Muñoz Juan P, Soto-Jiménez Diego, Calaf Gloria M
Laboratorio de Bioquímica, Departamento de Química, Facultad de Ciencias, Universidad de Tarapacá, Arica 1000007, Chile.
Instituto de Alta Investigación, Universidad de Tarapacá, Arica 1000000, Chile.
Biomedicines. 2024 Aug 2;12(8):1732. doi: 10.3390/biomedicines12081732.
Breast cancer (BRCA) remains a significant global health challenge due to its prevalence and lethality, exacerbated by the development of resistance to conventional therapies. Therefore, understanding the molecular mechanisms underpinning chemoresistance is crucial for improving therapeutic outcomes. Human deoxycytidine triphosphate pyrophosphatase 1 (DCTPP1) has emerged as a key player in various cancers, including BRCA. DCTPP1, involved in nucleotide metabolism and maintenance of genomic stability, has been linked to cancer cell proliferation, survival, and drug resistance. This study evaluates the role of DCTPP1 in BRCA prognosis and chemotherapy response. Data from the Cancer Genome Atlas Program (TCGA), Genotype-Tissue Expression (GTEx), and Gene Expression Omnibus (GEO) repositories, analyzed using GEPIA and Kaplan-Meier Plotter, indicate that high DCTPP1 expression correlates with poorer overall survival and increased resistance to chemotherapy in BRCA patients. Further analysis reveals that gene expression is up-regulated in non-responders to chemotherapy, particularly in estrogen receptor (ER)-positive, luminal A subtype patients, with significant predictive power. Additionally, in vitro studies show that gene expression increases in response to 5-fluorouracil and doxorubicin treatments in luminal A BRCA cell lines, suggesting a hypothetical role in chemoresistance. These findings highlight DCTPP1 as a potential biomarker for predicting chemotherapy response and as a therapeutic target to enhance chemotherapy efficacy in BRCA patients.
由于乳腺癌（BRCA）的患病率和致死率，它仍然是一个重大的全球健康挑战，而对传统疗法耐药性的发展则加剧了这一挑战。因此，了解化疗耐药背后的分子机制对于改善治疗效果至关重要。人类脱氧胞苷三磷酸焦磷酸酶1（DCTPP1）已成为包括BRCA在内的各种癌症中的关键因素。DCTPP1参与核苷酸代谢和基因组稳定性的维持，与癌细胞增殖、存活及耐药性有关。本研究评估DCTPP1在BRCA预后和化疗反应中的作用。使用GEPIA和Kaplan-Meier Plotter分析来自癌症基因组图谱计划（TCGA）、基因型-组织表达（GTEx）和基因表达综合数据库（GEO）的数据，结果表明，DCTPP1高表达与BRCA患者较差的总生存率和化疗耐药性增加相关。进一步分析显示，该基因在化疗无反应者中表达上调，尤其是在雌激素受体（ER）阳性的管腔A型亚型患者中，具有显著的预测能力。此外，体外研究表明，在管腔A型BRCA细胞系中，该基因表达在5-氟尿嘧啶和阿霉素处理后增加，提示其在化疗耐药中的假设作用。这些发现突出了DCTPP1作为预测化疗反应的潜在生物标志物以及作为提高BRCA患者化疗疗效的治疗靶点的作用。
