Barrón-Gallardo Carlos A, Garcia-Chagollán Mariel, Morán-Mendoza Andres J, Delgadillo-Cristerna Raul, Martínez-Silva María G, Villaseñor-García María M, Aguilar-Lemarroy Adriana, Jave-Suárez Luis F
Programa de Doctorado en Ciencias Biomédicas, Centro Universitario de Ciencias de La Salud, Universidad de Guadalajara, Guadalajara, Mexico.
Instituto de Investigación en Ciencias Biomédicas (IICB), Centro Universitario de Ciencias de La Salud, Universidad de Guadalajara, Guadalajara, Mexico.
Front Genet. 2022 Oct 21;13:991706. doi: 10.3389/fgene.2022.991706. eCollection 2022.
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.
To identify prognostic markers for treatment and survival in HER2+ patients.
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).
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).
We highlighted a molecular expression signature that can differentiate the treatment response, overall survival, and DFS of patients with HER2+ breast cancer.
在全球女性中，乳腺癌的死亡率和发病率位居首位。HER2+分子亚型是最具侵袭性的亚型之一；其治疗包括新辅助化疗和使用HER2抗体。尽管采用这种治疗策略取得了阳性结果，但仍有一些患者产生耐药性。
确定HER2+患者治疗和生存的预后标志物。
根据新辅助化疗患者的治疗反应将其分为敏感组和耐药组。使用RNA测序分析确定差异表达基因（DEG）。对所有DEG进行KEGG通路、基因本体和相互作用组分析。进行富集分析基因集富集分析。分析所有DEG的总生存期（OS）和无病生存期（DFS）。
共有94个DEG与治疗耐药相关。生存分析表明，12个基因（ATF6B、DHRS13、DIRAS1、ERAL1、GRIN2B、L1CAM、IRX3、PRTFDC1、PBX2、S100B、SLC9A3R2和TNXB）是无病生存期的良好预测指标，8个基因（GNG4、IL22RA2、MICA、S100B、SERPINF2、HLA-A、DIRAS1和TNXB）是总生存期（OS）的良好预测指标。
我们突出了一种分子表达特征，它可以区分HER2+乳腺癌患者的治疗反应、总生存期和DFS。
