Tripathi Shyam, Mathaiyan Jayanthi, Kayal Smita, Nachiappa Ganesh Rajesh
Department of Pharmacology, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, IND.
Department of Medical Oncology, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, IND.
Cureus. 2024 May 2;16(5):e59553. doi: 10.7759/cureus.59553. eCollection 2024 May.
MicroRNAs (miRNAs) are known to play an important role in cancer cell proliferation, susceptibility of cancer cells to chemotherapy, and patient survival. Identifying miRNAs that can predict response to chemotherapy in locally advanced breast cancer (LABC), the most common variant, can help to choose appropriate drug regimens to suit the epigenetic profile of individual patients.
To investigate the expression of the differentially expressed miRNAs identified by next-generation sequencing from a pilot study involving cases and controls, in peripheral blood mononuclear cells (PBMC) of patients with LABC during the course of neoadjuvant chemotherapy (NAC) and determine their role in response to chemotherapy.
This study included 30 newly diagnosed LABC patients. Peripheral blood from every participant was collected before the start of chemotherapy, at the end of the third cycle, and at the end of the seventh cycle of NAC. Based on the results of a pilot study in a similar population with suitable controls, four differentially expressed miRNAs namely miR-24-2, miR-192-5p, miR-3609, and miR-664b-3p were considered to be validated in this study. The expression of these four miRNAs was examined by qRT-PCR, and their association with response to chemotherapy was analyzed.
A significant change in the expression of miR-192-5p was found in responders (p = 0.001) over a period of seven cycles and the difference between the expression of miR-24-2 from baseline to the seventh cycle of NAC was higher in responders while compared to the non-responders (p < 0.05).
miR-192-5p and miR-24-2 were identified as predictive biomarkers for response to NAC in south Indian patients with LABC.
已知微小RNA(miRNA)在癌细胞增殖、癌细胞对化疗的敏感性以及患者生存中发挥重要作用。在最常见的局部晚期乳腺癌(LABC)中,鉴定能够预测化疗反应的miRNA,有助于选择适合个体患者表观遗传特征的合适药物方案。
研究在一项涉及病例和对照的初步研究中通过下一代测序鉴定出的差异表达miRNA,在新辅助化疗(NAC)过程中LABC患者外周血单个核细胞(PBMC)中的表达情况,并确定它们在化疗反应中的作用。
本研究纳入30例新诊断的LABC患者。在化疗开始前、第三个周期结束时以及NAC第七个周期结束时,收集每位参与者的外周血。基于在具有合适对照的相似人群中的初步研究结果,本研究考虑验证四个差异表达的miRNA,即miR-24-2、miR-192-5p、miR-3609和miR-664b-3p。通过qRT-PCR检测这四个miRNA的表达,并分析它们与化疗反应的相关性。
在七个周期内,反应者中miR-192-5p的表达有显著变化(p = 0.001),与无反应者相比,反应者从基线到NAC第七个周期miR-24-2的表达差异更高(p < 0.05)。
miR-192-5p和miR-24-2被确定为印度南部LABC患者对NAC反应的预测生物标志物。