasia , Células Madre Neoplásicas/metabolismo , Pronóstico , Proteínas Proto-Oncogénicas c-myc/metabolismo
17.
Methods Mol Biol ; 2292: 105-113, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33651355

RESUMEN

Prostate cancer antigen 3 (PCA3) is a urinary biomarker for prostate cancer and has demonstrated a good specificity and sensitivity representing a minimally invasive test.PCA3 assay could be useful in combination with PSA to suggest an eventual rebiopsy in men who have had one or more previous negative prostate biopsies.Combination of multiple tumor biomarkers will be the trend in the near future to achieve the goal of evaluate the aggressiveness of cancer and at the same time reducing the number of unnecessary biopsies.


Asunto(s)
Antígenos de Neoplasias/análisis , Próstata/patología , Neoplasias de la Próstata/diagnóstico , Biomarcadores de Tumor/análisis , Biopsia/métodos , Humanos , Masculino
18.
Methods Mol Biol ; 2292: 115-120, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33651356

RESUMEN

The analysis of liquid biopsy as a source of diagnostic, prognostic, and predictive biomarkers is still object of the main research in the prostate cancer field. Many advantages, such as less invasiveness compared to plasma or serum analysis and the rich content, confer to urine a role as an interesting fluid to be analysed especially in urological diseases. Here we report a workflow focused on profile, concentration, and protein surface characterization of EVs from urinary supernatant.


Asunto(s)
Exosomas/patología , Neoplasias de la Próstata/diagnóstico , Biomarcadores de Tumor/análisis , Biomarcadores de Tumor/orina , Humanos , Biopsia Líquida/métodos , Masculino , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/orina , Proteínas/análisis , Proteinuria/diagnóstico , Proteinuria/patología , Proteinuria/orina , Toma de Muestras de Orina/métodos , Flujo de Trabajo
19.
Am J Surg Pathol ; 45(5): 616-626, 2021 05 01.
Artículo en Inglés | MEDLINE | ID: mdl-33729740

RESUMEN

Epithelioid hemangioendothelioma (EHE) is a rare vascular endothelial neoplasm with characteristic histology and distinctive fusion genes. Its clinical presentation and outcome are heterogeneous, and the determinants of survival are controversial. In this study, we aimed to identify clinicopathologic prognostic factors of EHE in a retrospective cohort of 62 cases with CAMTA1/TFE3/WWTR1 alterations. The tumors were of the CAMTA1 subtype for 59 cases, TFE3 subtype for 2 cases, and variant WWTR1 subtype (WWTR1-ACTL6A) for 1 case. Twenty-two tumors (35.5%) demonstrated atypical histology, defined by having at least 2 of the following 3 findings: high mitotic activity (>1/2 mm2), high nuclear grade, and coagulative necrosis. During a median follow-up of 34 months, 11 patients (18%) died, and the 5-year overall survival rate was 78.8%. Survival did not correlate with such clinical parameters as age, sex, tumor sites, multifocality, and multiorgan involvement. Conversely, based on both univariate and multivariate analyses, large tumor size (>30 mm) and histologic atypia were significantly associated with a shorter survival. A proposed 3-tiered risk assessment system using these 2 parameters significantly stratified the patients into low-risk, intermediate-risk, and high-risk groups with 5-year overall survival rates of 100%, 81.8%, and 16.9%, respectively (P<0.001). Four tumors (6.4%) expressed synaptophysin, which all belonged to the high-risk group and pursued an aggressive course. The present study demonstrated the independent prognostic significance of large tumor size and atypical histology in EHE, as well as the value of risk stratification using these 2 factors. Moreover, we revealed a small EHE subset with aberrant synaptophysin expression, which may have potential prognostic and diagnostic implications.


Asunto(s)
Biomarcadores de Tumor/análisis , Hemangioendotelioma Epitelioide/química , Sinaptofisina/análisis , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/genética , Femenino , Hemangioendotelioma Epitelioide/genética , Hemangioendotelioma Epitelioide/mortalidad , Hemangioendotelioma Epitelioide/patología , Humanos , Inmunohistoquímica , Hibridación Fluorescente in Situ , Masculino , Persona de Mediana Edad , Mitosis , Necrosis , Clasificación del Tumor , Valor Predictivo de las Pruebas , RNA-Seq , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Factores de Tiempo , Adulto Joven
20.
Am J Surg Pathol ; 45(5): 701-707, 2021 05 01.
Artículo en Inglés | MEDLINE | ID: mdl-33739790

RESUMEN

Suppression of the immune system is intimately linked to the development and progression of malignancy, and immune modulating treatment options have shown promise in a variety of tumor types, including some triple-negative breast cancers (TNBC). The most dramatic therapeutic success has been seen with immune checkpoint inhibitors targeting programmed cell death protein 1 (PD-1) and its ligand, PD-L1. Difficulty remains, however, in appropriate patient selection for treatment, as many PD-L1-positive cancers fail to show durable responses to PD-1/PD-L1 inhibition. Checkpoint inhibitor targeting of the adaptive immune response relies on the presence of major histocompatibility complex (MHC) class I molecules on the tumor cell surface for tumor antigen presentation. MHC class I loss has been previously described in breast cancer and represents a putative mechanism of immunotherapeutic resistance in this tumor type. One hundred seventeen invasive primary breast carcinomas with a range of histologic subtypes were evaluated on tissue microarrays containing formalin-fixed paraffin-embedded tissue. Loss of MHC class I expression was common among breast cancers, with greater than half of cases demonstrating either subclonal or diffuse loss. Fifty-nine percent of TNBC demonstrated loss of MHC class I, including 46% of those meeting the Food and Drug Administration-approved threshold of 1% for tumor-associated immune cell PD-L1 expression. MHC class I loss was particularly common in the apocrine subtype of TNBC (78%). MHC class I's employment as a predictive biomarker should be considered, as its loss may represent a barrier to successful enhancement of the antitumor adaptive immune response by PD-1/PD-L1 inhibition.


Asunto(s)
Antígeno B7-H1/análisis , Biomarcadores de Tumor/análisis , Antígenos de Histocompatibilidad Clase I/análisis , Receptor de Muerte Celular Programada 1/análisis , Neoplasias de la Mama Triple Negativas/inmunología , Inmunidad Adaptativa , Adulto , Anciano , Anciano de 80 o más Años , Antígeno B7-H1/antagonistas & inhibidores , Biomarcadores de Tumor/antagonistas & inhibidores , Femenino , Humanos , Inmunohistoquímica , Persona de Mediana Edad , Selección de Paciente , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Análisis de Matrices Tisulares , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Neoplasias de la Mama Triple Negativas/patología , Microambiente Tumoral
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