软组织肉瘤组织学亚型miRNA综合表达分析

R. Tsuchiya, Yuki Yoshimatsu, Naoto Tsuchiya, S. Ohtori, A. Kawai, T. Kondo
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摘要

肉瘤是一种罕见的间充质恶性肿瘤,包括50多种组织学亚型。由于肉瘤的罕见性和多样性,其鉴别诊断是困难的,并且仍然需要生物标志物来支持病理诊断。微rna (miRNAs)是一种小的非编码rna,可调节肿瘤的行为,如侵袭和转移。mirna的表达模式反映了恶性肿瘤的起源,被认为是候选的生物标志物。为了了解这些组织学亚型的分子背景,我们研究了8种亚型89个肿瘤组织中的miRNA表达。基于miRNA表达值的各肉瘤亚型间的相关系数大多大于0.7,反映了肉瘤亚型间质起源的共性。分层聚类和主成分分析结果显示,染色体易位的3种肉瘤(即皮肤纤维突肉瘤、黏液样脂肪肉瘤和滑膜肉瘤)可根据其组织学亚型进行分组,而5种复杂核型的肉瘤(即黏液纤维肉瘤、恶性周围神经鞘肿瘤、未分化多形性肉瘤、去分化脂肪肉瘤和多形性脂肪肉瘤)则不能进行分组。值得注意的是,与具有复杂核型的肉瘤相比,染色体易位肉瘤中表达模式为组织学亚型特有的mirna的数量具有统计学意义。因此,可以得出结论,组织学亚型特有的mirna是肉瘤鉴别诊断的候选生物标志物,特别是那些染色体易位的肉瘤。
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Comprehensive miRNA expression analysis for histological subtypes of soft tissue sarcoma
Sarcoma is a rare mesenchymal malignancy that comprises more than 50 histological subtypes. Because of the rarity and diversity of sarcomas, their differential diagnosis is difficult, and there is still a need for biomarkers to support pathological diagnoses. Micro RNAs (miRNAs) are small noncoding RNAs that regulate the behavior of tumors, such as invasion and metastasis. The expression patterns of miRNAs reflect the origin of malignancy and are considered to be candidate biomarkers. To understand the molecular background of those histological subtypes, we investigated the miRNA expression in 89 tumor tissues of eight subtypes. The correlation coefficients between each sarcoma subtype on the basis of miRNA expression values were mostly higher than 0.7, reflecting the common mesenchymal origin. By contrast, hierarchical clustering and principal component analysis showed that three types of sarcoma with chromosomal translocation (i.e., dermatofibrosarcoma protuberans, myxoid liposarcoma, and synovial sarcoma) were grouped according to their histological subtypes, whereas five types with complex karyotypes (i.e., myxofibrosarcoma, malignant peripheral nerve sheath tumor, undifferentiated pleomorphic sarcoma, dedifferentiated liposarcoma, and pleomorphic liposarcoma) were not. Notably, the number of miRNAs whose expression pattern was unique to histological subtypes with statistical significance was higher in sarcomas with chromosome translocation than in those with complex karyotypes. Hence, it can be concluded that the miRNAs unique to histological subtypes are candidate biomarkers for the differential diagnosis of sarcomas, particularly in those with chromosomal translocation.
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