Department of Pathology, National University Hospital, National University Health System, Singapore 119074, Singapore.
MiRXES Lab, Singapore 138623, Singapore.
Int J Mol Sci. 2022 Jul 15;23(14):7804. doi: 10.3390/ijms23147804.
Adipocytic tumors are the most common subtype of soft tissue tumors. In current clinical practice, distinguishing benign lipomas from well-differentiated liposarcomas (WDLPS), as well as dedifferentiated liposarcomas (DDLPS) from their morphologic mimics, remains a significant diagnostic challenge. This is especially so when examining small biopsy samples and without the aid of additional ancillary tests. Recognizing the important role that microRNAs (miRNAs) play in tumorigenesis and their potential utility in tumor classification, we analyzed routine clinical tissue samples of benign and malignant lipomatous tumors, as well as other sarcoma mimics, to identify distinguishing miRNA-based signatures that can aid in the differential diagnosis of these entities. We discovered a 6-miRNA signature that separated lipomas from WDLPS with high confidence (AUC of 0.963), as well as a separate 6-miRNA signature that distinguished DDLPS from their more aggressive histologic mimics (AUC of 0.740). Functional enrichment analysis unveiled possible mechanistic involvement of these predictive miRNAs in adipocytic cancer-related biological processes and pathways such as PI3K/AKT/mTOR and MAPK signaling, further supporting the relevance of these miRNAs as biomarkers for adipocytic tumors. Our results demonstrate that miRNA expression profiling may potentially be used as an adjunctive tool for the diagnosis of benign and malignant adipocytic tumors. Further validation studies are warranted.
脂肪性肿瘤是软组织肿瘤中最常见的亚型。在当前的临床实践中，区分良性脂肪瘤与分化良好的脂肪肉瘤（WDLPS）以及去分化脂肪肉瘤（DDLPS）与其形态学模拟物仍然是一个重大的诊断挑战。在检查小的活检样本且没有辅助附加测试的情况下尤其如此。鉴于 microRNAs（miRNAs）在肿瘤发生中的重要作用及其在肿瘤分类中的潜在应用价值，我们分析了良性和恶性脂肪性肿瘤以及其他肉瘤模拟物的常规临床组织样本，以确定有助于这些实体的鉴别诊断的区分 miRNA 特征。我们发现了一个 6- miRNA 特征，可以高度置信地区分脂肪瘤与 WDLPS（AUC 为 0.963），以及另一个区分 DDLPS 与其更具侵袭性的组织学模拟物的 6- miRNA 特征（AUC 为 0.740）。功能富集分析揭示了这些预测性 miRNA 可能参与脂肪性癌症相关生物学过程和途径（如 PI3K/AKT/mTOR 和 MAPK 信号通路）的潜在机制，进一步支持这些 miRNA 作为脂肪性肿瘤生物标志物的相关性。我们的研究结果表明，miRNA 表达谱分析可能潜在地用作良性和恶性脂肪性肿瘤诊断的辅助工具。需要进一步的验证研究。
