ABSTRACT
Abstract Cancer is a fatal malignancy and its increasing worldwide prevalence demands the discovery of more sensitive and reliable molecular biomarkers. To investigate the GINS1 expression level and its prognostic value in distinct human cancers using a series of multi-layered in silico approach may help to establish it as a potential shared diagnostic and prognostic biomarker of different cancer subtypes. The GINS1 mRNA, protein expression, and promoter methylation were analyzed using UALCAN and Human Protein Atlas (HPA), while mRNA expression was further validated via GENT2. The potential prognostic values of GINS1 were evaluated through KM plotter. Then, cBioPortal was utilized to examine the GINS1-related genetic mutations and copy number variations (CNVs), while pathway enrichment analysis was performed using DAVID. Moreover, a correlational analysis between GINS1 expression and CD8+ T immune cells and a the construction of gene-drug interaction network was performed using TIMER, CDT, and Cytoscape. The GINS1 was found down-regulated in a single subtypes of human cancer while commonly up-regulated in 23 different other subtypes. The up-regulation of GINS1 was significantly correlated with the poor overall survival (OS) of Liver Hepatocellular Carcinoma (LIHC), Lung Adenocarcinoma (LUAD), and Kidney renal clear cell carcinoma (KIRC). The GINS1 was also found up-regulated in LIHC, LUAD, and KIRC patients of different clinicopathological features. Pathways enrichment analysis revealed the involvement of GINS1 in two diverse pathways, while few interesting correlations were also documented between GINS1 expression and its promoter methylation level, CD8+ T immune cells level, and CNVs. Moreover, we also predicted few drugs that could be used in the treatment of LIHC, LUAD, and KIRC by regulating the GINS1 expression. The expression profiling of GINS1 in the current study has suggested it a novel shared diagnostic and prognostic biomarker of LIHC, LUAD, and KIRC.
Resumo O câncer é uma doença maligna fatal e sua crescente prevalência mundial exige a descoberta de biomarcadores moleculares mais sensíveis e confiáveis. Investigar o nível de expressão de GINS1 e seu valor prognóstico em cânceres humanos distintos, usando uma série de abordagens in silico em várias camadas, pode ajudar a estabelecê-lo como um potencial biomarcador de diagnóstico e prognóstico compartilhado de diferentes subtipos de câncer. O mRNA de GINS1, a expressão da proteína e a metilação do promotor foram analisados usando UALCAN e Human Protein Atlas (HPA), enquanto a expressão de mRNA foi posteriormente validada via GENT2. Os valores prognósticos potenciais de GINS1 foram avaliados por meio do plotter KM. Em seguida, o cBioPortal foi utilizado para examinar as mutações genéticas relacionadas ao GINS1 e as variações do número de cópias (CNVs), enquanto a análise de enriquecimento da via foi realizada usando DAVID. Além disso, uma análise correlacional entre a expressão de GINS1 e células imunes T CD8 + e a construção de uma rede de interação gene-droga foi realizada usando TIMER, CDT e Cytoscape. O GINS1 foi encontrado regulado negativamente em um único subtipo de câncer humano, enquanto comumente regulado positivamente em 23 outros subtipos diferentes. A regulação positiva de GINS1 foi significativamente correlacionada com a sobrevida global pobre (OS) de Carcinoma Hepatocelular de Fígado (LIHC), Adenocarcinoma de Pulmão (LUAD) e Carcinoma de Células Claras Renais de Rim (KIRC). O GINS1 também foi encontrado regulado positivamente em pacientes LIHC, LUAD e KIRC de diferentes características clínico-patológicas. A análise de enriquecimento de vias revelou o envolvimento de GINS1 em duas vias diversas, enquanto poucas correlações interessantes também foram documentadas entre a expressão de GINS1 e seu nível de metilação do promotor, nível de células imunes T CD8 + e CNVs. Além disso, também previmos poucos medicamentos que poderiam ser usados no tratamento de LIHC, LUAD e KIRC, regulando a expressão de GINS1. O perfil de expressão de GINS1 no estudo atual sugeriu que é um novo biomarcador de diagnóstico e prognóstico compartilhado de LIHC, LUAD e KIRC.
Subject(s)
Humans , Carcinoma, Renal Cell/genetics , Kidney Neoplasms/genetics , Liver Neoplasms , Prognosis , Biomarkers, Tumor/genetics , Gene Expression Regulation, Neoplastic , Up-Regulation , DNA-Binding Proteins , DNA Copy Number VariationsABSTRACT
Introducción. El cistoadenoma mucinoso biliar es una neoplasia rara con alta probabilidad de malignidad. Su diagnóstico es un reto ya que se asemeja a otras masas benignas que pueden encontrarse en el hígado. Caso clínico. Mujer de 21 años con sensación de masa en hipocondrio derecho, a quien se le realizan marcadores tumorales y estudios de imágenes concluyendo que se trataba de un cistadenoma mucinoso biliar. Resultado. Se presenta el caso de una paciente con cistoadenoma mucinoso biliar, diagnosticada y tratada exitosamente con cirugía. Conclusión. El diagnóstico de cistoadenoma mucinoso biliar se confirma mediante marcadores tumorales y estudios radiológicos, y su tratamiento es quirúrgico debido al riesgo de malignidad
Introduction. Biliary mucinous cystadenoma is a rare neoplasm with a high probability of malignancy. Its diagnosis is a challenge since it resembles other benign masses that can be found in the liver. Clinical case. A 21-year-old woman with a sensation of a mass in the right hypochondrium, who underwent tumor markers and imaging studies, concluding with a diagnosis of biliary mucinous cystadenoma. Result. A case of a patient with biliary mucinous cystadenoma diagnosed and successfully treated by surgery is presented. Conclusion. The diagnosis of biliary mucinous cystadenoma is confirmed by tumor markers and radiological studies, and its treatment is surgical due to the risk of malignancy
Subject(s)
Humans , Biomarkers, Tumor , Cystadenoma, Mucinous , Liver Neoplasms , Immunohistochemistry , Hepatomegaly , LiverABSTRACT
Objective To compare the financial and time cost of breast cancer biomarker analysis by immunohistochemistry with that by the Xpert® STRAT4 assay. Methods We estimated costs (personnel, location, consumables and indirect) and time involved in breast cancer diagnosis at the Butaro Cancer Centre of Excellence, Rwanda, using time-driven activity-based costing. We performed a cost-minimization analysis to compare the cost of biomarker analysis for estrogen receptor, progesterone receptor and human epidermal growth factor receptor-2 status with immunohistochemistry versus STRAT4. We performed sensitivity analyses by altering laboratory-specific parameters for the two methods. Findings We estimated that breast cancer diagnosis in Rwanda costs 138.29 United States dollars (US$) per patient when conducting biomarker analysis by immunohistochemistry. At a realistic immunohistochemistry antibody utilization efficiency of 70%, biomarker analysis comprises 48.7% (US$ 67.33) of diagnostic costs and takes 33 min. We determined that biomarker analysis with STRAT4 yields a reduction in diagnosis cost of US$ 7.33 (10.9%; 7.33/67.33), and in pathologist and technician time of 20 min (60.6%; 20/33), per patient. Our sensitivity analysis revealed that no cost savings would be made in laboratories with antibody utilization efficiencies over 90%, or where only estrogen and/or progesterone receptor status are assessed; however, such operational efficiencies are unlikely, and more laboratories are pursuing human epidermal growth factor receptor-2 analysis as targeted therapies become increasingly available. Conclusion Breast cancer biomarker analysis with STRAT4 has the potential to reduce the required human and capital resources in subSaharan African laboratories, leading to improved treatment selection and better clinical outcomes.
Subject(s)
Humans , Male , Female , Breast Neoplasms , Immunohistochemistry , Biomarkers, Tumor , Diagnosis , RNA, Messenger , Estrogens , Pathology, Molecular , GeneticsABSTRACT
Background: Hepatocellular carcinoma (HCC) is one of the most diagnosed cancers worldwide. Chemoprevention of HCC can be achieved using natural or synthetic compounds that reverse, suppress, detect, or prevent cancer progression. Objectives: In this study, both the antiproliferative effects and luminescent properties of 2'-hydroxychalcones were evaluated. Methods: Cell viability was evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) colorimetric assay, spectroscopy assays, and density functional theory (DFT) calculations were used to determine the luminescent properties of 2 Ì-hydroxychalcones. Results: Cytotoxic effects of 2 Ì-hydroxychalcones were observed over the HepG2 and EA.hy926 cells. Since the chalcone moiety could be used as a fluorescent probe, these compounds may be helpful in cancer diagnosis and tumor localization. They may enable tumor observation and regression through the fluorescence during treatment; therefore, the compounds are a potential candidate as novel anticancer agents acting on human hepatomas. Conclusions: This report describes the chalcones' use as a specific luminescent biomarker in tumor cells. We also report the cellular uptake of 2'-hydroxychalcones, their cellular distribution, and the mechanisms that may be responsible for their cytotoxic effects
ANTECEDENTES: El carcinoma hepatocelular (CHC) es uno de los cánceres más diagnosticados en todo el mundo. La quimio prevención del CHC se puede lograr utilizando compuestos naturales o sintéticos que reviertan, supriman, detecten o prevengan la progresión del cáncer. OBJETIVOS: En este estudio, se investigó tanto los efectos antiproliferativos como las propiedades luminiscentes de las 2'-hidroxicalconas. MÉTODOS: La viabilidad celular se evaluó usando el ensayo colorimétrico (MTT), los ensayos de espectroscopia y los cálculos DFT se usaron para determinar las propiedades luminiscentes de las 2 Ì-hidroxichalconas. RESULTADOS: Se observaron efectos citotóxicos sobre las líneas celulares del tipo HepG2 y EA.hy926. Dado que la estructura de la 2 Ì-hidroxichalcona puede ser usada como sonda fluorescente, estos compuestos pueden ser útiles en el diagnóstico del cáncer y la localización del tumor, ya que pueden permitir la observación a través de la fluorescencia y la regresión del tumor durante el tratamiento, por lo que son candidatas potenciales como nuevos agentes anticancerígenos que podrían actuar sobre hepatomas humanos. CONCLUSIONES: Este trabajo describe el uso de las 2 Ì-hidroxichalconas como un biomarcador luminiscente específico para células tumorales. También informamos la captación celular de 2>-hidroxicalconas, su distribución celular y los mecanismos que pueden ser responsables de sus efectos citotóxicos
Subject(s)
Humans , Biomarkers, Tumor , Cell Survival/drug effects , Chalcones/pharmacology , Luminescent Agents , Antineoplastic Agents/pharmacology , Hep G2 Cells/drug effectsABSTRACT
Colorectal cancer (CRC) is the third most prevalent cancer and the second most common cause of cancer death; however, its early detection can improve the survival. Colonic polyps are considered one of the CRC's major risk factors. Throughout many biological processes and malignancies, the non-coding RNAs have essential functions. Certain long noncoding RNAs (lncRNAs), including H19, were supposed to be CRC possible biomarkers. Also, H19 has been reported to play a role in regulating the activity of beta-catenin, a protein that regulates cell-to-cell adhesion, as well as gene transcription. The current work aimed to investigate the potential significance of LncRNA H19 relative serum expression level by quantitative polymerase chain reaction (q-PCR) and beta-catenin by enzyme-linked immunosorbent assay (ELISA) as noninvasive biomarkers to discriminate between colorectal cancer and colonic polyps. The statistical analysis of the studied factors revealed that the serum expression of H19 and beta-catenin in cancer cases were substantially greater than colonic polyp cases and normal control. Conclusion: The relative expressions of H19 and beta-catenin in the serum can significantly discriminate patients with CRC from those with polyp and normal controls, which could help when screening for CRC. (AU)
Subject(s)
Humans , Male , Female , Adult , Middle Aged , Aged , Biomarkers, Tumor , beta Catenin , RNA, Long Noncoding , Colorectal Neoplasms/diagnosis , Early Detection of CancerABSTRACT
Background: Colorectal cancer (CRC) is the third most prevalent type of cancer worldwide, and is one of the major health problems in Asia, Africa, Europe, and America. The tumor antigens recently are of interesting indicators as diagnostic and prognostic tools, The aim of the present study is to detect the expression levels of carbonic anhydrase IX (CA9), the Wilms tumor gene (WT1), and the preferentially expressed antigen in melanoma (PRAME) in the peripheral blood of CRC patients in comparison with healthy controls. Methods: A prospective case-control study of CRC patients was conducted. We included 25 newly-diagnosed CRC eligible patients and obtained peripheral blood samples of them as well as 10 blood samples from the control group. All samples were then submitted to deoxyribonucleic acid (DNA) extraction and a molecular study through real-time polymerase chain reaction (PCR). Results: The CRC group consisted of 15 (60%) female and 10 (40%) male patients with a mean age of 50.52 ± 9.8 years, while the control group included 4 (40%) female and 6 (60%) male patients with a mean age of 47.7 ± 7.9 years. The CRC group, 24 (96%) of patient samples were CA9-positive with strong statistically significant differences (p < 0.00001; sensitivity: 96%; specificity: 90%). Regarding the WT1 gene, there were 11 (44%) positive samples in the CRC group, with no statistically significant differences (p = 0.055; sensitivity: 44%; specificity: 90%). The PRAME gene was positive in 9 (36%) samples in the CRC group, with no statistically significant differences (p = 0.357; sensitivity: 36%; specificity: 80%. Among CA9 (24 patients; 96%) of patients with CRC expressed positive results, in WT1 11(91.6%) CRC patients expressed gene, and in PRAME gene, 9 patients with CRC (81.8%) expressed positive results. Conclusion: Overexpression of the CA9 gene in CRC of high sensitivity and specificity to be used as a tool to discriminate CRC from benign associate with high accuracy compare to WT1 and PRAME genes. (AU)
Subject(s)
Humans , Male , Female , Adult , Middle Aged , Colorectal Neoplasms/diagnosis , Biomarkers, Tumor , WT1 Proteins/genetics , Carbonic Anhydrase IX/genetics , Antigens, Neoplasm/genetics , Prognosis , Case-Control Studies , Gene Expression , Prospective Studies , Reverse Transcriptase Polymerase Chain ReactionABSTRACT
Introducción: La relación entre supervivencia e infiltración linfocitaria en el cáncer gástrico se ha determinado como factor pronóstico beneficioso, este estudio local tiene como objetivo determinar la probabilidad de supervivencia en los pacientes con cáncer gástrico estadios IB al IIIC de acuerdo con el porcentaje de infiltración linfocitaria tumoral. Metodología: El presente estudio longitudinal se realizó en el Hospital Oncológico Solón Espinosa Ayala Solca-Núcleo de Quito. El período de estudio de enero del 2013 a enero del 2016, el tiempo de seguimiento terminó en diciembre del 2018. El cálculo de la muestral fue no probabilístico en donde se incluyeron casos de pacientes mayores a 18 años con diagnóstico de cáncer gástrico con estadios clínicos IB al IIIC, que contaron con una muestra histopatológica de gastrectomías. Se usó la variable: "Porcentaje de infiltración" para el análisis la muestra y se dividió en 3 grupos: G1: infiltración linfocitaria leve, G2: moderada y G3: intensa. Las estimaciones de supervivencia se calcularon utilizando el método de Kaplan-Meier y la comparación entre los grupos con la prueba de rango logarítmico. Resultados: 173 pacientes con cáncer gástrico con estadios clínicos IB al IIIC, seguidos a 72 meses, el 60 % son hombres y el 40 % mujeres. Según el porcentaje de infiltración linfocitaria, el 52 % reportaron un porcentaje de infiltración leve, el 21 % moderada y el 27 % intensa. A los 72 meses de seguimiento la supervivencia en G1 fue del 31 %, en G2 fue del 48 %, y en G3 fue del 77 % (P= 0.001). Conclusión: Se encontró que el grado de infiltración linfocitaria intensa en los pacientes con cáncer gástrico estuvo asociado a una mejor supervivencia en el seguimiento a 72 meses.
Introduction: The relationship between survival and lymphocytic infiltration in gastric cancer has been determined to be a beneficial prognostic factor. This local study aims to assess the probability of survival in patients with gastric cancer stages IB to IIIC according to the percentage of lymphocytic infiltration. Methodology: This longitudinal study was conducted at the Solón Espinosa Ayala Solca-Núcleo Cancer Hospital in Quito. The study period was from January 2013 to January 2016; the follow-up time ended in December 2018. The sample calculation was nonprobabilistic and included cases of patients older than 18 diagnosed with gastric cancer with clinical stages IB at IIIC, which had a histo-pathological sample of gastrectomies. The variable "percentage of infiltration" was used to analyze the sample, and it was divided into three groups: G1: mild lymphocytic infiltration, G2: moderate, and G3: intense. Survival estimates were calculated using the KaplanMeier method and compared groups with the log-rank test. Results: A total of 173 patients with gastric cancer with clinical stages IB to IIIC were followed up for 72 months; 60% were men, and 40% were women. According to the percentage of lymphocytic infil-tration, 52% reported a rate of mild infiltration, 21% moderate, and 27% intense. At 72 months of follow-up, survival was 31% in G1, 48% in G2, and 77% in G3 (P= 0.001). Conclusion: The degree of intense lymphocytic infiltration in gastric cancer patients was associated with better survival at the 72-month follow-up.
Subject(s)
Humans , Adult , Aged , Stomach Neoplasms , Survival , Lymphocytes, Tumor-Infiltrating , Biomarkers, Tumor , Survival AnalysisABSTRACT
SUMMARY OBJECTIVE: A growing volume of literature has suggested long noncoding RNAs (lncRNAs) as important players in tumor progression. In this study, we aimed to investigate the expression and prognostic value of lncRNA LINC00173 (LINC00173) in melanoma. METHODS: LINC00173 expression was measured in 163 paired cancerous and noncancerous specimen samples by real-time polymerase chain reaction. The correlations between LINC00173 expression with clinicopathological characteristics and prognosis were analyzed by chi-square test, log-rank test, and multivariate survival analysis. Receiver-operating characteristic curves were used for the assessment of the diagnostic value of LINC00173 for melanoma patients. RESULTS: The expression level of LINC00173 in melanoma specimens was distinctly higher than that in adjacent non-neoplasm specimens (p<0.01). Besides, LINC00173 was expressed more frequently in patients with advanced melanoma than in patients with early melanoma. Multivariate assays confirmed that LINC00173 expression level was an independent prognostic predictor of melanoma patients (p<0.05). CONCLUSION: Our data indicated that LINC00173 expression could serve as an unfavorable prognostic biomarker for melanoma patients.
Subject(s)
Humans , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , Melanoma/diagnosis , Melanoma/genetics , Prognosis , Biomarkers, Tumor/genetics , Gene Expression Regulation, Neoplastic , Kaplan-Meier EstimateABSTRACT
O carcinoma de células escamosas (OSCC) é uma neoplasia maligna que atinge a cavidade oral, lábios e orofaringe com uma das maiores taxa de mortalidade em todo o mundo, quando em comparação com outros carcinomas, o que o torna um problema de saúde pública (MORO, 2018). Devido à sua grande prevalência, os pesquisadores buscam por mecanismos para aprimorar o diagnóstico da doença em sua fase inicial, no intuito de possibilitar melhor qualidade de vida e sobrevida a esses pacientes (CHENG et al., 2014). Tem-se desenvolvido estudos através da expressão de proteínas, envolvendo o mecanismo biomolecular da carcinogênese oral na busca de identificação de biomarcadores que tenham potencial preditivo e um bom prognóstico para OSCC (CARVALHO; OLIVEIRA, 2015; LOUSADA-FERNANDEZ et at., 2018). Em uma revisão sobre o genoma salivar do câncer oral, este destacou-se justamente pelo fato de suas proteínas estarem localmente expressas (SHAH et at., 2011), tornando seus biomarcadores salivares de fácil e rápida coleta, já que a proliferação desordenada de células malignas deixa derivados de DNA, RNA, vesiculas (exossomos) e marcadores proteicos nos fluidos creviculares, podendo demostrar de forma preventiva o câncer. Com isso, esses biomarcadores podem ser identificados na fase inicial da doença, ao contrário do exame clínico, já que as manifestações clínicas são tardias, o que gera um prognóstico ruim (LOUSADA-FERNANDEZ et al., 2018). Diante desse quadro, o objetivo deste trabalho foi fazer uma revisão de literatura acerca do papel dos biomarcadores tumorais e discutir sobre a atual situação do câncer bucal, justificando o uso de biomarcadores salivares e entendendo seu papel no diagnóstico precoce. Para isso foi feita uma busca detalhada nas bases de dados Pubmed-Medline, Biblioteca Virtual em Saúde, Lilacs e Scielo, para identificar os mais recentes biomarcadores citados nas literaturas ultilizando as palavras-chaves: carcinoma, biomarcadores, saliva. Também foram incluídos dados coletados da Organização Mundial da Saúde e do Instituto Nacional do Câncer.
Subject(s)
Saliva , Mouth Neoplasms , Carcinoma, Squamous Cell , Biomarkers, TumorABSTRACT
Dentre os subtipos de câncer de mama, o triplo negativo (TNBC) é o que apresenta as maiores taxas de mortalidade, sendo, portanto, considerado um enorme desafio para a clínica. O uso de moléculas como marcadores tumorais vem auxiliando o clínico no diagnóstico, no prognóstico e, até mesmo, no tratamento do TNBC, sendo essenciais na redução de suas altas taxa de mortalidade. No entanto, um pequeno grupo de marcadores tumorais são validados na prática clínica, estimulando à busca por novos alvos, e sua caracterização funcional, como forma de se entender a Biologia desta doença. Assim, o objetivo deste trabalho é caracterizar funcionalmente o gene codificador de proteína CD14 e o gene não codificador de proteína LINC01133 em linhagens celulares humanas de TNBC, no intuito de descobrir o papel destas moléculas na progressão tumoral. Na primeira parte deste trabalho, analisou-se a expressão do CD14 frente à um painel de linhagens celulares que representam os diferentes subtipos dos tumores mamários. O CD14 exibiu elevados níveis de expressão nas linhagens nãotumorigênicas MCF10A e MCF12A e baixos níveis na linhagem triplo negativa Hs578T. A partir destes resultados, o CD14 foi superexpresso na linhagem Hs578T. Ensaios de caracterização funcional mostraram que a superexpressão do CD14 reduziu a capacidade migratória e invasiva das células, efeito que foi hipoteticamente relacionado ao aumento da expressão da E-caderina. No entanto, observou-se aumento no potencial tumorigênico, levando-nos a sugerir seu envolvimento num possível mecanismo utilizado pelas células para compensar a significativa redução do potencial migratório e invasivo. Os resultados obtidos indicam que o nível basal de expressão do CD14 observado na linhagem Hs578T é importante, podendo contribuir para a desenvolvimento primário do tumor, atuando como um oncogene. Na segunda parte deste trabalho, analisou-se a expressão de 10 RNAs longos não codificadores (lncRNAs), frente ao mesmo painel de linhagens descritoanteriormente. Dentre estes, o lncRNA LINC01133 exibiu baixos níveis de expressão nas linhagens não-tumorigênicas MCF10A e MCF12A e elevados níveis na linhagem triplo negativa Hs578T, sendo, então, escolhido como alvo de estudo. A partir destes resultados, decidimos superexpressar, de forma indutível, o LINC01133 na linhagem MCF10A e nocautear este gene, via sistema CRISPR/Cas9, na linhagem Hs578T. Ensaios de caracterização funcional mostraram que a superexpressão do LINC01133 na linhagem MCF10A reduziu a proliferação celular e inibiu o crescimento de colônias dependente de ancoragem, mas, em contrapartida, aumentou o crescimento de colônias independente de ancoragem e a capacidade migratória e invasiva destas células. No entanto, sugerimos que isto não seja suficiente para tornar estas células tumorigênicas e metastáticas. Por outro lado, o nocauteamento do LINC01133 na linhagem triplo negativa Hs578T aumentou de forma considerável todos os parâmetros de malignidade analisados. Baseado nos dados obtidos, sugerimos que o elevado nível de expressão do LINC01133 na linhagem Hs578T é importante na regulação negativa de processos relacionados com a progressão tumoral, atuando com um supressor tumoral. Os dados obtidos em nosso estudo contribuem para o enriquecimento de informações relacionadas à Biologia do TNBC, auxiliando, desta forma, no desenvolvimento de potenciais protocolos clínicos e terapêuticos utilizandos estes biomarcadores
Among the breast cancer subtypes, the triple negative (TNBC) displays the highest mortality rates, being, therefore, considered a major challenge for the clinic. The use of molecules as tumor markers has helped clinicians in the diagnosis, prognosis and even in treatment of TNBC, being essential in reducing its high mortality rate. However, a small group of tumor markers is validated in clinical practice, stimulating the search for new targets, and their functional characterization, as a way to understand the biology of this disease. Thus, the aim of this work is to functionally characterize the CD14 protein-coding gene and the non-protein-coding LINC01133 gene in human TNBC cell lines, in order to probe into the role of these molecules in tumor progression. In the first part of this work, the expression of CD14 was analyzed in a panel of cell lines that represent the different subtypes of breast tumors. High expression levels of CD14 were observed in the non-tumorigenic MCF10A and MCF12A lineages and low levels in the triple negative Hs578T lineage. Based on these results, CD14 was overexpressed in the Hs578T lineage. Functional characterization assays showed that CD14 overexpression reduced the migratory and invasive capacity of cells, an effect that was hypothetically related to increased E-cadherin expression. However, increased in the tumorigenic potential was observed, leading us to suggest its involvement in a possible mechanism used by cells to compensate for the significant reduction in the migratory and invasive potential. The results obtained indicate that CD14 expression basal level observed in the Hs578T lineage may be important to contribute to the primary development of tumor, thus acting as an oncogene. In the second part of this work, the expression of 10 long non-coding RNAs (lncRNAs) was analyzed against the same lineage panel described above. Among these, the LINC01133 lncRNA exhibited low expression levels in the non-tumorigenic MCF10A and MCF12A lineages and high levels in the triple negative Hs578T lineage, being, then, chosen as a target for this study. Based on these results, we decided toinducibly overexpress LINC01133 in the MCF10A lineage and knockout this gene, via the CRISPR/Cas9 system, in the Hs578T lineage. Functional characterization assays showed that overexpression of LINC01133 in the MCF10A lineage reduced cell proliferation and inhibited anchorage-dependent colony growth, but, on the other hand, increased anchorage-independent colony growth and the migratory and invasive capacity of these cells. However, we suggest that this is not sufficient to render these cells tumorigenic and metastatic. On the other hand, the knockout of LINC01133 in the triple negative Hs578T lineage considerably increased all the analyzed malignancy parameters. Based on the results obtained, we suggest that the high expression level of LINC01133 in the Hs578T lineage is important for down-regulation of processes related to tumor progression, acting as a tumor suppressor. The data obtained in our study contribute to the enrichment of information related to TNBC Biology, thus assisting in the development of potential clinical and therapeutic protocols using these biomarkers
Subject(s)
Biomarkers/analysis , Biomarkers, Tumor/analysis , Cells/chemistry , Triple Negative Breast Neoplasms/pathology , Cell Line , Growth and DevelopmentABSTRACT
El antígeno específico de próstata (PSA, del inglés, Prostate Specific Antigen) es una glicoproteína producida por la próstata, y es el marcador tumoral de mayor uso. Sin embargo, su baja especificidad para diferenciar entre cáncer de próstata y otras alteraciones no malignas, como la hipertrofia benigna de la próstata (HBP) y la prostatitis aguda, limitan su utilidad diagnóstica
Prostate Specific Antigen (PSA) is a glycoprotein produced by the prostate and is the most widely used tumor marker. However, its low specificity to differentiate between prostate cancer and other non-malignant conditions, such as benign prostate hypertrophy (BPH) and acute prostatitis, limits its diagnostic utility
Subject(s)
Prostate-Specific Antigen , Prostatic Hyperplasia , Prostatitis , Platelet Membrane Glycoproteins , Biomarkers, TumorABSTRACT
Immune-based therapies have experienced a pronounced breakthrough in the past decades as they acquired multiple US Food and Drug Administration (FDA) approvals for various indications. To date, six chimeric antigen receptor T cell (CAR-T) therapies have been permitted for the treatment of certain patients with relapsed/refractory hematologic malignancies. However, several clinical trials of solid tumor CAR-T therapies were prematurely terminated, or they reported life-threatening treatment-related damages to healthy tissues. The simultaneous expression of target antigens by healthy organs and tumor cells is partly responsible for such toxicities. Alongside targeting tumor-specific antigens, targeting the aberrantly glycosylated glycoforms of tumor-associated antigens can also minimize the off-tumor effects of CAR-T therapies. Tn, T, and sialyl-Tn antigens have been reported to be involved in tumor progression and metastasis, and their expression results from the dysregulation of a series of glycosyltransferases and the endoplasmic reticulum protein chaperone, Cosmc. Moreover, these glycoforms have been associated with various types of cancers, including prostate, breast, colon, gastric, and lung cancers. Here, we discuss how underglycosylated antigens emerge and then detail the latest advances in the development of CAR-T-based immunotherapies that target some of such antigens.
Subject(s)
Antigens, Neoplasm/chemistry , Biomarkers, Tumor/metabolism , Glycosylation , Hematologic Neoplasms/drug therapy , Humans , Immunotherapy, Adoptive/methods , Male , Neoplasm Recurrence, Local/metabolism , Receptors, Chimeric Antigen , T-Lymphocytes , United StatesABSTRACT
The incidence and mortality rates of gastrointestinal (GI) cancer remain high. Despite constant improvements in diagnostic and therapeutic techniques, the early diagnosis, mid- and late-stage treatment, drug tolerance, and cancer recurrence and metastasis in GI cancer remain challenging. In this review article we summarize the recent research advance in the roles of keratins in GI cancer, with the hope that they will become efficient biomarkers for the prediction, diagnosis, or treatment of these malignancies.
Subject(s)
Biomarkers, Tumor , Gastrointestinal Neoplasms/therapy , Humans , KeratinsABSTRACT
Autophagy is a programmed cell degradation process that is involved in a variety of physiological and pathological processes including malignant tumors. Abnormal induction of autophagy plays a key role in the development of hepatocellular carcinoma (HCC). We established a prognosis prediction model for hepatocellular carcinoma based on autophagy related genes. Two hundred and four differentially expressed autophagy related genes and basic information and clinical characteristics of 377 registered hepatocellular carcinoma patients were retrieved from the cancer genome atlas database. Cox risk regression analysis was used to identify autophagy-related genes associated with survival, and a prognostic model was constructed based on this. A total of 64 differentially expressed autophagy related genes were identified in hepatocellular carcinoma patients. Five risk factors related to the prognosis of hepatocellular carcinoma patients were determined by univariate and multivariate Cox regression analysis, including TMEM74, BIRC5, SQSTM1, CAPN10 and HSPB8. Age, gender, tumor grade and stage, and risk score were included as variables in multivariate Cox regression analysis. The results showed that risk score was an independent prognostic risk factor for patients with hepatocellular carcinoma ( HR = 1.475, 95% CI = 1.280-1.699, P < 0.001). In addition, the area under the curve of the prognostic risk model was 0.739, indicating that the model had a high accuracy in predicting the prognosis of hepatocellular carcinoma. The results suggest that the new prognostic risk model for hepatocellular carcinoma, established by combining the molecular characteristics and clinical parameters of patients, can effectively predict the prognosis of patients.
Subject(s)
Autophagy/genetics , Biomarkers, Tumor/genetics , Carcinoma, Hepatocellular/pathology , Humans , Liver Neoplasms/pathology , Membrane Proteins/genetics , PrognosisABSTRACT
Hepatocellular carcinoma (HCC), which makes up the majority of liver cancer, is induced by the infection of hepatitis B/C virus. Biomarkers are needed to facilitate the early detection of HCC, which is often diagnosed too late for effective therapy. The tRNA-derived small RNAs (tsRNAs) play vital roles in tumorigenesis and are stable in circulation. However, the diagnostic values and biological functions of circulating tsRNAs, especially for HCC, are still unknown. In this study, we first utilized RNA sequencing followed by quantitative reverse-transcription PCR to analyze tsRNA signatures in HCC serum. We identified tRF-Gln-TTG-006, which was remarkably upregulated in HCC serum (training cohort: 24 HCC patients vs. 24 healthy controls). In the validation stage, we found that tRF-Gln-TTG-006 signature could distinguish HCC cases from healthy subjects with high sensitivity (80.4%) and specificity (79.4%) even in the early stage (Stage I: sensitivity, 79.0%; specificity, 74.8%; 155 healthy controls vs. 153 HCC patients from two cohorts). Moreover, in vitro studies indicated that circulating tRF-Gln-TTG-006 was released from tumor cells, and its biological function was predicted by bioinformatics assay and validated by colony formation and apoptosis assays. In summary, our study demonstrated that serum tsRNA signature may serve as a novel biomarker of HCC.
Subject(s)
Biomarkers , Biomarkers, Tumor/genetics , Carcinoma, Hepatocellular/diagnosis , Hepatitis B virus , Humans , Liver Neoplasms/diagnosis , RNA, Transfer/geneticsABSTRACT
Cancer imposes a severe threat to people's health and lives, thus pressing a huge medical and economic burden on individuals and communities. Therefore, early diagnosis of cancer is indispensable in the timely prevention and effective treatment for patients. Exosome has recently become an attractive cancer biomarker in noninvasive early diagnosis because of the unique physiology and pathology functions, which reflects remarkable information regarding the cancer microenvironment, and plays an important role in the occurrence and evolution of cancer. Meanwhile, biosensors have gained great attention for the detection of exosomes due to their superior properties, such as convenient operation, real-time readout, high sensitivity, and remarkable specificity, suggesting promising biomedical applications in the early diagnosis of cancer. In this review, the latest advances of biosensors regarding the assay of exosomes were summarized, and the superiorities of exosomes as markers for the early diagnosis of cancer were evaluated. Moreover, the recent challenges and further opportunities of developing effective biosensors for the early diagnosis of cancer were discussed.
Subject(s)
Biomarkers, Tumor , Biosensing Techniques , Early Detection of Cancer , Exosomes/pathology , Humans , Neoplasms/pathology , Tumor MicroenvironmentABSTRACT
Head and neck squamous cell carcinoma (HNSCC), as the most common type (>90%) of head and neck cancer, includes various epithelial malignancies that arise in the nasal cavity, oral cavity, pharynx, and larynx. In 2020, approximately 878 000 new cases and 444 000 deaths linked to HNSCC occurred worldwide (Sung et al., 2021). Due to the associated frequent recurrence and metastasis, HNSCC patients have poor prognosis with a five-year survival rate of 40%-50% (Jou and Hess, 2017). Therefore, novel prognostic biomarkers need to be developed to identify high-risk HNSCC patients and improve their disease outcomes.
Subject(s)
Biomarkers, Tumor/genetics , Head and Neck Neoplasms/genetics , Humans , Kaplan-Meier Estimate , RNA , Squamous Cell Carcinoma of Head and Neck , Survival Analysis , Survival RateABSTRACT
Pseudomyogenic hemangioendothelioma (PHE) is a rare angiogenic tumor. Histologically, the morphological characteristics of neoplastic vessels and endothelial differentiation are not obvious, and it is easy to be confused with epithelioid sarcoma, epithelioid hemangioendothelioma and myogenic tumor. PHE usually occurs in arms and legs in young people and has a significant male predominance. The tumor has a predilection for the distal extremities and its typical manifestation is multiple center invasion of a single limb, which can involve all layers of skin and subcutaneous tissues,and is often accompanied by abvious pain. Histologically, PHE is characterized by infiltrative growth of tumor. Most tumor lesions are composed of sheets and loose fascicles of plump spindle or epithelioid cells within a background of variably prominent inflammatory infiltration, which was commonly composed of neutrophils. Some cells may resemble rhabdomyoblasts, and nuclear atypia and mitosis were rare. The tumor cells generally expressed positive cytokeratin (CK), ETS-related gene (ERG), Friend leukemia virus integration 1 (FLI1) and integrase interactor 1(INI1). In some cases, the tumor cells expressed CD31. A case of a young woman was reported in this paper, who presented with a subcutaneous mass with severe pain and was chronologically misdiagnosed with herpes zoster, low-grade malignant fibrous histiocytoma and epithelioid hemangioendothelioma. In this study, the clinical and pathological features, differential diagnosis and the latest progress in therapy of PHE were analyzed based on relevant literature.
Subject(s)
Adolescent , Adult , Biomarkers, Tumor , Child , Diagnosis, Differential , Diagnostic Errors , Female , Hemangioendothelioma, Epithelioid/pathology , Hemangioma , Histiocytoma, Malignant Fibrous/diagnosis , Humans , Male , Pain , Precancerous Conditions/diagnosisABSTRACT
BACKGROUND@#The expression of programmed cell death ligand 1 (PD-L1) as a biomarker for immunotherapy in non-small cell lung cancer (NSCLC) is routinely detected in clinical pathology department. However, the spatial heterogeneity of PD-L1 expression in intrapulmonary tumors and extrapulmonary metastases is still a challenge for the clinical testing. This study aims to explore the differences of PD-L1 expression in test samples obtaining from different sites of NSCLC. This study may contribute to the detection strategy of PD-L1 in patients with advanced lung cancer.@*METHODS@#One hundred and thirty-one cases of consecutively detected PD-L1 (22c3 assay, Dako) staining in metastatic NSCLC and 972 cases of non-paired intrapulmonary NSCLC were collected. The discrepancies of tumor proportion score (TPS) of PD-L1 expression in intrapulmonary samples and extrapulmonary metastatic samples of different sites were compared.@*RESULTS@#The positive expression rate of PD-L1 in extrapulmonary metastatic NSCLC (TPS ≥ 1%) was 61.83%, and the TPS was significantly higher than that in intrapulmonary tumors (P=0.03). The PD-L1 scores of the specimens obtained from different sites were significantly different (P=0.007). The positive rates of PD-L1 in liver and adrenal metastases were 85.71% and 77.78% respectively, and their TPS were significantly higher than that of the intrapulmonary samples (P<0.05). The positive rates of PD-L1 in lymph node, bone, brain, soft tissue, and pleural metastases was 40.00%-66.67%, with no significant differences compared to intrapulmonary tumors. The analysis of histological subtype and sample type showed that the PD-L1 score of extrapulmonary samples of adenocarcinoma subtype or surgical specimen was significantly higher than that of intrapulmonary tumors. The analysis of clinicopathological parameters showed that the PD-L1 positive expression or high expression were significantly correlated with male patients, smoking history, and epidermal growth factor receptor (EGFR) wild type.@*CONCLUSIONS@#The expression of PD-L1 in metastatic NSCLC is generally higher than that in intrapulmonary tumor, and the positive rate of PD-L1 expression was discrepant in different sites of specimen. The differences of PD-L1 score between extrapulmonary metastatic samples and intrapulmonary samples may be associated with different metastatic sites, histological subtype, and specimen type.
Subject(s)
B7-H1 Antigen/metabolism , Biomarkers, Tumor/metabolism , Carcinoma, Non-Small-Cell Lung/drug therapy , Humans , Immunohistochemistry , Lung Neoplasms/drug therapy , MaleABSTRACT
Lung cancer is one of the most prevalent malignancies with the highest morbidity and mortality rates worldwide. In recent years, with the development of immune-oncology research and several therapeutic antibodies have reach the clinic, many breakthroughs have been made in immunotherapy. The advent of immunotherapy has revolutionized the treatment of NSCLC, but the response and durable clinical benefit are only observed in a small subset of patients. Therefore, strategies to screen the potential beneficial population and improve the efficacy of immunotherapy remain an essential topic. In the current article, the author review the biomarkers that have potential to better predict responders to immunotherapy and to provide ideas for the clinical application of immunotherapy. .