Fases del desarrollo de biomarcadores para la detección temprana del cáncer / Phases of the development of biomarkers for early detection of cancer

Introducción. Un biomarcador se define como una alteración molecular presente en el desarrollo de la patogénesis del cáncer, que puede ser utilizada para el diagnóstico temprano de la enfermedad. La medición del biomarcador se hace por medio de diversas técnicas, como bioquímica, inmunohistoquímica o biología molecular, en diferentes tipos de muestras, como tejido, sangre periférica y orina. El biomarcador ideal será aquel que sea válido y específico a la vez, que sea no invasivo, barato y fácilmente detectable. El uso de biomarcadores para la detección temprana del cáncer debe seguir un desarrollo ordenado y sistemático antes de introducirlos en la práctica clínica. Métodos. Se realizó una búsqueda exhaustiva en las bases de datos de PubMed y Embase, seleccionando los artículos pertinentes para revisarlos acorde a la temática específica de interés. Resultados. Se propone la sistematización del desarrollo de biomarcadores en cinco grandes fases, las cuales tienen la característica de ser ordenadas desde las evidencias más tempranas hasta las fases finales de su estudio. Conclusiones. El correcto desarrollo de biomarcadores hace posible la introducción de intervenciones terapéuticas en el ámbito de la prevención secundaria del cáncer.

Introduction. A biomarker can be defined as a molecular alteration present in the development of cancer pathogenesis which can be used for early diagnosis of the disease. The measurement of the biomarker can be carried out through various techniques such as biochemistry, immunohistochemistry, molecular biology, in different types of samples such as tissue, peripheral blood, and urine. The ideal biomarker will be one that is valid and specific while is non-invasive, cheap, and easily detectable. The use of biomarkers for the early detection of cancer must follow an orderly and systematic development before introducing them into clinical practice. Methods. An exhaustive search was performed in PubMed and Embase databases, selecting the relevant articles according to the specific topic of interest. Results. Systematization of the development of biomarkers in five large phases is proposed, which has the characteristic of being ordered from the earliest evidence to the final phases of their study. Conclusions. The correct development of biomarkers makes possible the introduction of therapeutic interventions in the field of secondary prevention of cancer.

Cistoadenoma mucinoso biliar: Un reto diagnóstico / Mucinous biliary cystadenoma: A diagnostic challenge

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

Uterine POLE mutant endometrioid carcinoma combined with human papilloma virus-associated cervical adenocarcinoma: A case report and literature review / 北京大学学报(医学版)

Independent primary uterine and cervical adenocarcinoma are rare and difficult to identify their origins, which makes treatment decision difficult. A 46-year-old female with endometrioid carcinoma and adenocarcinoma, human papilloma virus (HPV)-associated of the uterine cervix was reported. The patient presented with increased menstrual flow, contact bleeding and watery leucorrhea for more than one year, and the imaging findings showed abnormal uterine morphology, irregular margins, and multiple abnormal signals in uterine cavity and myometrium, which suggested multiple leiomyomas of the uterus. The signal intensity in the right muscle layer was markedly enhanced, suggesting a smooth muscle tumor of uncertain malignant potential. A large number of cystic hypointensity was seen in the cervix, and multiple cysts were considered. The initial preoperative diagnosis was multiple leiomyoma of the uterus, and a hysterectomy operation was planned. During the operation, the uterus was sent for frozen sections. There was a mass in the endometrium of the fundus, with a soft grayish-red cut surface and a clear border with the myometrium, and there was a grayish-white nodule in the cervix with a hard grayish-white cut surface. The two masses were well demarcated from each other, and the distance between them was 30 mm. The result of the frozen sections indicated the malignant tumor of the endometrium, and the extended hysterectomy+pelvic lymphadenectomy+partial resection of the greater omentum was performed. After the operation, the paraffin sections were sent to the Department of Pathology of the Peking University Third Hospital for histochemistry, POLE gene sequencing and HPV RNAscope tests, and the final diagnosis was a synchronous endometrioid carcinoma (POLE-mutant according to the WHO classification) and an adenocarcinoma, HPV-associated of the uterine cervix. Now the patient had been treated with 2 cycles of chemotherapy and her condition was fine. Through the analysis of the histological, immunohistochemical and molecular detection results of this case, the importance of applying HPV RNAscope and TCGA molecular typing in the diagnosis of cervical adenocarcinomas and endometrial carcinomas was emphasized. At the same time, gynecologists should not blindly rely on intraoperative frozen sections, and should pay attention to preoperative pathological examination, and make appropriate operation methods according to the results in order to prevent passivity in the surgery.

Tumor markers expression levels in gastric cancer patient's peripheral blood by rt-pcr assessment / Avaliação por rt-pcr de expressão de marcadores tumorais em sangue periférico de pacientes com câncer gástrico

ABSTRACT BACKGROUND: Hematological recurrence is the second most frequent cause of failure in the treatment of gastric cancer. The detection of circulating tumor markers in peripheral blood by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) method may be a useful tool to predict recurrence and determine the patient's prognosis. However, no consensus has been reached regarding the association between the tumor markers level in peripheral blood and its impact on patient survival. AIMS: To evaluate the expression of the circulating tumor markers CK20 and MUC1 in peripheral blood samples from patients with gastric cancer by qRT-PCR, and to verify the association of their expression levels with clinicopathological characteristics and survival. METHODS: A total of 31 patients with gastric adenocarcinoma were prospectively included in this study. CK20 and MUC1 expression levels were analyzed from peripheral blood by the qRT-PCR technique. RESULTS: There was no statistically significant (p>0.05) association between CK20 expression levels and clinical, pathological, and surgical features. Higher MUC1 expression levels were associated with female patients (p=0.01). There was a correlation between both gene levels (R=0.81, p<0.001), and CK20 level and tumor size (R=0.39, p=0.034). CONCLUSIONS: CK20 and MUC1 expression levels could be assessed by qRT-PCR from total peripheral blood samples of patients with gastric cancer. CK20 levels were correlated to MUC1 levels as well as to tumor size. There was no difference in disease-free survival and overall survival regarding both genetic markers expression in this series.

RESUMO RACIONAL: A recorrência hematológica é a segunda causa mais frequente de falha no tratamento do câncer gástrico. A detecção de marcadores tumorais circulantes no sangue periférico, pelo método de reação em cadeia da polimerase de transcrição reversa quantitativa (qRT-PCR) pode ser uma ferramenta útil para prever a recorrência e determinar o prognóstico do paciente. No entanto, ainda não foi alcançado consenso em relação à associação entre o nível de marcadores tumorais circulantes no sangue periférico e seu impacto na sobrevida do paciente. OBJETIVOS: Avaliar a expressão de CK20 e MUC1 em amostras de sangue periférico de pacientes com câncer gástrico por meio de qRT-PCR e verificar a associação dos níveis de expressão com características clinicopatológicas e sobrevida. MÉTODOS: Trinta e um pacientes com adenocarcinoma gástrico foram incluídos, prospectivamente. Os níveis de expressão de CK20 e MUC1 foram analisados a partir de sangue periférico por meio de qRT-PCR. RESULTADOS: Não houve associação estatisticamente significativa (p>0,05) entre os níveis de expressão de CK20 com características clínicas, patológicas e cirúrgicas. Níveis mais elevados de expressão de MUC1 estavam associados a pacientes do sexo feminino (p=0,01). Houve correlação entre os níveis de ambos os genes (R=0,81, p<0,001), nível de CK20 e tamanho do tumor (R=0,39, p=0,034). CONCLUSÕES: Os níveis de CK20 e MUC1 podem ser avaliados por qRT-PCR a partir de amostras de sangue periférico total de pacientes com câncer gástrico, os níveis de CK20 estavam correlacionados com os de MUC1, assim como tamanho do tumor. Não houve diferença de sobrevida global ou livre de doença em relação à expressão de ambos marcadores genéticos nesta série.

Recentes avanços em biomarcadores para diagnóstico, prognóstico e avaliação terapêutica no câncer cervical / Recent advances in biomarkers for diagnosis, prognosis, and therapeutic evaluation in cervical cancer

Objetivos: revisar os estudos clínicos acerca de biomarcadores para o câncer cervical publicados nos últimos 10 anos, com foco no diagnóstico, prognóstico e avaliação do tratamento. Metodologia: as bases de dados PubMed, Web of Science e Science Direct foram pesquisadas utilizando os descritores "Uterine Cervical Neoplasms" e "Biomarkers". Foram selecionados os artigos originais publicados em inglês ou português, no período de 2011 a 2021. Após uma triagem pelos títulos e resumos dos artigos, aqueles relacionados ao objetivo do estudo foram lidos integralmente para a decisão final de inclusão na revisão. Os trabalhos que atenderam todos os critérios de seleção tiveram seus dados extraídos, principalmente, no que se refere ao tipo e objetivo do biomarcador proposto, população do estudo, tamanho da amostra, metodologia utilizada e principais desfechos obtidos. Resultados: esta estratégia de busca e seleção resultou em 22 artigos publicados nos últimos 10 anos na temática de interesse. Ocorreu um grande empenho na investigação de biomarcadores séricos para o câncer cervical, com a vantagem de serem minimamente invasivos. Houve destaque para marcadores genéticos e moleculares, como aqueles voltados para a metilação do DNA, detecção de polimorfismos, padrões de expressão de micro-RNA e expressão de genes relacionados à proliferação, imortalização e invasão celular. Conclusão: os dados reunidos encorajam a ampliação das pesquisas para aprimorar e validar a eficiência destes biomarcadores em grandes populações. É evidente o potencial dos biomarcadores como estratégia para melhorar o manejo do diagnóstico e o tratamento do câncer cervical, sendo que a utilização de marcadores genéticos parece ser o futuro dos biomarcadores para o câncer cervical

Aims: to review clinical studies on biomarkers for cervical cancer published in the last 10 years, focusing on the diagnosis, prognosis, and treatment evaluation. Methods: PubMed, Web of Science, and Science Direct databases were searched using the descriptors "Uterine Cervical Neoplasms" and "Biomarkers". Original articles published in English or Portuguese from 2011 to 2021 were selected. After screening by the titles and abstracts of the articles, those related to the objective of the study were read in full for the final decision of inclusion in the review. The studies that met all the selection criteria had their data extracted, especially regarding the type and objective of the biomarker proposed, study population, sample size, methodology used, and main outcomes obtained. Results: this search and selection strategy resulted in 22 articles published in the last 10 years on the topic of interest. There was a great effort to investigate serum biomarkers for cervical cancer, with the advantage of being minimally invasive. There was an emphasis on genetic and molecular markers, such as those focused on DNA methylation, detection of polymorphisms, expression patterns of microRNA, and expression of genes related to cell proliferation, immortalization, and invasion.Conclusions: the data gathered encourage expanded research to improve and validate the efficiency of these biomarkers in large populations. The potential of biomarkers as a strategy to improve the management of cervical cancer diagnosis and treatment is evident, and the use of genetic markers appears to be the future of biomarkers for cervical cancer

Can TILs be associated with prognostic factors and survival rates in breast cancer? A retrospective analysis

Introduction: The relationship between the tumor inflammatory infiltrate, also known as tumor-infiltrating lymphocytes (TILs), and invasive breast carcinomas has been extensively studied in recent years to verify its association with prognosis and response to treatment. The goal of this study was to associate the presence of TILs with patient's survival time. Methods: We studied prognostic clinicopathological characteristics already established in the literature and their impact on overall five-year survival time of patients with invasive breast cancer treated at Hospital Santa Casa in Belo Horizonte, Minas Gerais, Brazil, in 2011 (n=290). This was an observational and retrospective study. Results: The presence of TILs was associated with tumors of no special type (p=0.018) and with younger age of the patients (p=0.042). Smaller tumor size (HR: 19.24; 95%CI 4.30­86.15; p<0.001), absence of metastasis to the axillary lymph nodes (HR: 2.80; 95%CI 1.02­7.70; p=0.002), positivity for progesterone receptor (HR: 0.39; 95%CI 0.17­0.87; p=0.022), and presence of TILs (HR: 0.23; 95%CI 0.08­0.65; p=0.005) were associated with longer survival times. Conclusions: This study suggests that the presence of TILs, along with other clinicopathological characteristics, is a prognostic factor in breast cancer

Research progress of SMIM1 in Vel blood type, tumor and plasmodium infection / 中国输血杂志

Small integral membrane protein 1(SMIM1) gene encodes Vel blood group antigen, and homozygous deletion of 17 bases pairs in its exon 3 leads to Vel negative phenotype. As a rare phenotype, accurate identification and prevention of transfusion reaction for Vel negative phenotype is particularly important. In addition to serving as a Vel blood group antigen, recent bioinformatics analysis suggests that SMIM1 protein may be a new tumor biomarker involved in the occurrence and development of numerous tumors. Due to the similarity in structure between SMIM1 protein and glycoprotein, and its phosphorylation in red blood cells infected with Plasmodium falciparum, it is speculated that SMIM1 protein may be involved in the development of malaria. Therefore, this article provides a review of the related research on SMIM1 and its coding protein in Vel blood type, tumor and plasmodium infection.

BRCA mutations: Implications of genetic testing in ovarian Cancer

Ovarian cancer (OC) is one of the most lethal gynecological cancers with a 5?year survival rate that ranges from 30% to 40%. Breast cancer genes (BRCA1 and BRCA2) play a key role in maintaining genomic stability. Mutations in BRCA1/2 genes lead to the accumulation of double?strand breaks, resulting in tumorigenesis. The risk of developing OC in women with BRCA1 and BRCA2 mutations is 39% and 11%, respectively, by 70 years of age. BRCA1/2 mutation testing is thus important to identify women at greatest risk of developing OC in addition to its impact on diagnosis, prognosis, and targeted therapy. Genetic testing is required to identify the BRCA mutations and thus select patients who can benefit from polyadenosine diphosphate (ADP)杛ibose polymerase (PARP) inhibitor therapy. Tumor BRCA mutation testing can detect both germline and somatic mutations allowing implementation of preventive strategies on a broader population. Various international guidelines recommend BRCA1/2 mutation genetic testing in all OC patients irrespective of age and family history. This review focuses on the role of BRCA mutation testing in OC

Expressão do RNAm e metilação do DNA do gene DKK2 em câncer colorretal / Rnam expression and dna methylation of dkk2 gene in colorectal câncer

ABSTRACT BACKGROUND: Colorectal cancer is the third most common neoplasm in the world. Methylation of tumor related genes in CpG islands can cause gene silencing and been involved in the development of cancer. The potential role of DKK2 as a biomarker for early diagnosis of colorectal cancer remains unclear. OBJECTIVE: The aim of the study was to evaluate the profile of methylation and RNAm expression of DKK2 as potential predictors of colorectal cancer diagnosis and prognosis. METHODS: Expression of mRNAs encoding DKK2 in 35 colorectal cancer tissues was quantified using real-time polymerase chain reaction analysis. The DNA methylation was studied by high resolution melting analysis. The general characteristics of the patients were collected. DKK2 methylation and expression were compared to clinical, pathological aspects and overall survival. RESULTS: Among the 35 patients studied, 18 were male, 10 were on right colon and 25 on left colon. Among the 20 patients with high hypermethylation, 15 of them had mRNA low expression of DKK2. There was no significant association between DKK2 promoter methylation and mRNA DKK2 expression and clinical or pathological features. DKK2 promoter methylation (P=0.154) and DKK2 RNA expression (P=0.345) did not show significant correlation with overall survival. CONCLUSION: DKK2 promoter methylation and DKK2 RNA status appear to be biomarkers of cancer diagnosis but not predictors of prognosis.

RESUMO CONTEXTO: O câncer colorretal é a terceira neoplasia mais comum no mundo. A metilação de alguns genes nas ilhas CpG podem causar silenciamento gênico e estar envolvida no desenvolvimento de câncer. O potencial papel de DKK2 como um biomarcador no diagnóstico precoce de CCR permanece incerto. OBJETIVO: O objetivo do estudo foi avaliar o perfil de metilação e expressão de RNAm do gene DKK2 para identificar preditores potenciais de diagnóstico e prognóstico de CCR. MÉTODOS: A expressão de mRNAs que codificam DKK2 em 35 tecidos de câncer colorretal foi quantificada por reação em cadeia da polimerase em tempo real e a metilação do DNA foi verificada por análise de alta resolução. As características gerais dos pacientes foram coletadas. A metilação e expressão de DKK2 foram comparadas aos aspectos clínicos, patológicos e à sobrevida global. RESULTADOS: Entre os 35 pacientes estudados, 18 eram do sexo masculino, 10 tumores eram do cólon ascendente ou transverso e 25 do descendente ou reto. Entre os 20 pacientes com hipermetilação, 12 deles apresentaram baixa expressão de RNAm do gene DKK2. Não houve associação significativa entre a metilação do promotor de DKK2 e a expressão de RNAm de DKK2 e características clínicas ou patológicas. A metilação do promotor de DKK2 e a expressão do RNA de DKK2 não mostraram correlação com sobrevida global dos pacientes com CCR. CONCLUSÃO: A metilação do gene promotor e a expressão do RNAm do gene DKK2 parecem ser biomarcadores de diagnóstico de câncer, mas não se mostraram úteis na avaliação prognóstica.

Variación de los biomarcadores tumorales en pacientes con enfermedades respiratorias crónicas / Variation of tumoral biomarkers in patients with chronic respiratory diseases

Introducción: Los biomarcadores son sustancias biológicas o bioquímicas que aparecen como respuesta del organismo ante ciertos tipos de tumores y que reflejan la etapa y el grado de estos. Objetivo: Determinar la asociación de los marcadores tumorales con los procesos respiratorios crónicos. Métodos: Se realizó un estudio descriptivo y transversal de 306 pacientes diagnosticados con enfermedades respiratorias crónicas, atendidos en las consultas comunitarias de neumología de la provincia de Santiago de Cuba, de enero del 2014 a diciembre del 2018. Resultados: En la serie predominaron el sexo masculino y las edades de 60 a 69 años, así como las enfermedades intersticiales, la bronquitis crónica y la enfermedad pulmonar obstructiva crónica. De igual modo, resultaron importantes los estudios radiológicos para la detección de procesos neoplásicos, sobre todo el empleo de la tomografía axial computarizada. Por otra parte, los marcadores que presentaron valores alterados fueron el CYFRA 21.1 y el CA 72.4, de manera que se demostró su asociación con los procesos respiratorios crónicos. Conclusiones: Los biomarcadores tumorales son una herramienta útil en el seguimiento de pacientes con neoplasias malignas, pero también muestran valores alterados ante la presencia de varias enfermedades respiratorias crónicas sin que ello represente la existencia de un proceso maligno.

Introduction: Biomarkers are biological or biochemical substances which emerge as a response of the organism on certain types of tumors and which reflect the stage or degree of them. Objective: To determine the association of tumoral markers with the chronic respiratory events. Methods: A descriptive and cross-sectional study of 306 patients diagnosed with chonic respiratory diseases and assisted at the Pneumology community outpàtients from Santiago de Cuba province was carried out from January, 2014 to December, 2018. Results: Male sex and ages between 60 o 69 years as well as interstitial diseases, chronic bronchitis and the chronic obstructive pulmonary disease predominated in the series. Likewise, radiological studies were also important for detecting neoplasic processes, mainly with the use of the axial computerized tomography. On the other side, markers presenting altered values were the CYFRA 21.1 y el CA 72.4, so that its association with the chronic respiratory processes. Conclusions: Tumoral biomarkers are an usefull tool in the follow-up of patients with malignant neoplasies, but also they show altered values in the presence of different chronic respiratory diseases, which doesn´t mean there is a malignant process.

Bazo metastásico de un adenocarcinoma de endometrio. Presentación de un caso / Splenic metastasis from endometrial adenocarcinoma. A case presentation

Introducción: La metástasis esplénica de un carcinoma endometrial es un acontecimiento clínico raro, con solo 13 casos documentados en la literatura, revisada. La evolución de esta metástasis, en una paciente atendida, en nuestra Institución, fue el motivo para publicar este trabajo. Hay otras enfermedades oncológicas que en su evolución de progresión o recaída cursan con este tipo de cuadro clínico donde el tratamiento quirúrgico es fundamental y así complementar con tratamiento de quimioterapia. Se hizo una revisión en publicaciones cubanas no se encontró reporte del tema. Objetivo: Presentar un caso con un adenocarcinoma de endometrio tipo endometroide que metastiza al bazo con histología de células claras. Presentación: Paciente de 45 años, con diagnóstico de adenocarcinoma de endometrio con estadiamiento quirúrgico pT3A Nx Mo etapa IIIA Grado 2; este estadiamiento es el anterior a 2009, llevó su tratamiento quirúrgico y radioterapia complementaria, controlada por 21 meses. En consulta de seguimiento se diagnostica metástasis al bazo, por lo que se realiza esplenectomía y es tratada con quimioterapia; fue atendida por el equipo multidisciplinario de ginecología oncológica; las investigaciones realizadas estuvieron basadas en inmuhistoquimica, imageneología y tratamiento de soporte cuando lo necesitó. Conclusiones: La metástasis esplénica por un cáncer de endometrio es rara, es el primero reportado en Cuba, los estudios inmuhistoquímicos y de imágenes son fundamentales(AU)

Introduction: Splenic metastasis from endometrial carcinoma is a rare clinical event with only 13 documented cases in the literature reviewed. The evolution of a patient with this metastasis attended in our institution was the reason that motivated us to publish this work. There are other oncological diseases that are accompanied by this clinical picture during their evolution of progression where surgical treatment complemented with chemotherapy treatment is essential. A literature review was carried out in Cuban publications, but no reports on the topic were found. Objective: The aim of this work is to present an endometroid type case endometrium adenocarcinoma which metastasizes to the spleen with clear cell histology. Case presentation: Forty-five-year-old patient with diagnosis of endometrium adenocarcinoma with surgical stage pT3a Nx Mo stage IIIA Grade 2; this quantification was defined before 2009. The patient underwent surgical treatment which was complemented with radiotherapy and then followed for 21 months. In the follow-up consultation, spleen metastasis was diagnosed; so she underwent splenectomy and was treated with chemotherapy. She was treated by the multidisciplinary gynecologic oncology team; the investigations performed were based on immuhistochemistry, imaging, and supportive treatment whenever needed. Conclusions: Splenic metastasis from endometrial cancer is rare; it is the first case reported in Cuba. Immuhistochemical and imaging studies are essential(AU)

Análise dos efeitos biológicos associados ao fator de choque térmico 1 (HSF1) no carcinoma de células escamosas oral / Analysis of the biological effects associated with heat shock factor 1 (HSF1) in oral squamous cell carcinoma

O carcinoma de células escamosas oral exibe altas taxas de morbimortalidade e evidências em vários tipos tumorais mostram que processos associados à iniciação, à progressão e à resistência terapêutica são regulados por HSF1. Portanto, esclarecer as vias de participação de HSF1 no câncer oral pode auxiliar no entendimento do seu comportamento biológico. Em uma pesquisa previamente desenvolvida por nosso grupo, foram realizados a análise clinicopatológica e o estudo da imunoexpressão de HSF1 em 70 casos de carcinoma de células escamosas de língua oral (CCELO) em comparação com 30 espécimes de mucosa oral normal (MON). Nesta atual investigação, avaliou-se a participação de HSF1 na tumorigênese do CCELO, através de experimentos in vitro com a linhagem celular SCC15, silenciada e não silenciada, com silenciamento confirmado por qRT-PCR e Western Blot. Foram analisadas a viabilidade e proliferação celular, (CellTiter e BRDU, respectivamente), influência no ciclo celular (iodeto de propideo e análise por citometria de fluxo), capacidade de invasão (sistema transwell/Matrigel)e transição epitélio-mesenquimal (TEM) (expressão de E-caderina e vimentina por qRT-PCR). Nossos resultados anteriores evidenciaram que quanto aos casos de CCELO, 57,1% exibiram estadiamento clínico III ou IV, 82,9% foram gradados como de alto grau segundo Bryne (1998), 47,1% como de alto risco segundo Brandwein-Gensler et al. (2005) e 58,8% como de alto risco de acordo com o modelo BD. Observou-se repercussão da gradação de Bryne (1998) (p= 0,05) na sobrevida livre de doença. Tamanho do tumor T3 ou T4 (p= 0,04), recidiva local (p= 0,02) e modelo BD (p=0,02) repercutiram na sobrevida global. Encontrou-se previamente resultado significativo (p<0,01) quando se comparou a imunoexpressão de HSF1 entre a MON e o CCELO, sem associações significativas da imunoexpressão com os parâmetros clinicopatológicos. A partir dos estudos funcionais, observou-se que HSF1 é superexpresso na linhagem SCC15 comparada aos queratinócitos imortalizados (p<0,005) e que o silenciamento deste gene inibiu a proliferação celular (p< 0,005), avanço nas fases do ciclo celular, com aumento do número de células nas fases G0/G1 (p<0,01) e redução das células na fase S (p<0,001), capacidade de invasão (p<0,05) e TEM, com diminuição da expressão de vimentina (p<0,001) e aumento de E-caderina (p<0,05), quando comparadas as linhagens silenciada e controle. Diante destes resultados, sugere-se que HSF1 pode desempenhar diversas funções que ajudam a manter a estabilidade celular em meio às condições estressoras do microambiente tumoral. Assim, futuramente, estratégias envolvendo sua regulação pode ser uma terapia útil no controle da progressão do câncer oral (AU).

Oral squamous cell carcinoma exhibits high rates of morbimortality and evidence in several tumor types shows that processes associated with initiation, progression and therapeutic resistance are regulated by HSF1. Therefore, to clarify the pathways of HSF1 participation in the oral cancer may help in the understanding of its biological behavior. In research previously developed by our group, a clinicopathological analysis and an immunoexpression study of HSF1 of 70 cases of oral tongue squamous cell carcinoma (OTSCC) were performed in comparison with 30 samples of the normal oral mucosa (NOM). In this current investigation, the role of HSF1 in OTSCC tumorigenesis was evaluated, through in vitro experiments with the SCC15 cell line, silenced and non-silenced, with silencing confirmed by qRT-PCR and Western Blot. Cell viability and proliferation (CellTiter and BrdU, respectively), influence on cell cycle (propidium iodide and flow cytometry analysis), invasion capacity (transwell / Matrigel system), and epithelial-mesenchymal (EMT) (expression of E-cadherin and vimentin by qRT-PCR) were evaluated. Our previous results showed that as for the cases of OTSCC, 57.1% exhibited clinical stage III or IV, 82.9% were graded as high grade according to Bryne (1998), 47.1% as high risk according to BrandweinGensler et al. (2005) and 58.8% as high risk according to the BD model. Bryne's gradation (1998) (p = 0.05) had an impact on disease-free survival. Tumor size T3 or T4 (p = 0.04), local recurrence (p = 0.02) and BD model (p = 0.02) impacted overall survival. A significant initial result (p <0.01) was found when comparing an HSF1 immunoexpression between NOM and OTSCC, with no significant association of immunoexpression with clinicopathological tests. From the functional studies, it was observed that HSF1 is overexpressed in the SCC15 cell line compared to immortalized keratinocytes (p <0.005) and that the silencing of this gene inhibited cell proliferation (p <0.005), advance in the cell cycle phases, with an increase in the number of cells in phases G0/G1 (p <0.01) and reduction of cells in phase S (p <0.001), invasion capacity (p <0.05) and EMT, with decreased vimentin expression (p <0.001) and increased E-cadherin (p <0.05), when compared to silenced and control lines. Given these results, it is suggested that HSF1 can exert a range of functions that maintain cell stability amid the stressful conditions of the tumor microenvironment. Thus, in the future, strategies involving its regulation may be a useful therapeutic tool in controlling the progress of the oral cancer (AU).

Is there a clinical pathological correlation of colorectal adenocarcinoma with the immunohistochemical expression of opn and abcb5? / Há correlação clínicopatológica do adenocarcinoma colorretal com a expressão imunoistoquímica do opn e abcb5?

ABSTRACT Background: Studies with biomarkers in TMA (tissue microarray) have been showing important results regarding its expression in colon cancer. Aim: Correlate the expression profile of the OPN and ABCB5 biomarkers with the epidemiological and clinicopathological characteristics of the patients, the impact on the progression of the disease and the death. Method: A total of 122 CRC patients who underwent surgical resection, immunomarking and their relationship with progression and death events were evaluated. Result: The average age was 61.9 (±13.4) years. The cases were distributed in 42 (35.9%) in the ascending/transverse colon, 31 (26.5%) in the sigmoid, 27 in the rectum (23.1%), 17 (14.5%) in the descending colon. Most patients had advanced disease (stages III and IV) in 74 cases (60.9%). There was a predominance of moderately differentiated tumors in 101 samples (82.8%); despite this, the poorly differentiated subtype proved to be an independent risk factor for death in 70%. Metastasis to the liver proved to be an independent risk factor for death in 75% (18/24), as well as patients with primary rectal tumors in 81.5% (22/27). Conclusion: The immunohistochemical expression of the OPN and ABCB5 markers was not associated with epidemiological and clinicopathological characteristics. Regarding the progression of disease and death, it was not possible to observe a correspondence relationship with the evaluated markers.

RESUMO Racional: Estudos com biomarcadores com TMA (tissue microarray) vêm demostrando resultados importantes em relação à expressão de biomarcadores em câncer de cólon. Objetivo: Correlacionar o perfil de expressão dos biomarcadores OPN e ABCB5 com as características epidemiológicas e clinicopatológicas dos pacientes, o impacto na progressão de doença e no evento óbito. Método: Foram avaliados 122 pacientes de CCR submetidos à ressecção cirúrgica e à imunomarcação e relação com os eventos progressão e óbito. Resultado: A média de idade encontrada foi de 61,9 (±13,4) anos. Os casos distribuíram-se em 42 (35,9%) no cólon ascendente/transverso, 31 (26,5%) no sigmoide, 27 no reto (23,1%), 17 (14,5%) no cólon descendente. A maioria dos pacientes apresentou doença avançada (estadio III e IV) em 74 casos (60,9%). Houve predomínio de tumor moderadamente diferenciado em 101 amostras (82,8%); apesar disso, o subtipo pouco diferenciado mostrou-se como fator de risco independente para óbito em 70% dos casos. Metástase para o fígado mostrou-se fator de risco independente para óbito em 75% dos casos (18/24), assim como pacientes com tumores primários de reto em 81,5% (22/27). Conclusão: A expressão imunoistoquímica dos marcadores OPN e ABCB5 não apresentou associação com as características epidemiológicas e clinicopatológicas. Em relação à progressão de doença e evento óbito, não se conseguiu observar relação de correspondência com os marcadores avaliados.

Clinical Implementation of Precision Medicine in Gastric Cancer

Gastric cancer (GC) is one of the deadliest malignancies in the world. Currently, clinical treatment decisions are mostly made based on the extent of the tumor and its anatomy, such as tumor-node-metastasis staging. Recent advances in genome-wide molecular technology have enabled delineation of the molecular characteristics of GC. Based on this, efforts have been made to classify GC into molecular subtypes with distinct prognosis and therapeutic response. Simplified algorithms based on protein and RNA expressions have been proposed to reproduce the GC classification in the clinical field. Furthermore, a recent study established a single patient classifier (SPC) predicting the prognosis and chemotherapy response of resectable GC patients based on a 4-gene real-time polymerase chain reaction assay. GC patient stratification according to SPC will enable personalized therapeutic strategies in adjuvant settings. At the same time, patient-derived xenografts and patient-derived organoids are now emerging as novel preclinical models for the treatment of GC. These models recapitulate the complex features of the primary tumor, which is expected to facilitate both drug development and clinical therapeutic decision making. An integrated approach applying molecular patient stratification and patient-derived models in the clinical realm is considered a turning point in precision medicine in GC.

Usefulness of Carbohydrate Antigen 19-9 Test in Healthy People and Necessity of Medical Follow-up in Individuals with Elevated Carbohydrate Antigen 19-9 Level / 가정의학회지

BACKGROUND: Carbohydrate antigen 19-9 (CA 19-9) is a tumor marker whose level is elevated in many types of cancers and other benign conditions. CA 19-9 levels are frequently found to be elevated in individuals during general health examinations. This study aimed to investigate the clinical characteristics of such individuals and to determine the need for medical follow-up. METHODS: We investigated individuals who underwent a health inspection, including a serum CA 19-9 test, at our center. Their CA 19-9 levels, age, sex, body mass index (BMI), and personal and past histories were investigated. Additionally, subgroup analyses were performed for those who underwent follow-up study for the elevated CA 19-9 levels. RESULTS: Of 58,498 subjects, 581 (1.0%) had elevated CA 19-9 levels. Multivariate analyses revealed that older age, female sex, lower BMI, and diabetes were independent predisposing factors for elevated CA 19-9 level. A subgroup analysis revealed that the causative conditions were identified in 129 of 351 subjects (36.8%). Among them, the causative conditions in 31 subjects (8.8%, including four cases of cancer and 15 of benign tumors) were not detected at the initial check-up and were found during the follow-up period. CONCLUSION: The use of CA 19-9 as a marker for cancer in healthy individuals is inappropriate. However, medical follow-up in individuals with elevated CA 19-9 levels may be useful because some causative diseases may be detected during follow-up.

Asociación de los biomarcadores con el cáncer pulmonar en pacientes de un servicio de neumología / Association of biomarkers with lung cancer in patients of a pneumology service

Se realizó un estudio descriptivo y transversal de 199 pacientes diagnosticados con cáncer de pulmón, atendidos en el Servicio de Neumología del Hospital General Docente Dr Juan Bruno Zayas Alfonso de Santiago de Cuba, de enero del 2014 a diciembre del 2017, con vistas a determinar la asociación de los marcadores tumorales con el proceso neoplásico. En la serie predominaron el sexo masculino y las edades de 50 a 69 años, así como los estadios IIIB y IV de la enfermedad. De igual modo resultó más frecuente la localización en el pulmón derecho y el tipo histológico cáncer de pulmón células no pequeñas, del cual fue más representativo el adenocarcinoma. Por su parte, el CYFRA 21.1 y el CA 72.4 fueron los dos marcadores asociados con los procesos tumorales pulmonares y fueron ratificados como tal.

A descriptive and cross-sectional study of 199 patients diagnosed with lung cancer, assisted in the Pneumology Service of Dr Juan Bruno Zayas Alfonso Teaching General Hospital was carried out in Santiago de Cuba, from January, 2014 to December, 2017, aimed at determining the association of tumoral markers with the neoplastic process. In the series there was a prevalence of the male sex and patients aged 50 to 69, as well as the IIIB and IV stages of the disease. In a same way it was more frequent the localization in the right lung and the histologic type non small cells lung cancer, from which adenocarcinoma was more representative. On the other hand, CYFRA 21.1 and CA 72.4 were the two markers associated with lung tumoral processes and were confirmed as such.

Identification and Validation of Circulating MicroRNA Signatures for Breast Cancer Early Detection Based on Large Scale Tissue-Derived Data / 한국유방암학회지

PURPOSE: Breast cancer is the most commonly occurring cancer among women worldwide, and therefore, improved approaches for its early detection are urgently needed. As microRNAs (miRNAs) are increasingly recognized as critical regulators in tumorigenesis and possess excellent stability in plasma, this study focused on using miRNAs to develop a method for identifying noninvasive biomarkers. METHODS: To discover critical candidates, differential expression analysis was performed on tissue-originated miRNA profiles of 409 early breast cancer patients and 87 healthy controls from The Cancer Genome Atlas database. We selected candidates from the differentially expressed miRNAs and then evaluated every possible molecular signature formed by the candidates. The best signature was validated in independent serum samples from 113 early breast cancer patients and 47 healthy controls using reverse transcription quantitative real-time polymerase chain reaction. RESULTS: The miRNA candidates in our method were revealed to be associated with breast cancer according to previous studies and showed potential as useful biomarkers. When validated in independent serum samples, the area under curve of the final miRNA signature (miR-21-3p, miR-21-5p, and miR-99a-5p) was 0.895. Diagnostic sensitivity and specificity were 97.9% and 73.5%, respectively. CONCLUSION: The present study established a novel and effective method to identify biomarkers for early breast cancer. And the method, is also suitable for other cancer types. Furthermore, a combination of three miRNAs was identified as a prospective biomarker for breast cancer early detection.

Application of circulating tumor DNA in diagnosis and prognosis of epithelial ovarian cancer / 中华全科医师杂志

In the development of cancer, the DNA fragments of tumor cells enter into the blood circulation to form circulating tumor DNA (ctDNA), which is an indicator for detecting and quantifying tumor mutations. Epithelial ovarian cancer accounts for most of the histological types in ovarian cancer. This article reviews the clinical application of ctDNA in epithelial ovarian cancer, including the early diagnosis, therapeutic effect evaluation after operation and adjuvant therapy, tumor load assessment, dynamic monitoring during the follow-up and the prognosis of patients.

Screening of serum tumor biomarkers in breast cancer by proteomics / 实用医学杂志

Objective To screen tumor biomarker of breast cancer from expressed differently in breast cancer patients and health by proteomics techniques. Methods Collecting 10 serum cases of breast cancer and healthy respectively,protein spot was separated by two-dimensional electrophoresis,protein expressed differently from breast cancer and healthy was screened by PDQuest software ,and identified by mass spectrometry. Results The 2-DE maps of breast cancer and healthy were established ,22 differentially expressed proteins were analyzed by PDQuest software,took the healthy group as the reference,there were 18 spots with up-regulated serum protein, and 4 spots with down-regulated serum proteins in breast cancer group.12 protein spots were sampled and detected by mass spectrometry. Finally ,4 differentially expressed proteins were identified successfully ,the proteins were confirmed by the database,named as ankyrin-3 isoform X7,keratin,type I cytoskeletal 9,nesprin-2 isoform X11, Dynein heavy chain 10,axonemal isoform X9. Conclusion The 4 differentially expressed proteins in healthy group and breast cancer group can be potential candidate biomarkers for diagnosis of breast cancer.

Screening of serum tumor biomarkers in breast cancer by proteomics / 实用医学杂志

Objective To screen tumor biomarker of breast cancer from expressed differently in breast cancer patients and health by proteomics techniques. Methods Collecting 10 serum cases of breast cancer and healthy respectively,protein spot was separated by two-dimensional electrophoresis,protein expressed differently from breast cancer and healthy was screened by PDQuest software ,and identified by mass spectrometry. Results The 2-DE maps of breast cancer and healthy were established ,22 differentially expressed proteins were analyzed by PDQuest software,took the healthy group as the reference,there were 18 spots with up-regulated serum protein, and 4 spots with down-regulated serum proteins in breast cancer group.12 protein spots were sampled and detected by mass spectrometry. Finally ,4 differentially expressed proteins were identified successfully ,the proteins were confirmed by the database,named as ankyrin-3 isoform X7,keratin,type I cytoskeletal 9,nesprin-2 isoform X11, Dynein heavy chain 10,axonemal isoform X9. Conclusion The 4 differentially expressed proteins in healthy group and breast cancer group can be potential candidate biomarkers for diagnosis of breast cancer.