ABSTRACT
Breast cancer ranks first in terms of mortality and incidence rates worldwide among women. The HER2+ molecular subtype is one of the most aggressive subtypes; its treatment includes neoadjuvant chemotherapy and the use of a HER2 antibody. Some patients develop resistance despite positive results obtained using this therapeutic strategy. OBJECTIVE: To identify prognostic markers for treatment and survival in HER2+ patients. METHODS: Patients treated with neoadjuvant chemotherapy were assigned to sensitive and resistant groups based on their treatment response. Differentially expressed genes (DEGs) were identified using RNA-seq analysis. KEGG pathway, gene ontology, and interactome analyses were performed for all DEGs. An enrichment analysis Gene set enrichment analysis was performed. All DEGs were analyzed for overall (OS) and disease-free survival (DFS). RESULTS: A total of 94 DEGs were related to treatment resistance. Survival analysis showed that 12 genes (ATF6B, DHRS13, DIRAS1, ERAL1, GRIN2B, L1CAM, IRX3, PRTFDC1, PBX2, S100B, SLC9A3R2, and TNXB) were good predictors of disease-free survival, and eight genes (GNG4, IL22RA2, MICA, S100B, SERPINF2, HLA-A, DIRAS1, and TNXB) were good predictors of overall survival (OS). CONCLUSION: We highlighted a molecular expression signature that can differentiate the treatment response, overall survival, and DFS of patients with HER2+ breast cancer.
ABSTRACT
Worldwide breast cancer ranks first in mortality and incidence rates in women over 20 years old. Rather than one disease, breast cancer is a heterogeneous group of diseases that express distinct molecular profiles. Neoadjuvant chemotherapy is an important therapeutic strategy for breast cancer patients independently of their molecular subtype, with the drawback of resistance development. In addition, chemotherapy has adverse effects that combined with resistance could contribute to lower overall survival. Although great efforts have been made to find diagnostic and prognostic biomarkers for breast cancer and for response to targeted and immune therapy for this pathology, little has been explored regarding biomarkers of response to anthracyclines and taxanes based neoadjuvant chemotherapy. This work aimed to evaluate the molecular profile of patients who received neoadjuvant chemotherapy to identify differentially expressed genes (DEGs) that could be used as biomarkers of chemotherapy response and overall survival. Breast cancer patients who were candidates for neoadjuvant chemotherapy were enrolled in this study. After treatment and according to their pathological response, they were assigned as sensitive or resistant. To evaluate DEGs, Gene Ontology, Kyoto Encyclopedia Gene and Genome (KEGG), and protein-protein interactions, RNA-seq information from all patients was obtained by next-generation sequencing. A total of 1985 DEGs were found, and KEGG analysis indicated a great number of DEGs in metabolic pathways, pathways in cancer, cytokine-cytokine receptor interactions, and neuroactive ligand-receptor interactions. A selection of 73 DEGs was used further for an analysis of overall survival using the METABRIC study and the ductal carcinoma dataset of The Cancer Genome Atlas (TCGA) database. Nine DEGs correlated with overall survival, of which the subexpression of C1QTNF3, CTF1, OLFML3, PLA2R1, PODN, KRT15, HLA-A, and the overexpression of TUBB and TCP1 were found in resistant patients and related to patients with lower overall survival.
Subject(s)
Breast Neoplasms/genetics , Drug Resistance, Neoplasm/genetics , Gene Expression Profiling , Gene Expression Regulation, Neoplastic , Transcriptome , Biomarkers, Tumor , Breast Neoplasms/diagnosis , Breast Neoplasms/drug therapy , Breast Neoplasms/mortality , Cell Line, Tumor , Clinical Decision-Making , Computational Biology , Disease Management , Female , Gene Expression Regulation, Neoplastic/drug effects , Gene Ontology , Humans , Neoadjuvant Therapy , Prognosis , Protein Interaction MappingABSTRACT
BACKGROUND: The Official Mexican Norm for the prevention, treatment and control of Cervical Cancer (CC) indicates that the Papanicolau (Pap) is the procedure for the detection of this neoplasia; therefore, it is of interest to know the prevalence of suspected cases by this technique in Mexican population. In this study, we show the diagnosed cases in the State of Jalisco, México. METHODS: A retrospective study was made to the samples that arrived for their analysis to the Laboratorio Regional de Citología Exfoliativa (LARCE), of the Instituto Mexicano del Seguro Social (IMSS) in Guadalajara, Jalisco. We considered all cases from January 2010 to December 2012. RESULTS: We analyzed 188 095 cases, from which 5.3 % had a diagnosis of low dysplasia, 0.18 % of moderated dysplasia and 0.05 % of high dysplasia. Microinvasive and invasive cancer showed a low frequency (0.03 %). CONCLUSIONS: The frequency of abnormal findings identified by vaginal cervical cytology is relatively low. The number of inadequate and limited samples for cytological assessment is high; there is a high proportion of women attending for the first time in life to cytology evaluation in older age groups.
Introducción: La Norma Oficial Mexicana para la prevención, tratamiento y control del Cáncer Cérvico Uterino (CaCU) indica que el Papanicolaou (Pap) es el procedimiento de elección para la detección oportuna de esta neoplasia, por lo que es de interés conocer la prevalencia de casos tamizados mediante esta técnica en la población mexicana. En la presente investigación se muestran los casos que se identificaron como sospecha para CaCU por tamizaje en el estado de Jalisco, México. Métodos: se realizó un estudio retrospectivo de las muestras que llegaron para su análisis al Laboratorio Regional de Citología Exfoliativa (LARCE) del Instituto Mexicano del Seguro Social (IMSS) en Guadalajara, Jalisco. Se consideraron todos los casos de enero de 2010 a diciembre de 2012. Resultados: se analizaron 188 095 casos, de los cuales el 5.3 % se reportaron con sospecha de displasia leve, el 0.18 % de displasia moderada y el 0.05 % de displasia grave. En cáncer microinvasor e invasor se observó una baja frecuencia (0.03 %). Conclusiones: la frecuencia de hallazgos anormales identificados por citología cervicovaginal es relativamente baja. El número de muestras inadecuadas más limitadas para valoración citológica es alto; existe una elevada proporción de mujeres que asisten por primera vez en la vida a estudio citológico en grupos de edad avanzados.