The Expression Profiles of lncRNAs Are Associated with Neoadjuvant Chemotherapy Resistance in Locally Advanced, Luminal B-Type Breast Cancer.

lncRNAs are noncoding transcripts with tissue and cancer specificity. Particularly, in breast cancer, lncRNAs exhibit subtype-specific expression; they are particularly upregulated in luminal tumors. However, no gene signature-based laboratory tests have been developed for luminal breast cancer identification or the differential diagnosis of luminal tumors, since no luminal A- or B-specific genes have been identified. Particularly, luminal B patients are of clinical interest, since they have the most variable response to neoadjuvant treatment; thus, it is necessary to develop diagnostic and predictive biomarkers for these patients to optimize treatment decision-making and improve treatment quality. In this study, we analyzed the lncRNA expression profiles of breast cancer cell lines and patient tumor samples from RNA-Seq data to identify an lncRNA signature specific for luminal phenotypes. We identified an lncRNA signature consisting of LINC01016, GATA3-AS1, MAPT-IT1, and DSCAM-AS1 that exhibits luminal subtype-specific expression; among these lncRNAs, GATA3-AS1 is associated with the presence of residual disease (Wilcoxon test, p < 0.05), which is related to neoadjuvant chemotherapy resistance in luminal B breast cancer patients. Furthermore, analysis of GATA3-AS1 expression using RNA in situ hybridization (RNA ISH) demonstrated that this lncRNA is detectable in histological slides. Similar to estrogen receptors and Ki67, both commonly detected biomarkers, GATA3-AS1 proves to be a suitable predictive biomarker for clinical application in breast cancer laboratory tests.

Radio-miRs: a comprehensive view of radioresistance-related microRNAs.

Radiotherapy is a key treatment option for a wide variety of human tumors, employed either alone or alongside with other therapeutic interventions. Radiotherapy uses high-energy particles to destroy tumor cells, blocking their ability to divide and proliferate. The effectiveness of radiotherapy is due to genetic and epigenetic factors that determine how tumor cells respond to ionizing radiation. These factors contribute to the establishment of resistance to radiotherapy, which increases the risk of poor clinical prognosis of patients. Although the mechanisms by which tumor cells induce radioresistance are unclear, evidence points out several contributing factors including the overexpression of DNA repair systems, increased levels of reactive oxygen species, alterations in the tumor microenvironment, and enrichment of cancer stem cell populations. In this context, dysregulation of microRNAs or miRNAs, critical regulators of gene expression, may influence how tumors respond to radiation. There is increasing evidence that miRNAs may act as sensitizers or enhancers of radioresistance, regulating key processes such as the DNA damage response and the cell death signaling pathway. Furthermore, expression and activity of miRNAs have shown informative value in overcoming radiotherapy and long-term radiotoxicity, revealing their potential as biomarkers. In this review, we will discuss the molecular mechanisms associated with the response to radiotherapy and highlight the central role of miRNAs in regulating the molecular mechanisms responsible for cellular radioresistance. We will also review radio-miRs, radiotherapy-related miRNAs, either as sensitizers or enhancers of radioresistance that hold promise as biomarkers or pharmacological targets to sensitize radioresistant cells.

Evidencia psicométrica del Cuestionario sobre la Salud del Paciente (PHQ-9) y Escala de Ansiedad Generalizada (GAD-7) en pacientes con asesoramiento genético en Oncología / Psychometric evidence of the Patient Health Questionnaire (PHQ-9) and Generalized Anxiety Scale (GAD-7) in patients with genetic counseling in Oncology

Introducción: Los síntomas de depresión y ansiedad en pacientes que reciben Asesoramiento Genético en Oncología (AGO), se encuentran dentro de las afectaciones psicológicas más prevalentes, por lo que su identificación de forma oportuna, valida y confiable es prioritaria. Objetivo: Determinar las propiedades psicométricas del Cuestionario sobre la Salud del Paciente, PHQ-9, y de la Escala de Ansiedad Generalizada, GAD-7, en pacientes con cáncer portadores de variantes patogénicas germinales en genes de alta susceptibilidad. Método: Se empleó un diseño instrumental, transversal con un muestreo no probabilístico. Se incluyeron 163 participantes con variantes patogénicas en BRCA1/BRCA2, asociadas a cáncer hereditario, entre 19 y 79 años, (48,2 ± 11,2 años). Resultados: La validez de constructo de cada instrumento se probó a través de un análisis factorial exploratorio y confirmatorio. La GAD-7 obtuvo un α = 0,899 y 62,3 % de la varianza explicada, por otro lado, el PHQ- 9 obtuvo un α = 0,896 y 54,8 % de la varianza explicada. El análisis factorial confirmatorio sugiere que los modelos teóricos de ambos instrumentos se ajustan a un solo factor, con una consistencia e índices de validez adecuados. Discusión y conclusión: El PHQ-9 y la GAD-7 son instrumentos parsimoniosos, breves, válidos y confiables para la detección de síntomas de depresión y ansiedad en pacientes que reciben AGO, en población mexicana. Se recomienda su uso en la atención clínica (al inicio, y durante el seguimiento), así como en investigaciones futuras (AU)

Introduction: The symptoms of depression and anxiety in patients receiving Genetic Counseling in Oncology (AGO) are among the most prevalent psychological affectations, so their timely, valid, and reliable identification is a priority. Objective: To determine the psychometric properties of the Patient Health Questionnaire, PHQ-9, and the Generalized Anxiety Scale, GAD-7, in cancer patients carrying germinal pathogenic variants in high susceptibility genes. Method: An instrumental, cross-sectional design was used with a non-probabilistic sampling. 163 participants with pathogenic variants in BRCA1/BRCA2, associated with hereditary cancer, between 19 and 79 years (48.2 ± 11.2 years) were included. Statistical analysis: The construct validity of each instrument was tested through an exploratory and confirmatory factor analysis. Results: The GAD-7 obtained α = 0.899 and 62.3% of the explained variance, on the other hand, the PHQ-9 obtained α = 0.896 and 54.8% of the explained variance. Confirmatory factor analysis suggests that the theoretical models of both instruments fit a single factor, with adequate consistency and validity indices. Discussion and conclusion: The PHQ-9 and the GAD-7 are parsimonious, brief, valid and reliable instruments for the detection of symptoms of depression and anxiety in patients receiving AGO, in the Mexican population. Its use is recommended in clinical care (at baseline, and during follow-up), as well as in future research (AU)