RESUMEN
BACKGROUND: According to our previous studies, the presence of amplifications of stem genes can lead to their ectopic expression and this is associated with an increased activity of tumor stem cells in these patients. This leads to a high aggressiveness of the tumor and the development of metastatic disease. The aim was to evaluate the prognostic significance of the presence of amplifications of stem genes and their expression in patients with early breast cancer (BC). METHODS: The study included 28 patients with T1NxM0 BC. We used surgical specimens, including formalin-fixed paraffin-embedded archive materials, for 8 patients. A microarray analysis was performed on high-density DNA chips from CytoScanHDArray to assess the status of copy number aberration (CNA) of stem genes locus. Gene expression was assessed using RT-qPCR. RESULTS: CNA analysis of the studied tumors of patients without chemotherapy showed that 17/18 patients without metastases did not have two or more amplifications of chromosomal regions. Ten patients had visceral metastases. In 9/10 of these patients in the primary tumor there were two or more amplifications of the stem genes locus. Two or more amplifications of stem genes locus were found in 12 patients with stage I. Hematogenous metastases did not develop in all patients. Comparison of metastasis-free survival rates in groups of patients with 1 or without amplifications and with two or more amplifications showed statistically significant differences (P = 0.01). CONCLUSION: Our studies have shown that the presence of clones with two or more amplifications of stem gene in patients with BC T1NxM0 has a significant prognostic value and determines an unfavorable prognosis for distant metastasis.
Asunto(s)
Biomarcadores de Tumor/genética , Neoplasias de la Mama/patología , Adulto , Neoplasias de la Mama/mortalidad , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Estimación de Kaplan-Meier , Factor 4 Similar a Kruppel , Factores de Transcripción de Tipo Kruppel/genética , Persona de Mediana Edad , Metástasis de la Neoplasia , Estadificación de Neoplasias , Factor 3 de Transcripción de Unión a Octámeros/genética , Análisis de Secuencia por Matrices de Oligonucleótidos , Pronóstico , Factores de Transcripción SOXE/genéticaRESUMEN
BACKGROUND: Amplification of chromosome 8q with locus 8q24 is the most common copy number aberration, and is associated with tumour progression and chemoresistance. MATERIALS AND METHODS: The study used paired samples of biopsy and surgical material from 60 patients with breast cancer. The amplification status of 8q was determined using a CytoScan HD Array microarray; complete transcriptomic analysis was performed using a Human Clariom S Assays microarray (Affymetrix, USA). RESULTS: It was shown that in 65% of cases, amplification of 8q was preserved in the tumour after neoadjuvant chemotherapy (NAC). NAC significantly enhanced the heterogeneity of the transcriptome between tumours with and without amplification of 8q. Compared with a good response, a poor response to NAC also led to increased heterogeneity of the transcriptome of residual tumours. Eight differentially expressed genes of patients with different amplification status of 8q before and after NAC overlapped. CONCLUSION: Amplification of 8q leads to a significant shift in the level of transcription of a large number of genes after exposure to chemotherapy.
Asunto(s)
Neoplasias de la Mama/genética , Cromosomas Humanos Par 8 , Amplificación de Genes , Transcriptoma , Adulto , Anciano , Biomarcadores de Tumor , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/terapia , Terapia Combinada , Biología Computacional/métodos , Femenino , Perfilación de la Expresión Génica/métodos , Regulación Neoplásica de la Expresión Génica , Frecuencia de los Genes , Humanos , Persona de Mediana Edad , Estadificación de Neoplasias , Adulto JovenRESUMEN
This review is devoted to a rare in clinical practice, but promising phenomenon of regression distant non-irradiated metastases in combination therapy of cancer patients. R. H. Mole in 1953 suggested introducing the term "abscopal effect" to denote the effect of ionizing radiation "at a distance from the irradiated volume but within the same organism." Currently, it is a hypothesis in the treatment of metastatic cancer, when there is a regression of untreated areas simultaneously with a decrease in the tumor. After the discovery of immune checkpoint cases were increase with patients treated with check-point blockade (especially lymphocyte associated protein 4, programmed cell death 1/programmed cell death 1 ligand 1) and which have an abscopal effect. This review systematizes works covering the time period from 1969 to 2019, which give cases of the abscopal effect at different localizations. However, abscopal effect is a poorly understood phenomenon. In this review, the authors tried to collect all information about the possible mechanisms of the abscopal effect, possible role in antitumor response and frequency abscopal effect at radio/immunotherapy or combined both.