Medizinische Klinik V, Universitätsklinikum Heidelberg, Germany.
Clin Cancer Res. 2011 Dec 1;17(23):7240-7. doi: 10.1158/1078-0432.CCR-11-1628. Epub 2011 Oct 10.
Multiple myeloma is an incurable malignant plasma cell disease characterized by survival ranging from several months to more than 15 years. Assessment of risk and underlying molecular heterogeneity can be excellently done by gene expression profiling (GEP), but its way into clinical routine is hampered by the lack of an appropriate reporting tool and the integration with other prognostic factors into a single "meta" risk stratification.
The GEP-report (GEP-R) was built as an open-source software developed in R for gene expression reporting in clinical practice using Affymetrix microarrays. GEP-R processes new samples by applying a documentation-by-value strategy to the raw data to be able to assign thresholds and grouping algorithms defined on a reference cohort of 262 patients with multiple myeloma. Furthermore, we integrated expression-based and conventional prognostic factors within one risk stratification (HM-metascore).
The GEP-R comprises (i) quality control, (ii) sample identity control, (iii) biologic classification, (iv) risk stratification, and (v) assessment of target genes. The resulting HM-metascore is defined as the sum over the weighted factors gene expression-based risk-assessment (UAMS-, IFM-score), proliferation, International Staging System (ISS) stage, t(4;14), and expression of prognostic target genes (AURKA, IGF1R) for which clinical grade inhibitors exist. The HM-score delineates three significantly different groups of 13.1%, 72.1%, and 14.7% of patients with a 6-year survival rate of 89.3%, 60.6%, and 18.6%, respectively.
GEP reporting allows prospective assessment of risk and target gene expression and integration of current prognostic factors in clinical routine, being customizable about novel parameters or other cancer entities.
多发性骨髓瘤是一种无法治愈的恶性浆细胞疾病，其生存时间从数月到 15 年以上不等。通过基因表达谱（GEP）可以很好地评估风险和潜在的分子异质性，但由于缺乏合适的报告工具以及将其他预后因素整合到单一的“综合”风险分层中，其在临床常规中的应用受到阻碍。
GEP 报告（GEP-R）是一个开源软件，使用 R 语言开发，用于在临床实践中使用 Affymetrix 微阵列进行基因表达报告。GEP-R 通过对原始数据应用按值记录的文档策略来处理新样本，以便能够为 262 名多发性骨髓瘤患者的参考队列定义阈值和分组算法。此外，我们在一个风险分层（HM-metascore）中整合了基于表达的和常规的预后因素。
GEP-R 包括 (i) 质量控制，(ii) 样本身份控制，(iii) 生物学分类，(iv) 风险分层，和 (v) 靶基因评估。所得的 HM-metascore 定义为基于基因表达的风险评估（UAMS-、IFM 评分）、增殖、国际分期系统（ISS）分期、t(4;14)和存在临床级抑制剂的预后靶基因（AURKA、IGF1R）的加权因素的总和。HM 评分将患者分为三个明显不同的组，分别为 13.1%、72.1%和 14.7%，6 年生存率分别为 89.3%、60.6%和 18.6%。
GEP 报告允许在临床常规中前瞻性评估风险和靶基因表达，并整合当前的预后因素，同时可以定制新的参数或其他癌症实体。
