Analysis of gene expression EGFR and KRAS, microRNA-21 and microRNA-203 in patients with colon and rectal cancer and correlation with clinical outcome and prognostic factors

Carvalho, Thais Inácio de; Novais, Paulo Cézar; Neto, Fermino Sanches Lizarte; Sicchieri, Renata Danielle; Rosa, M.S.T.; Carvalho, Camila Albuquerque Mello de; Tirapelli, Daniela Pretti da Cunha; Peria, Fernanda Maris; Rocha, José Joaquim Ribeiro da; Féres, Omar

doi:10.1590/s0102-865020170030000009

Cited by 7 publications

(8 citation statements)

References 19 publications

(18 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Em outro estudo, 15 não houve diferença da expressão de EGFR e gene KRAS entre o grupo controle e o grupo com câncer colorretal, e a expressão do gene KRAS foi maior em pacientes diagnosticados com CCR abaixo dos 60 anos de idade. Em uma comparação entre pacientes com KRAS selvagem e KRAS G13D, os pacientes com KRAS G13D tiverem uma pior resposta tumoral.…”

Section: Resultsunclassified

“…12 Apesar de um estudo correlacionar a expressão do KRAS com o grau de diferenciação do tumor 9 outro estudo determinou que a expressão do KRAS não mostrou correlação com o desfecho clínico. 15 Para Boutin et.al, 9 apesar da sinalização do KRAS oncogênico ser dispensável para o crescimento adenomatoso, ela é essencial para a progressão da invasão e metástase do CCR. De acordo com o grupo, células com KRAS mutante ativado superam as células com KRAS selvagem e sua sinalização determina um papel crítico no rompimento inicial da submucosa.…”

Section: Resultsunclassified

See 1 more Smart Citation

Expressão Das Proteínas Mutantes Do Kras No Adenocarcinoma Colorretal – Revisão Bibliografica

Guedes¹,

Bueno²,

Oliveira³

et al. 2019

Rev Pat Tocantins

View full text Add to dashboard Cite

Introdução: Os tumores colorretais foram o terceiro tipo de câncer mais diagnosticado em 2018. Na tentativa de aumentar a sobrevida de pacientes com metástases, o teste KRAS é relevante para a escolha da terapia mais apropriada para o carcinoma colorretal (CCR). O gene KRAS (Kirsten Ras Oncogene) acompanhado dos genes BRAF e NRAS é responsável por codificar as proteínas RAS da importante via de sinalização celular RAS/RAF/MEK/ERK. A presença de KRAS mutante no CCR é o principal biomarcador tecidual que indica a resistência do tumor à terapia de primeira linha com anticorpos monoclonais inibidores do EGFR (Cetuximabe e Panitumumabe). Metodologia: Foi realizado um levantamento bibliográfico na base eletrônica Google Scholar utilizando os descritores: “colorectal cancer” and “KRAS gene”. Resultados: A conversão do aminoácido glicina (G) para ácido aspártico (D) no códon 12, também chamada de KRAS G12D, é a mutação mais frequente do KRAS nas neoplasias malignas gastrointestinais. Cerca de 40% dos CCRs têm a mutação no gene KRAS nos códons 12 e 13 do éxon 2. Houve predomínio (57,4%) das mutações no sexo masculino, e todas as amostras de cólon esquerdo, 66% das de cólon direito e 51,8% das de reto apresentaram mutações no KRAS. A sinalização de células com KRAS mutante determina um papel crítico no rompimento inicial da submucosa e, por isso é essencial para a progressão da invasão e metástase do CCR. A eficácia de anti-EGFR é limitada em pacientes que possuem mutação KRAS, entretanto 20% dos pacientes com KRAS selvagem se beneficiam diante da terapia. Atualmente não há droga ou vacina que consiga focalizar efetivamente a proteína KRAS G12D em humanos. Conclusão: Pode-se inferir que o CCR é um câncer de prognostico ainda reservado. A decisão terapêutica apropriada depende do conhecimento do status mutacional do KRAS e as mutações no éxon 2 são claramente preditivas às terapias com anticorpos monoclonais inibidores do EGFR. Palavras-chave: Carcinoma colorretal; gene KRAS; mutação. ABSTRACT Introduction: Colorectal tumors were the third most diagnosed type of cancer in 2018. Trying to improve the overall survival of patients with metastasis, the KRAS test is relevant for choosing a mora appropriate therapy for the colorectal carcinoma (CRC). The KRAS gene (Kirsten Ras Oncogene) along with BRAF and NRAS genes is responsible for encoding RAS proteins from the important RAS / RAF / MEK / ERK cell signaling pathway. The presence of mutant KRAS in the CCR is the major tissue biomarker indicating the patient's resistance to first-line therapy with the monoclonal vaccine EGFR inhibitors (Cetuximabe and Panitumumabe). Methodology: A bibliographic survey was carried out in the database of Google Scholar using the descriptors: "colorectal cancer" and "KRAS gene". Results: The conversion of the amino acid glycine (G) to aspartic acid (D) at codon 12, also called KRAS G12D, is a more frequent mutation of KRAS in gastrointestinal malignancies. About 40% of the RCCs have a mutation in the KRAS gene at codons 12 and 13 of exon 2. There was a predominance (57.4%) of the mutations in the male sex, and all samples from the left colon, 66% of the right colon and 51.8% of the mutational changes in KRAS. Marking of cells with mutant KRAS determines a non-initial critical role of the submucosa and is therefore essential for progression of CCR invasion and metastasis. Anti-EGFR is limited to patients who have KRAS mutation, in addition, 20% of wild-type KRAS patients benefit from the therapy. There is currently no drug or vaccine that can concentrate on a KRAS G12D protein in humans. Conclusion: It can be inferred that the CRC still has a reserved prognosis. The multitude of KRAS and mutations in exon 2 are clearly prescribed in therapies with EGFR inhibitory monoclonal antibodies. Keywords: Colorectal cancer; KRAS gene; mutation.

show abstract

Section: Resultsunclassified

Expressão Das Proteínas Mutantes Do Kras No Adenocarcinoma Colorretal – Revisão Bibliografica

Guedes¹,

Bueno²,

Oliveira³

et al. 2019

Rev Pat Tocantins

View full text Add to dashboard Cite

show abstract

“…This did not, however, translate in a change in survival. miR-21 is often upregulated in solid tumors influencing cell proliferation, invasion, and apoptosis (18). Considered to be an oncomiR, multiple studies report its role in CRC biology as a screening, diagnostic, and prognostic biomarker (6,(19)(20)(21)(22)(23).…”

Section: Discussionmentioning

confidence: 99%

Potential of miR-21 to Predict Incomplete Response to Chemoradiotherapy in Rectal Adenocarcinoma

et al. 2020

View full text Add to dashboard Cite

Background: Patients with locally advanced rectal adenocarcinoma (LARC) are treated with neoadjuvant chemoradiotherapy (CRT). However, biomarkers for patient selection are lacking, and the association between miRNA expression and treatment response and oncological outcomes is unclear. Objectives: To investigate miRNAs as predictors of response to neoadjuvant CRT and its association with oncological outcomes. Methods: This retrospective study analyzed miRNA expression (miR-16, miR-21, miR-135b, miR-145, and miR-335) in pre-and post-chemoradiation rectal adenocarcinoma tissue and non-neoplastic mucosa in 91 patients treated with neoadjuvant CRT (50.4 Gy) and proctectomy. Two groups were defined: a pathological complete responders group (tumor regression grade-TRG 0) and a pathological incomplete responders group (TRG 1, 2, and 3). Results: miR-21 and miR-135b were upregulated in tumor tissue of incomplete responders comparing with non-neoplastic tissue (p = 0.008 and p < 0.0001, respectively). Multivariate analysis showed significant association between miR-21 in pre-CRT tumor tissue and response, with a 3.67 odds ratio (OR) of incomplete response in patients with higher miR-21 levels (p = 0.04). Although with no significance, patients treated with 5-fluorouracil (5-FU) presented reduced odds of incomplete response compared with those treated with capecitabine (OR = 0.19; 95% confidence interval (CI) 0.03-1.12, p = 0.05). Moreover, significant differences were seen in overall survival (OS) in relation to clinical TNM stage (p = 0.0004), cT (p = 0.0001), presence of distant disease (p = 0.002), mesorectal tumor deposits (p = 0.003), and tumor regression grade (p = 0.04). Conclusion: miR-21 may predict response to CRT in rectal cancer (RC).

show abstract

“…They concluded that an increased expression of miR -21 and 203 in tumor samples in relation to non-tumor samples was found. The expression of miR-203 was progressively lower in relation to the TNM staging and was higher in the patient group in clinical remission ( Carvalho et al, 2017 ). To determine the mechanisms of the malignant transformation, Bao et al (2014) conducted miR array on the colonic epithelial cells from the 3-month Muc22/2 and +/+ mice.…”

Section: Theranostic Value Of Mir In Rectal Cancermentioning

confidence: 99%

MicroRNA: Another Pharmacological Avenue for Colorectal Cancer?

Yan

Wang

et al. 2020

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

MicroRNAs (miR) are single-stranded RNA of 21-23 nucleotides in length that repress mRNA translation and induces mRNA degradation. miR acts as an endogenous factor of gene expression and plays a crucial part in cancer biology such as cell development, proliferation, differentiation, and apoptosis. Numerous research has indicated that dysregulation of miR associates with colorectal carcinogenesis. In this review article, we firstly introduce the background of miR and colorectal cancer, and the mechanisms of miR in colorectal cancer, such as the proliferation, apoptosis, and progression. Then, we summarize the theranostic value of miR in colorectal cancer. Eventually, we discuss the potential directions and perspectives of miR. This article serves as a guide for further studies and implicate miR as a potent theranostic target for colorectal cancer.

show abstract

Analysis of gene expression EGFR and KRAS, microRNA-21 and microRNA-203 in patients with colon and rectal cancer and correlation with clinical outcome and prognostic factors

Cited by 7 publications

References 19 publications

Expressão Das Proteínas Mutantes Do Kras No Adenocarcinoma Colorretal – Revisão Bibliografica

Expressão Das Proteínas Mutantes Do Kras No Adenocarcinoma Colorretal – Revisão Bibliografica

Potential of miR-21 to Predict Incomplete Response to Chemoradiotherapy in Rectal Adenocarcinoma

MicroRNA: Another Pharmacological Avenue for Colorectal Cancer?

Contact Info

Product

Resources

About