Alizadeh Mahdi, Salimi Mahdieh, Soheila Soheili Zahra
Department of Medical Genetics, Institute of Medical Biotechnology, National Institute of Genetic Engineering and Biotechnology (NIGEB), Tehran, Iran.
Department of Molecular Medicine, Institute of Medical Biotechnology, National Institute of Genetic Engineering and Biotechnology (NIGEB), Tehran, Iran.
Iran J Biotechnol. 2025 Apr 1;23(2):e4051. doi: 10.30498/ijb.2025.497569.4051. eCollection 2025 Apr.
Breast cancer remains a leading cause of cancer-related mortality among women, highlighting the urgent need for reliable biomarkers that can aid in prognosis and therapeutic stratification.
This study aimed to evaluate the RNA expression levels of four specific genes-, , , and -in breast cancer tumors compared to adjacent normal tissues, and to assess their prognostic significance in relation to clinical parameters and recurrence-free survival.
The RNA expression levels of , , , and were examined using SYBR Green real-time PCR. Gene expression data were correlated with clinical parameters, including disease stage, lymph node involvement, and triple-negative status. Survival analysis was conducted to evaluate the prognostic significance of these genes concerning recurrence within five years post-diagnosis, with median expression cutoffs established for each gene and the overall median for the panel. Kaplan-Meier survival analysis was employed to assess the relationship between gene expression and recurrence-free survival, calculating hazard ratios (HR) for each gene and the combined panel. Additionally, the Reactome database was analyzed to identify biological pathways associated with these genes.
All four genes demonstrated significantly higher expression levels in breast cancer samples, correlating with advanced disease stages, lymph node involvement, and triple-negative breast cancer status. expression was notably associated with estrogen receptor (ER) and progesterone receptor (PR) positivity, while expression correlated with ER negativity. Survival analysis revealed that 6 out of 40 patients expired within five years. Kaplan-Meier analysis indicated that higher expression levels of (HR 14.80, p=0.0015), (HR 9.259, p=0.0071), (HR 12.49, p=0.0027), and (HR 7.315, p=0.0158) were significantly associated with reduced recurrence-free survival. The hazard ratio for the combined gene panel was 15.367 (p<0.0001). Reactome analysis revealed that these genes are involved in critical biological pathways, including actin folding by CCT TriC and TP53 regulation of G1 cell cycle arrest.
Our findings suggest that this four-gene panel holds significant promise as a robust prognostic tool for breast cancer survival. This research paves the way for further investigations into targeted therapies and personalized medicine approaches in the management of breast cancer.
乳腺癌仍是女性癌症相关死亡的主要原因，这凸显了对有助于预后和治疗分层的可靠生物标志物的迫切需求。
本研究旨在评估四种特定基因（、、和）在乳腺癌肿瘤与相邻正常组织中的RNA表达水平，并评估它们与临床参数及无复发生存率相关的预后意义。
使用SYBR Green实时定量PCR检测、、、的RNA表达水平。基因表达数据与临床参数相关联，包括疾病分期、淋巴结受累情况和三阴性状态。进行生存分析以评估这些基因对诊断后五年内复发的预后意义，为每个基因及该基因组合确定中位数表达阈值。采用Kaplan-Meier生存分析评估基因表达与无复发生存率之间的关系，计算每个基因及组合基因的风险比（HR）。此外，分析Reactome数据库以鉴定与这些基因相关的生物学途径。
所有四个基因在乳腺癌样本中的表达水平均显著更高，与疾病晚期、淋巴结受累和三阴性乳腺癌状态相关。的表达与雌激素受体（ER）和孕激素受体（PR）阳性显著相关，而的表达与ER阴性相关。生存分析显示，40名患者中有6人在五年内死亡。Kaplan-Meier分析表明，较高的（HR 14.80，p = 0.0015）、（HR 9.259，p = 0.0071）、（HR 12.49，p = 0.0027）和（HR 7.315，p = 0.0158）表达水平与无复发生存率降低显著相关。组合基因的风险比为15.367（p < 0.0001）。Reactome分析表明，这些基因参与关键生物学途径，包括CCT TriC介导的肌动蛋白折叠和TP53对G1期细胞周期停滞的调控。
我们的研究结果表明，这个四基因组合有望成为预测乳腺癌生存的有力工具。本研究为进一步研究乳腺癌治疗中的靶向治疗和个性化医疗方法铺平了道路。
