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1.
Arch. argent. pediatr ; 119(5): e487-e498, oct. 2021. tab, ilus
Article in English, Spanish | LILACS, BINACIS | ID: biblio-1292280

ABSTRACT

Si bien el carcinoma colorrectal (CCR) es la tercera enfermedad oncológica más frecuente en adultos, solo el 1-4 % ocurre en menores de 25-30 años. Su presentación suele confundirse con otras patologías, lo cual lleva a significativas demoras diagnósticas. Dada su baja incidencia, pocos pediatras se enfrentarán con algún caso a lo largo de su carrera. Sin embargo, existen en la niñez múltiples síndromes hereditarios que predisponen al CCR. El objetivo de esta revisión es brindar una actualización sobre los síndromes predisponentes al CCR. Se revisarán las indicaciones de tamizaje, dado que el diagnóstico precoz en estadios localizados es el principal factor pronóstico. Además, se fortalecerán las herramientas de consejería genética para el paciente y su familia. A su vez, se discutirán las manifestaciones clínicas e histológicas y los factores pronósticos propios del CCR en la población pediátrica. Si bien las guías de tratamiento se extrapolan de la experiencia en adultos, se resumirán los lineamientos terapéuticos.


Although colorectal carcinoma (CRC) is the third most common type of cancer in adults, only 1-4 % of cases are reported in individuals younger than 25-30 years. Its presentation is usually confused with other diseases, leading to significant delays in diagnosis. Given its low incidence, few pediatricians will see a case throughout their practice. However, multiple hereditary syndromes during childhood predispose to CRC.The objective of this review is to provide an update on syndromes predisposing to CRC. Screening indications will be reviewed because an early diagnosis during localized stages is the main prognostic factor. In addition, patient and family genetic counseling tools will be enhanced. In turn, the clinical and histological manifestations and prognostic factors typical of CRC in the pediatric population will be discussed. Although treatment guidelines are extrapolated from the adult experience, therapy guidelines will be summarized here.


Subject(s)
Humans , Child , Adolescent , Colorectal Neoplasms/diagnosis , Colorectal Neoplasms/genetics , Colorectal Neoplasms/epidemiology , Mass Screening , Incidence
2.
Arq. gastroenterol ; 58(1): 55-60, Jan.-Mar. 2021. tab, graf
Article in English | LILACS | ID: biblio-1248983

ABSTRACT

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.


Subject(s)
Humans , Male , Female , Colorectal Neoplasms/genetics , DNA Methylation , Prognosis , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Promoter Regions, Genetic , CpG Islands , Intercellular Signaling Peptides and Proteins/genetics
3.
Article in English | WPRIM | ID: wpr-880633

ABSTRACT

OBJECTIVES@#To explore the correlation between cytosine-phosphoric-guanylic (CpG) site of Septin 9 gene and colorectal cancer, and to develop a real-time PCR detection system in plasma in patients with colorectal cancer.@*METHODS@#The methylation of training samples was detected by high-throughput sequencing technology, and the sites highly consistent with the clinical information of colorectal cancer were identified. Then the detection system of real-time PCR was designed to analyze the consistency of plasma and tissue based on methylationa sensitive enzyme digestion. Finally, 100 clinical trials were conducted to evaluate the performance of the detection system with the methylation sensitive enzyme digestion-real-time PCR.@*RESULTS@#The highly consistent sites, which were selected by high-throughput sequencing from 71 training set samples, was the 38th CpG. Based on the detection region, the screened methylation sensitive enzymes were @*CONCLUSIONS@#The 38th CpG site of Septin 9 detected by the detection system of methylation sensitive enzyme digestion-real-time PCR can highly predict the occurrence of colorectal cancer with great clinical application value.


Subject(s)
Colorectal Neoplasms/genetics , CpG Islands/genetics , DNA , DNA Methylation , Humans , Plasma/metabolism , Septins/metabolism
4.
Article in English | WPRIM | ID: wpr-880631

ABSTRACT

OBJECTIVES@#Radiotherapy is one of the main therapies for colorectal cancer, but radioresistance often leads to radiotherapy failure. To improve the radioresistance, we explore the effect of oligomycin A, the H@*METHODS@#The effects of different concentrations of oligomycin A on the survival rate and glycolysis of HT29 colorectal cancer cells at different time points were investigated via MTT and glycolysis assay. siRNA-PFK1 was synthesized in vitro and transfected into HT29 cells. The effects of oligomycin A on radiosensitivity of HT29 colorectal cancer cells were measured via MTT and colony formation assay. Western blotting was used to detect the effect of oligomycin A on the expression of glycolytic enzyme PFK1. We compared difference between the effects of siRNA-PFK1 group and oligomycin A combined with siRNA-PFK1 group on cell survival and glycolysis. After 4 Gy X-ray irradiation, the effects of cell survival and glycolysis between the siRNA-PFK1 group and the oligomycin A combined with siRNA-PFK1 group were compared.@*RESULTS@#Compared with the 0 μmol/L oligomycin A group, the cell survival rate of HT29 cells treated with 4 μmol/L oligomycin A was significantly increased (@*CONCLUSIONS@#Oligomycin A can promote the radioresistance of HT29 colorectal cancer cells, which may be related to up-regulation of the PFK1 expression and increase of cell glycolysis.


Subject(s)
Cell Line, Tumor , Colorectal Neoplasms/genetics , HT29 Cells , Humans , Oligomycins/pharmacology , Radiation Tolerance
5.
Article in English | WPRIM | ID: wpr-922585

ABSTRACT

OBJECTIVES@#The biomarkers targeting colorectal cancer (CRC) prognosis are short of high accuracy and sensitivity in clinic. Through bioinformatics analysis, we aim to identify and confirm a series of key genes referred to the diagnosis and prognosis of CRC.@*METHODS@#GSE31905, GSE35279, and GSE41657 were selected as complete RNA sequencing data sets of CRC and colorectal mucosa (CRM) tissues from the NCBI-GEO database, and the differentially expressed genes (DEGs) were analyzed. The common DEGs in these 3 data sets were obtained by Venn map, and enriched by STRING network system and Cytoscape software. The Kaplan-Meier plotter website was used to verify the correlation between the enriched genes and the prognosis of CRC.@*RESULTS@#For the whole RNA sequencing data sets of CRC and normal intestinal mucosa samples, the DEGs of CRC and CRM in the 3 data sets (|log@*CONCLUSIONS@#The above 11 genes verified by bioinformatics retrieval and analysis can predict the poor prognosis of CRC to a certain extent, and they provide a possible target for the diagnosis and treatment of CRC.


Subject(s)
Biomarkers, Tumor/metabolism , Colorectal Neoplasms/genetics , Computational Biology , Formins , Gene Expression Profiling , Gene Expression Regulation, Neoplastic , Glycoproteins , Humans , Intercellular Signaling Peptides and Proteins , Oncogenes , Prognosis , Protein Interaction Maps
6.
Article in Chinese | WPRIM | ID: wpr-921569

ABSTRACT

Right-sided colon cancer and left-sided colorectal cancer have significant differences in epidemiology,clinical features,tumor differentiation,response to treatment,prognosis,and molecular characteristics.The former has lower prevalence than the latter and is mainly associated with female and elderly patients,with poor tumor differentiation,strong invasion,poor prognosis,and weak response to epidermal growth factor receptor inhibitors.Thus,it is generally believed that the primary location of colorectal cancer is closely associated with prognosis,acting as an independent prognostic factor for therapeutic efficacy.Recent studies have revealed the genetic differences between right-sided colon cancer and left-sided colorectal cancer,providing explanations for the biological differences.This review summarizes the recent advances on the differences between left-and right-sided colorectal cancer.


Subject(s)
Aged , Colorectal Neoplasms/genetics , Female , Humans , Prognosis
7.
Chinese Medical Journal ; (24): 2340-2352, 2021.
Article in English | WPRIM | ID: wpr-921125

ABSTRACT

BACKGROUND@#Emerging evidence indicates that the sineoculis homeobox homolog 1-eyes absent homolog 1 (SIX1-EYA1) transcriptional complex significantly contributes to the pathogenesis of multiple cancers by mediating the expression of genes involved in different biological processes, such as cell-cycle progression and metastasis. However, the roles of the SIX1-EYA1 transcriptional complex and its targets in colorectal cancer (CRC) are still being investigated. This study aimed to investigate the roles of SIX1-EYA1 in the pathogenesis of CRC, to screen inhibitors disrupting the SIX1-EYA1 interaction and to evaluate the efficiency of small molecules in the inhibition of CRC cell growth.@*METHODS@#Real-time quantitative polymerase chain reaction and western blotting were performed to examine gene and protein levels in CRC cells and clinical tissues (collected from CRC patients who underwent surgery in the Department of Integrated Traditional and Western Medicine, West China Hospital of Sichuan University, between 2016 and 2018, n = 24). In vivo immunoprecipitation and in vitro pulldown assays were carried out to determine SIX1-EYA1 interaction. Cell proliferation, cell survival, and cell invasion were determined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, clonogenic assay, and Boyden chamber assay, respectively. The Amplified Luminescent Proximity Homogeneous Assay Screen (AlphaScreen) method was used to obtain small molecules that specifically disrupted SIX1-EYA1 interaction. CRC cells harboring different levels of SIX1/EYA1 were injected into nude mice to establish tumor xenografts, and small molecules were also injected into mice to evaluate their efficiency to inhibit tumor growth.@*RESULTS@#Both SIX1 and EYA1 were overexpressed in CRC cancerous tissues (for SIX1, 7.47 ± 3.54 vs.1.88 ± 0.35, t = 4.92, P = 0.008; for EYA1, 7.61 ± 2.03 vs. 2.22 ± 0.45, t = 6.73, P = 0.005). The SIX1/EYA1 complex could mediate the expression of two important genes including cyclin A1 (CCNA1) and transforming growth factor beta 1 (TGFB1) by binding to the myocyte enhancer factor 3 consensus. Knockdown of both SIX1 and EYA1 could decrease cell proliferation, cell invasion, tumor growth, and in vivo tumor growth (all P < 0.01). Two small molecules, NSC0191 and NSC0933, were obtained using AlphaScreen and they could significantly inhibit the SIX1-EYA1 interaction with a half-maximal inhibitory concentration (IC50) of 12.60 ± 1.15 μmol/L and 83.43 ± 7.24 μmol/L, respectively. Administration of these two compounds could significantly repress the expression of CCNA1 and TGFB1 and inhibit the growth of CRC cells in vitro and in vivo.@*CONCLUSIONS@#Overexpression of the SIX1/EYA1 complex transactivated the expression of CCNA1 and TGFB1, causing the pathogenesis of CRC. Pharmacological inhibition of the SIX1-EYA1 interaction with NSC0191 and NSC0933 significantly inhibited CRC cell growth by affecting cell-cycle progression and metastasis.


Subject(s)
Animals , Cell Line, Tumor , Cell Proliferation , Colorectal Neoplasms/genetics , Gene Expression Regulation, Neoplastic , Genes, Homeobox , Homeodomain Proteins/metabolism , Humans , Intracellular Signaling Peptides and Proteins , Mice , Mice, Nude , Nuclear Proteins/genetics , Protein Tyrosine Phosphatases/genetics
8.
Braz. j. med. biol. res ; 54(8): e10940, 2021. graf
Article in English | LILACS | ID: biblio-1285675

ABSTRACT

Recently, an increasing number of studies have reported that dysregulation of circular RNA (circRNA) expression plays critical roles in the progression of several cancers, including colorectal cancer (CRC). However, the detailed molecular mechanisms of circRNAs involvement in CRC remain largely unknown. Here, we confirmed that the level of circEGFR was significantly increased in CRC tissues compared to matched adjacent non-tumor tissues, and a high level of circEGFR was correlated with poor clinicopathological characteristics and poor prognosis in patients with CRC. Moreover, increased circEGFR expression promoted CRC cell proliferation, migration, and invasion in vitro. Mechanistically, circEGFR acted as a ceRNA for miR-106a-5p to relieve the repressive effect of miR-106a-5p on DDX5 mRNA. Moreover, circEGFR enhanced DDX5 expression, thereby upregulating p-AKT levels. Together, these findings showed that circEGFR promoted CRC cell proliferation, migration, and invasion through the miR-106a-5p/DDX5/AKT axis, and may serve as a promising diagnostic marker and therapeutic target for CRC patients.


Subject(s)
Humans , Colorectal Neoplasms/genetics , MicroRNAs/genetics , Gene Expression Regulation, Neoplastic , Cell Movement/genetics , Cell Line, Tumor , Cell Proliferation/genetics , DEAD-box RNA Helicases , RNA, Circular
9.
ABCD arq. bras. cir. dig ; 34(4): e1637, 2021. tab, graf
Article in English, Portuguese | LILACS | ID: biblio-1360017

ABSTRACT

RESUMO - INTRODUÇÃO: O papilomavírus humano (HPV) é agente das doenças sexualmente transmissíveis de maior prevalência no mundo que estão associadas ao câncer do colo do útero e canal anal. A ação do HPV na carcinogênese colorretal não está ainda estabelecida. OBJETIVO: Estudar a eventual correlação entre a presença do HPV tipo 16 e a expressão gênica da proteína p16INK4a e da oncoproteína E7 de HPV e de seus níveis no tecido do carcinoma colorretal. METODOS: Estudo retrospectivo caso-controle de 79 doentes com carcinoma colorretal divididos em dois grupos: HPV presente e HPV ausente. Foi realizada reação em cadeia da polimerase (PCR), além da hibridização do tipo dot blot para o HPV 16 e o HPV 18 Amostras do tecido colorretal também foram submetidas ao estudo imuno-histoquimico para avaliar o nível tecidual das proteínas E7 e p16INK4a. RESULTADOS: O HPV foi identificado em 36 (45,6%) casos. Não houve diferença significante entre os grupos quanto ao sexo (p=0,056), idade (p=0,1), localização cólica e/ou retal (0,098) e presença do HPV. A expressão gênica da oncoproteína E7 de HPV estava presente em 3,12% dos casos (p=0,9) e a expressão da proteína p16INK4a foi observada em 46,3% (p=0,27) dos indivíduos com detecção do HPV. CONCLUSÃO: A expressão gênica e os níveis teciduais da oncoproteína E7 e da proteína p16INK4a encontrados nos pacientes positivos para o HPV sugerem a ausência de atividade oncogênica do HPV tipo 16 no carcinoma colorretal.


ABSTRACT - BACKGROUND: Human papillomavirus (HPV) is the agent of the most prevalent sexually transmitted diseases in the world associated with cervix and anal canal cancer. The action of HPV on colorectal carcinogenesis is not yet established. OBJECTIVE: This research aimed to study the possible correlation between the presence of HPV16 and the gene expression of p16INK4a protein and HPV E7 oncoprotein and their levels in colorectal carcinoma tissue. METHODS: A retrospective case-control study of 79 patients with colorectal carcinoma was divided into two groups: HPV-positive and HPV-negative. The polymerase chain reaction was performed, in addition to dot-blot hybridization for HPV16 and HPV18. Colorectal tissue samples were also subjected to immunohistochemical study to assess the tissue level of E7 and p16INK4a proteins. RESULTS: HPV was identified in 36 (45.6%) cases. There was no significant difference between groups regarding gender (p=0.056), age (p=0.1), colic and/or rectal location (0.098), and presence of HPV. Gene expression of HPV E7 oncoprotein was present in 3.12% of cases (p=0.9), and p16INK4a protein expression was observed in 46.3% (p=0.27) of those selected with HPV detection. CONCLUSION: Gene expression and tissue levels of E7 oncoprotein and p16INK4a protein found in HPV-positive patients suggest the absence of HPV16 oncogenic activity in colorectal carcinoma.


Subject(s)
Humans , Female , Colorectal Neoplasms/genetics , Colorectal Neoplasms/virology , Cyclin-Dependent Kinase Inhibitor p16/genetics , Papillomavirus Infections/genetics , Papillomavirus E7 Proteins/genetics , DNA, Viral , Case-Control Studies , Retrospective Studies , Human papillomavirus 16/genetics
10.
ABCD arq. bras. cir. dig ; 34(1): e1574, 2021. tab, graf
Article in English, Portuguese | LILACS | ID: biblio-1284903

ABSTRACT

ABSTRACT Background: Inhibitors of the epidermal growth factor (EGFR) represent an effective therapeutic option for patients with metastatic colorectal carcinoma, free of activating mutations in KRAS and NRAS. However, the research of mutations is of high cost and scarcely accessible. The expression of the EGFR by immunohistochemistry predicting the mutation status of the expanded RAS (KRAS and NRAS), may allow treatment by a diagnostic method less costly and more accessible. Aim: Investigate the correlation between the clinical-pathological data, the cytoplasmic-membrane expression of the EGFR and the mutational status of the expanded RAS. Method: A total of 139 patients with colorectal carcinoma from the archives of Instituto Goiano de Oncologia e Hematologia were evaluated. Results: Mutation of the expanded RAS was detected in 78 (56.1%) cases. The EGFR expression was stratified in 23 (16.5%) "positive", 49 (35.2%) "negative" and 67 (48.2%) "uncertain". No significant correlation was found between the mutational status of the RAS and the EGFR expression in comparison to age, gender, location, histological type, histological grade and stage. From 23 "positive" cases, 21 (91.3%) showed wild-type RAS gene, and 49 "negative", 41 (83.7%) presented mutation, resulting in a strong association between EGFR "positive", "negative" groups and the mutational status of the RAS (p<0.001), with 86.1% of accuracy. Conclusions: The cytoplasmic-membrane analysis of the EGFR expression stratified into "positive", "negative" and "uncertain" predicts mutational status of the RAS in 51.7% of the cases (p<0.001), with 86.1% of accuracy.


RESUMO Racional: Inibidores do fator de crescimento epidermal (EGFR) representam opção de terapia efetiva para o câncer colorrectal metastático, na ausência de ativação de mutações KRAS e NRAS. Entretanto, a pesquisa de mutações é cara e pouco acessível. A expressão de EGFR por imuno-histoquímica predizendo o status mutacional do RAS expandido (KRAS e NRAS) poderia permitir o tratamento por método diagnóstico menos caro e mais acessível. Objetivo: Investigar a correlação entre os dados clinicopatológicos, a expressão de EGFR na membrana citoplasmática e o status mutacional do RAS expandido. Método: Estudo retrospectivo de acurácia envolvendo 139 pacientes com carcinoma colorretal. Resultado: A mutação do RAS expandido foi detectada em 78 (56,1%) casos. A expressão de EGFR foi estratificada em 23 (16,5%) casos "positivos", 49 (35,2%) casos "negativos" e 67 (48,2%) "duvidosos". Não houve correlação significante entre o status mutacional do RAS e a expressão de EGFR em relação a idade, gênero, local do tumor, tipo histológico, grau histológico e estádio clínico. Em 23 casos "positivos", 21 (91,3%) mostraram gene RAS tipo selvagem, e em 49 "negativos", 41 (83,7%) apresentaram mutação, resultando em forte associação entre grupos EGFR "positivo" ou "negativo" e o status mutacional do RAS (p<0.001), com 86,1% de acurácia. Conclusão: A análise da expressão de EGFR na membrana citoplasmática estratificada em "positivo", "negativo" e "duvidoso" prediz o status mutacional do RAS em 51,7% dos casos (p<0.001), com 86,1% de acurácia.


Subject(s)
Humans , Colorectal Neoplasms/genetics , Proto-Oncogene Proteins B-raf/genetics , Epidermal Growth Factor , ErbB Receptors/genetics , Mutation
11.
Rev. Assoc. Med. Bras. (1992) ; 66(11): 1530-1535, Nov. 2020. tab, graf
Article in English | SES-SP, LILACS, SES-SP | ID: biblio-1143641

ABSTRACT

SUMMARY OBJECTIVE: Long noncoding RNAs (lncRNAs) have been proven to exhibit distinct functions on the convoluted processes of tumor developments. Some studies on the biological functions of lncRNA MAFG-AS1 (MAFG-AS1) in cancers revealed that they may serve as an oncogene in some kinds of tumors, including colorectal cancer (CRC). However, little is known about the role of MAFG-AS1 in the prognostic of CRC. METHODS: A public dataset was mined for the screening of dysregulated lncRNAs in CRC. Quantitative real-time reverse transcription-polymerase chain reaction(qPCR) was used to compare the levels of MAFG-AS1 between paired MAFG-AS1 specimens and normal adjacent tissues. The correlations between MAFG-AS1 and clinic pathological features in CRC were analyzed using the chi-square test. The log-rank test and Kaplan-Meier test were carried out to compare the survival time of patients with high and low expressions of MAFG-AS1. Cox regression was applied for univariate and multivariate assays to validate whether MAFG-AS1 could be an independent factor in the prognosis of CRC. RESULTS: We found that the distinct upregulation of MAFG-AS1 in various tumors was a common event. MAFG-AS1 was distinctly up-regulated in CRC specimens compared to matched non-tumor specimens (p < 0.01). High MAFG-AS1 expressions were closely associated with depth of invasion (p = 0.011) and TNM stage (p = 0.022). Survival assays revealed that patients with high expression of MAFG-AS1 have a shorter overall survival (p = 0.0030) and disease-free survival (p = 0.0002). CONCLUSIONS: MAFG-AS1 can serve as a novel potential biomarker to predict CRC patients' survival time.


RESUMO OBJETIVO: RNAs longos não codificantes (lncRNAs) comprovadamente apresentam funções distintas no complicado processo de desenvolvimento de tumores. Alguns estudos sobre as funções biológicas dos lncRNA (MAFG-AS1) em cânceres revelaram que eles podem funcionar como um oncogene em alguns tipos de tumores, inclusive no câncer colorretal (CCR). No entanto, pouco é conhecido sobre o papel do MAFG-AS1 no prognóstico do CCR. MÉTODOS: Um conjunto de dados públicos foi analisado em busca de lncRNAs desregulados em casos de CCR. Uma análise quantitativa de reação em cadeia de polimerase precedida de transcrição reversa (qPCR) em tempo real foi utilizada para comparar os níveis de MAFG-AS1 entre pares de amostras de MAFG-AS1 normal e tecidos adjacentes. As correlações entre MAFG-AS1 e características clínico-patológicas do CCR foram analisadas através do teste qui-quadrado. Os testes de Log-rank e Kaplan-Meier foram utilizados para comparar o tempo de sobrevida de pacientes com expressões altas e baixas do MAFG-AS1. A regressão de Cox foi aplicada para ensaios uni e multivariados para validar se MAFG-AS1 poderia ser um fator independente no prognóstico do CCR. RESULTADOS: Observamos que a regulação aumentada de MAFG-AS1 em vários tumores foi um evento comum. MAFG1 estava claramente com a regulação aumentada em espécimes de CCR quando comparado ao de espécimes equivalentes não-tumorais (p < 0,01). Altas expressões de MAFG-AS1 estavam associadas à profundidade de invasão (p = 0,011) e classificação no sistema TNM (p = 0,022). As análises de sobrevida revelaram que pacientes com expressões elevadas do MAFG-AS1 tiveram uma diminuição significativa da sobrevida global (p = 0,0030) e da sobrevida livre de doença (p = 0,0002). CONCLUSÃO: MAFG-AS1 pode ser um novo potencial biomarcador para predizer o tempo de sobrevida de pacientes de CCR.


Subject(s)
Humans , Colorectal Neoplasms/genetics , Prognosis , Gene Expression Regulation, Neoplastic , Up-Regulation , Cell Proliferation , Kaplan-Meier Estimate , RNA, Long Noncoding/genetics
12.
Rev. argent. coloproctología ; 31(2): 51-53, jun. 2020.
Article in English, Spanish | LILACS | ID: biblio-1117007

ABSTRACT

Los contenidos de este capítulo se basan en la 3a edición de las Clínicas Quirúrgicas de Cáncer Colorrectal. C. Vaccaro y N. Peralta. del hospital ediciones 2020 (en prensa)


Subject(s)
Colorectal Neoplasms/genetics , Biomarkers, Tumor/genetics , Precision Medicine/trends , Pharmacogenetics/trends , Colorectal Neoplasms/etiology , Colorectal Neoplasms/therapy , Molecular Epidemiology/trends , Mutation , Neoplasm Metastasis/genetics , Neoplasm Metastasis/therapy
13.
Rev. méd. Chile ; 148(6): 858-867, jun. 2020. graf
Article in Spanish | LILACS | ID: biblio-1139382

ABSTRACT

Colorectal (CRC) is one of the most common types of cancer worldwide. Most tumors develop from an adenoma in a period of 10 to 15 years, but some may appear without previous adenomatous lesions. Seventy-five percent of colorectal cancers are sporadic, 20% have a family component (first or second-degree relatives with CRC) and 5% have a hereditary predisposition with a Mendelian pattern. The epidemiological evolution in the recent years in Chile has a worrisome evolution and the treatment costs of advanced stages are a burden for the healthcare system. We herein highlight the main Chilean medical and scientific contributions on the pathogenesis, early diagnosis, and treatment of CRC, which lead to its better understanding, and therefore better management, based on local evidence.


Subject(s)
Humans , Colorectal Neoplasms/diagnosis , Colorectal Neoplasms/genetics , Colorectal Neoplasms/epidemiology , Adenoma , Chile/epidemiology , Genetic Predisposition to Disease
14.
Rev. Hosp. Ital. B. Aires (2004) ; 40(1): 17-24, mar. 2020. ilus
Article in Spanish | LILACS | ID: biblio-1100762

ABSTRACT

Se estima que aproximadamente 100 trillones de microorganismos (incluidos bacterias, virus y hongos) residen en el intestino humano adulto y que el total del material genético del microbioma es 100 veces superior al del genoma humano. Esta comunidad, conocida como microbioma se adquiere al momento del nacimiento a través de la flora comensal de la piel, vagina y heces de la madre y se mantiene relativamente estable a partir de los dos años desempeñando un papel crítico tanto en el estado de salud como en la enfermedad. El desarrollo de nuevas tecnologías, como los secuenciadores de próxima generación (NGS), permiten actualmente realizar un estudio mucho más preciso de ella que en décadas pasadas cuando se limitaba a su cultivo. Si bien esto ha llevado a un crecimiento exponencial en las publicaciones, los datos sobre las poblaciones Latinoamérica son casi inexistentes. La investigación traslacional en microbioma (InTraMic) es una de las líneas que se desarrollan en el Instituto de Medicina Traslacional e Ingeniería Biomédica (IMTIB). Esta se inició en 2018 con la línea de cáncer colorrectal (CCR) en una colaboración con el Colorectal Cancer Research Group del Leeds Institute of Medical Research en el proyecto Large bowel microbiome disease network: Creation of a proof of principle exemplar in colorectal cancer across three continents. A fines de 2019 se cumplió el objetivo de comprobar la factibilidad de la recolección, envío y análisis de muestras de MBF en 5 continentes, incluyendo muestras provenientes de la Argentina, Chile, India y Vietnam. Luego de haber participado de capacitaciones en Inglaterra, se ha cumplido con el objetivo de la etapa piloto, logrando efectivizar la recolección, envío y análisis metagenómico a partir de la secuenciación de la región V4 del ARNr 16S. En 2019, la línea de enfermedad de hígado graso no alcohólico se sumó a la InTraMic iniciando una caracterización piloto en el marco de una colaboración con el laboratorio Novartis. Los resultados de ese estudio, así como el de cáncer colorrectal, están siendo enviados a publicación. En 2020, con la incorporación de la línea de trasplante alogénico de células progenitoras hematopoyéticas, fue presentado un proyecto para un subsidio del CONICET que ha superado la primera etapa de evaluación. En el presente artículo se brinda una actualización sobre la caracterización taxonómica de microbioma y se describen las líneas de investigación en curso. (AU)


It is estimated that approximately 100 trillion microorganisms (including bacteria, viruses, and fungi) reside in the adult human intestine, and that the total genetic material of the microbiome is 100 times greater than that of the human genome. This community, known as the microbiome, is acquired at birth through the commensal flora of the mother's skin, vagina, and feces and remains relatively stable after two years, playing a critical role in both the state of health and in disease. The development of new technologies, such as next-generation sequencers (NGS), currently allow for a much more precise study of it than in past decades when it was limited to cultivation. Although this has led to exponential growth in publications, data on Latin American populations is almost non-existent. Translational research in microbiome (InTraMic) is one of the lines developed at the Instituto de Medicina Traslacional e Ingeniería Biomédica (IMTIB). This started in 2018 with the Colorectal Cancer Line (CRC) in a collaboration with the Colorectal Cancer Research Group of the Leeds Institute of Medical Research in the project "Large bowel microbiome disease network: Creation of a proof of principle exemplar in colorectal cancer across three continents". At the end of 2019, the objective of verifying the feasibility of collecting, sending and analyzing MBF samples on 5 continents, including samples from Argentina, Chile, India and Vietnam, was met. After having participated in training in England, the objective of the pilot stage has been met, achieving the collection, delivery and metagenomic analysis from the sequencing of the V4 region of the 16S rRNA. In 2019, the non-alcoholic fatty liver disease line joined InTraMic, initiating a pilot characterization in the framework of a collaboration with the Novartis laboratory. The results of that study, as well as that of colorectal cancer, are being published. In 2020, with the incorporation of the allogeneic hematopoietic stem cell transplantation line, a project was presented for a grant from the CONICET that has passed the first stage of evaluation. This article provides an update on the taxonomic characterization of the microbiome and describes the lines of ongoing research. (AU)


Subject(s)
Humans , Translational Medical Research/organization & administration , Gastrointestinal Microbiome/genetics , Transplantation, Homologous , Vietnam , Aztreonam/therapeutic use , RNA, Ribosomal, 16S/analysis , Colorectal Neoplasms/genetics , Colorectal Neoplasms/microbiology , Colorectal Neoplasms/epidemiology , Classification/methods , Hematopoietic Stem Cell Transplantation , Metagenomics , Translational Medical Research/methods , High-Throughput Nucleotide Sequencing/trends , Non-alcoholic Fatty Liver Disease/genetics , Non-alcoholic Fatty Liver Disease/microbiology , Non-alcoholic Fatty Liver Disease/pathology , Non-alcoholic Fatty Liver Disease/epidemiology , Gastrointestinal Microbiome/physiology , India , Latin America , Occult Blood
15.
Rev. Assoc. Med. Bras. (1992) ; 66(1): 42-47, Jan. 2020. graf
Article in English | LILACS | ID: biblio-1091906

ABSTRACT

SUMMARY OBJECTIVE ADAMTS4 is a member of the ADAMTS4 family, which secretes proteinases. The mechanism of tumor metastasis may be correlated to its promotion of angiogenesis. It was determined whether ADAMTS4 participates in colorectal cancer progression. Methods The expression in clinical samples and CRC cell lines was investigated. Using immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), and RT-PCR, the expression of ADAMTS4 was determined in colorectal tumors of different cancer stages and anatomic sites, and in three cell lines of different aggressiveness. Results The overexpression of ADAMTS4 was observed in tissue samples by IHC, and this was mainly located in the cytoplasm, as detected by FISH. The qRT-PCR and western blot analyses further supported the clinical sample findings. Conclusion The present data support the notion that the overexpression of ADAMTS4 in CRC might be useful as a non-invasive biomarker for detecting CRC in patients.


RESUMO OBJETIVO ADAMTS4 é um membro da família ADAMTS4, que secreta proteinases. O mecanismo da metástase do tumor pode ser correlacionado a sua promoção da angiogênese. Determinou-se se ADAMTS4 participa na progressão do câncer colorretal. Métodos A expressão em amostras clínicas e linhas de células CRC foi investigada. Usando a imuno-histoquímica (IHC), a hibridação fluorescente in situ (HFIS) e o RT-PCR, a expressão de ADAMTS4 foi determinada em tumores colorretais de diferentes estágios do câncer e locais anatômicos, e em três linhas de células de níveis de agressividade distintos. Resultados A superexpressão de ADAMTS4 foi observada em amostras de tecido por IHC, e esta foi localizada principalmente no citoplasma, como detectado pelo HFIS. O qRT-PCR e a análise de wester blot corroboraram os resultados clínicos da amostra. Conclusão Os dados atuais corroboram a noção de que a superexpressão de ADAMTS4 no CRC pode ser útil como um biomarcador não invasivo para a detecção de CRC em pacientes.


Subject(s)
Humans , Male , Female , Aged , Colorectal Neoplasms/pathology , ADAMTS4 Protein/analysis , Prognosis , Reference Values , RNA, Messenger/analysis , Immunohistochemistry , Colorectal Neoplasms/genetics , Biomarkers, Tumor , Gene Expression Regulation, Neoplastic , Up-Regulation , Blotting, Western , Analysis of Variance , In Situ Hybridization, Fluorescence , Disease Progression , Cell Line, Tumor , Middle Aged
16.
Article in Chinese | WPRIM | ID: wpr-880786

ABSTRACT

OBJECTIVE@#To explore the clinicopathological features and types of genic mutations in DNA mismatch repair (MMR) in colorectal cancer (CRC).@*METHODS@#Immunohistochemistry was used to determine the expression of MMR proteins in 1394 patients with CRC, and PCR-capillary electrophoresis (PCR-CE) was used to detect microsatellite instability (MSI) in 106 cases of defective MMR (dMMR), 46 cases of proficient MMR (pMMR) with heterogeneous expression and 147 randomly selected cases of pMMR. The relationship between the expressions of MMR proteins and the clinicopathological features of the patients was evaluated. The consistency between the results of immunohistochemistry and PCR-CE was assessed.@*RESULTS@#Immunohistochemical staining showed an incidence of dMMR of 7.6% in the patients. The main type of dMMR was co-deletion of MLH1 and PMS2, accounting for 55.7% of the total dMMR cases. The deletion of MMR proteins was significantly correlated with the patients' age, tumor location, tumor size, gross type, histological type, degree of differentiation, lymph node status and TNM stage (@*CONCLUSIONS@#The main type of dMMR is co-deletion of MLH1 and PMS2 in patients with colorectal cancer. dMMR colorectal cancer has typical clinicopathological features and a lower incidence in China than in Western countries. The results of immunohistochemistry and PCR-CE are highly consistent for detecting dMMR in colorectal cancer patients.


Subject(s)
China , Colorectal Neoplasms/genetics , DNA Mismatch Repair/genetics , Humans , Microsatellite Instability
18.
ABCD arq. bras. cir. dig ; 33(4): e1569, 2020. tab, graf
Article in English | LILACS | ID: biblio-1152636

ABSTRACT

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.


Subject(s)
Humans , Middle Aged , Colorectal Neoplasms/genetics , Colorectal Neoplasms/pathology , Adenocarcinoma/genetics , Adenocarcinoma/pathology , Colonic Neoplasms , ATP Binding Cassette Transporter, Subfamily B/metabolism , Prognosis , Rectum
19.
ABCD arq. bras. cir. dig ; 33(3): e1534, 2020. tab, graf
Article in English | LILACS | ID: biblio-1141907

ABSTRACT

ABSTRACT Background: Colorectal cancer (CRC) is one of the most common types of cancer in the world. Over time, intestinal epithelial cells undergo mutations that may lead to proliferative advantage and the emergence of cancer. Mutations in the beta-catenin pathway are amongst those described in the development of CRC. Aim: To verify the existence of a relation between the presence of Wnt3, beta-catenin and CDX2 in colorectal cancer samples and clinical outcomes such as disease progression or death. Method: Wnt3a, beta-catenin and CDX2 immunohistochemistry was performed on CRC tissue microarray samples (n=122), and analysis regarding the relation between biomarker expression and disease progression or death was performed. Results: No significant difference was found between the presence or absence of CDX2, beta-catenin or Wnt3a expression and clinical stage, tumor grade, disease progression or death. Conclusion: CDX2, beta-catenin and Wnt3a are not useful to predict prognosis in patients with CRC.


RESUMO Racional: O câncer colorretal (CCR) é um dos tipos mais comuns no mundo. As células epiteliais intestinais podem sofrer mutações que ocasionam vantagem proliferativa e culminam com o surgimento do câncer. Mutações da via da beta-catenina foram descritas entre as que podem ocasioná-lo. Objetivo: Verificar a existência de relação entre a expressão de Wnt3, beta-catenina e CDX2 em amostras de câncer colorretal com os eventos clínicos progressão de doença e óbito. Método: Foi realizada análise imunoistoquímica de Wnt3a, beta-catenina e CDX2 em blocos multiamostrais de CRC (n=122), e avaliada a relação entre a expressão dos biomarcadores e os desfechos progressão de doença e óbito. Resultados: Não foram encontradas diferenças significativas entre a expressão ou ausência de CDX2, beta-catenina ou Wnt3a e estádio clínico, grau de diferenciação tumoral, presença de progressão de doença ou evolução ao óbito. Conclusão: Os marcadores CDX2, beta-catenina e Wnt3a não são úteis para predizer prognóstico em pacientes com CCR.


Subject(s)
Humans , Colorectal Neoplasms/diagnosis , beta Catenin/genetics , Wnt3 Protein/genetics , CDX2 Transcription Factor/genetics , Immunohistochemistry , Colorectal Neoplasms/genetics , Disease Progression
20.
ABCD arq. bras. cir. dig ; 33(3): e1524, 2020. tab, graf
Article in English | LILACS | ID: biblio-1141902

ABSTRACT

ABSTRACT Background: KRAS mutations are important events in colorectal carcinogenesis, as well as negative predictors of response to EGFR inhibitors treatment. Aim: To investigate the association of clinical-pathological features with KRAS mutations in colorectal cancer patients treated. Methods: Data from 69 patients with colorectal cancer either metastatic at diagnosis or later, were retrospectively analyzed. The direct sequencing and pyrosequencing techniques were related to KRAS exon 2. The mutation diagnosis and its type were determined. Results: KRAS mutation was identified in 43.4% of patients. The most common was c.35G>T (p.G12V), c.35G>A (p.G12D) and c.38G>A (p.G13D). No correlation was found between KRAS mutation and age (p=0.646) or gender (p=0.815). However, mutated group had higher CEA levels at admission (p=0.048) and codon 13 mutation was associated with involvement of more than one metastatic site in disease progression (p=0.029). Although there was no association between primary tumor site and mutation diagnosis (p=0.568), primary colon was associated with worse overall survival (p=0.009). Conclusion: The KRAS mutation was identified in almost half of patients. Mutated KRAS group had higher levels of CEA at admission and the mutation at codon 13 was associated with involvement of more than one metastatic site in the course of the disease. Colon disease was associated with the worst overall survival.


RESUMO Racional: Mutações KRAS são eventos importantes na carcinogênese colorretal como preditores negativos de resposta ao tratamento. Objetivo: Investigar a associação de características clinicopatológicas com mutações no KRAS em pacientes com câncer colorretal tratados. Métodos: Sessenta e nove pacientes com câncer colorretal metastáticos ao diagnóstico ou posteriormente foram analisados. As técnicas de sequenciamento direto e pirosequenciamento foram relacionadas ao éxon 2 do KRAS e o diagnóstico da mutação e seu tipo foram determinados. Resultados: A mutação KRAS foi identificada em 43,4% dos pacientes, c.35G>T (p.G12V), c.35G>A (p.G12D) e c.38G>A (p.G13D). Não foi encontrada correlação entre a mutação KRAS e a idade (p=0,646) ou o gênero (p=0,815). No entanto, o grupo mutado apresentou níveis mais altos de CEA na admissão (p=0,048). A mutação do códon 13 foi associada ao envolvimento de mais de um local metastático na progressão da doença (p=0,029); não houve associação entre o local primário do tumor e o diagnóstico de mutação (p=0,568); a doença primária do cólon foi associada com pior sobrevida global (p=0,009). Conclusão: A mutação KRAS foi identificada em quase metade dos pacientes. O grupo KRAS mutado apresentou níveis mais altos de CEA na admissão e a mutação no códon 13 foi associada ao envolvimento de mais de um local metastático no curso da doença. A doença do cólon foi associada com pior sobrevida global.


Subject(s)
Humans , Male , Female , Adult , Middle Aged , Aged , Aged, 80 and over , Colorectal Neoplasms/genetics , Proto-Oncogene Proteins p21(ras)/genetics , Proto-Oncogene Proteins/metabolism , Colorectal Neoplasms/pathology , Retrospective Studies , Proto-Oncogene Proteins/genetics , ras Proteins/genetics , Mutation
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