microRNA profiling and clinical outcomes in human osteosarcoma (biopsies)

Osteosarcoma is a malignancy with variable outcomes that are not tightly aligned with chemotherapy response. Previous work has suggested a possible role for microRNAs (miRNAs) in determining the susceptibility of osteosarcomas to treatment but formal miRNA-based outcome models have not been reported. Formalin-fixed, paraffin-embedded (FFPE) specimens may be a unique approach for such studies in a rare malignancy. We used supervised principal components analysis and logistic regression to study survival and chemoresponse endpoints, and miRNA activity and gene set analysis algorithms to study miRNA regulatory networks using mRNA data. Our study also creates a paradigm for FFPE-based miRNA clinical biomarker research in rare tumors. 65 unique diagnostic biopsy specimens were profiled. Samples with paired surgical resection specimens (not included in this submission) are denoted in the Sample 'characteristics' field.

骨肉瘤是一类预后异质性显著的恶性肿瘤，其临床预后与化疗应答程度并无紧密关联。既往研究已提示微小RNA（miRNAs）可能在调控骨肉瘤治疗易感性方面发挥潜在作用，但目前尚未见基于miRNA的正式预后模型相关报道。福尔马林固定石蜡包埋（FFPE）样本或许是开展此类罕见恶性肿瘤相关研究的独特实验材料。本研究采用监督主成分分析与逻辑回归模型，针对生存结局与化疗应答终点开展分析；同时借助miRNA活性及基因集分析算法，结合信使RNA（mRNA）数据探究miRNA调控网络。本研究同时为罕见肿瘤领域内基于FFPE样本的miRNA临床生物标志物研究提供了标准化研究范式。本研究共完成65例独立诊断活检标本的表达谱分析。样本的"特征"字段中标记了带有配对手术切除标本的样本（此类标本未纳入本次提交范围）。