Peripheral Immune Cell Gene Expression Predicts Survival of Patients with Non-Small Cell Lung Cancer

Prediction of cancer recurrence in patients with non-small cell lung cancer (NSCLC) currently relies on the assessment of clinical characteristics including age, tumor stage, and smoking history. A better prediction of early stage cancer patients with poorer survival and late stage patients with better survival is needed to design patient-tailored treatment protocols. We analyzed gene expression in RNA from peripheral blood mononuclear cells (PBMC) of NSCLC patients to identify signatures predictive of overall patient survival. We find that PBMC gene expression patterns from NSCLC patients, like patterns from tumors, have information predictive of patient outcomes. We identify and validate a 26 gene prognostic panel that is independent of clinical stage. Many additional prognostic genes are specific to myeloid cells and are more highly expressed in patients with shorter survival. We also observe that significant numbers of prognostic genes change expression levels in PBMC collected after tumor resection. These post-surgery gene expression profiles may provide a means to re-evaluate prognosis over time. These studies further suggest that patient outcomes are not solely determined by tumor gene expression profiles but can also be influenced by the immune response as reflected in peripheral immune cells.当前，非小细胞肺癌（non-small cell lung cancer, NSCLC）患者的癌症复发预测主要依赖于年龄、肿瘤分期、吸烟史等临床特征的评估。目前亟需更精准地预测生存预后较差的早期癌症患者，以及生存预后较好的晚期癌症患者，以制定个体化治疗方案。本研究分析了非小细胞肺癌患者外周血单个核细胞（peripheral blood mononuclear cells, PBMC）的RNA基因表达谱，以筛选可预测患者总生存期的特征基因。研究发现，非小细胞肺癌患者外周血单个核细胞的基因表达模式与肿瘤组织的基因表达模式一样，均携带有可预测患者转归的信息。本研究鉴定并验证了一个独立于临床分期的26基因预后特征组合。此外，大量额外的预后基因特异性表达于髓系细胞，且在生存周期较短的患者中表达水平更高。本研究还观察到，肿瘤切除术后采集的外周血单个核细胞中，大量预后基因的表达水平发生了显著变化。这些术后基因表达谱或许可作为一种手段，用于随时间推移重新评估患者的预后情况。本研究进一步表明，患者的临床转归并非仅由肿瘤基因表达谱决定，同时也会受到外周免疫细胞所反映的免疫应答状态的影响。