Ferrick-Kiddie Elizabeth A, Dommaraju Sriya, Yao Jun, Smith Christopher W, Wang Xiaoping, Woodward Wendy A, Ueno Naoto T, Krishnamurthy Savitri, Lambowitz Alan M
Departments of Molecular Biosciences and Oncology, University of Texas at Austin, Austin, TX 78712.
Cancer Biology Program and Translational Clinical Research Program, University of Hawai'i Cancer Center, Honolulu, HI 96813.
medRxiv. 2025 Aug 21:2025.08.19.25333925. doi: 10.1101/2025.08.19.25333925.
Previous TGIRT-seq analysis of RNAs in Inflammatory Breast Cancer (IBC) patient tumors, peripheral blood mononuclear cells (PBMCs) and plasma identified a short T-cell receptor mRNA fragment () as a potential IBC biomarker that was detected in plasma samples from IBC patients but not patients with non-inflammatory breast cancer or healthy donors. Here, we traced the origin of this RNA fragment to IBC patient PBMCs and used a high-throughput RT-PCR/Cas12a assay with larger numbers of samples to confirm its prevalence in IBC patient PBMCs. Detection of this RNA was enhanced by T4 polynucleotide kinase treatment, indicating the presence of a 2',3'-cyclic phosphate. Analysis of previous TGIRT-seq datasets revealed gene expression differences in IBC patient PBMCs that could contribute to RNA prevalence in IBC patient PBMCs and plasma. Our results support the identification of the RNA fragment as a novel, readily detectable blood-based RNA biomarker derived from IBC-patient immune cells, addressing a major unmet need for diagnosing IBC.
先前对炎性乳腺癌（IBC）患者肿瘤、外周血单个核细胞（PBMC）和血浆中的RNA进行的TGIRT-seq分析，鉴定出一个短的T细胞受体mRNA片段（）作为潜在的IBC生物标志物，该片段在IBC患者的血浆样本中被检测到，但在非炎性乳腺癌患者或健康供体的血浆样本中未被检测到。在此，我们追踪了这个RNA片段的来源至IBC患者的PBMC，并使用高通量RT-PCR/Cas12a检测法对更多样本进行检测，以确认其在IBC患者PBMC中的普遍性。通过T4多核苷酸激酶处理增强了对该RNA的检测，表明存在2'，3'-环磷酸酯。对先前TGIRT-seq数据集的分析揭示了IBC患者PBMC中的基因表达差异，这可能导致IBC患者PBMC和血浆中RNA的普遍性。我们的结果支持将该RNA片段鉴定为一种源自IBC患者免疫细胞的新型、易于检测的血液RNA生物标志物，满足了诊断IBC的一项主要未满足需求。
