Division of Medical Oncology, University of Colorado Anschutz Medical Campus, Aurora, Colorado; Division of Thoracic Surgery, Department of Surgery, Kindai University Faculty of Medicine, Osaka-Sayama, Japan.
Division of Medical Oncology, University of Colorado Anschutz Medical Campus, Aurora, Colorado.
J Thorac Oncol. 2018 Oct;13(10):1496-1507. doi: 10.1016/j.jtho.2018.05.039. Epub 2018 Jun 19.
Data regarding the pre-treatment intertumor heterogeneity of potential biomarkers in advanced-stage lung cancers is limited. A finding of such heterogeneity between primary and metastatic lesions would prove valuable to determine if a metastatic lesion can be a surrogate for the primary tumor, as more biomarkers will likely be used in the future to inform treatment decisions.
We performed RNA sequencing to analyze intertumor heterogeneity in 30 specimens (primary tumors, intrathoracic, and extrathoracic metastatic lesions) obtained from five treatment-naïve lung cancer patients.
The global unsupervised clustering analysis showed that the lesions clustered at the individual patient level rather than on the metastatic sites, suggesting that the characteristics of specific tumor cells have a greater impact on the gene expression signature than the microenvironment in which the metastasis develops. The mutational and transcriptional data highlight the presence of intertumor heterogeneity showing that the primary tumors are usually distinct from metastatic lesions. Through a comparison between metastatic lesions and the primary tumors, we observed that pathways related to cell proliferation were upregulated, whereas immune-related pathways were downregulated in metastatic lesions.
These data not only provide insight into the evolution of lung cancers, but also imply possibilities and limitations of biomarker-based treatment in lung cancers.
关于晚期肺癌潜在生物标志物治疗前肿瘤间异质性的数据有限。如果转移病灶可以作为原发性肿瘤的替代物，那么原发性和转移性病变之间存在这种异质性的发现将非常有价值，因为未来可能会使用更多的生物标志物来为治疗决策提供信息。
我们对 5 名未经治疗的肺癌患者的 30 个标本（原发性肿瘤、胸内和胸外转移病灶）进行了 RNA 测序分析，以研究肿瘤间异质性。
全局无监督聚类分析表明，病变按个体患者水平聚类，而不是按转移部位聚类，这表明特定肿瘤细胞的特征对基因表达特征的影响大于转移发展的微环境。突变和转录数据突出了肿瘤间异质性的存在，表明原发性肿瘤通常与转移性病变不同。通过比较转移病灶和原发性肿瘤，我们观察到与细胞增殖相关的通路上调，而免疫相关通路在转移病灶中下调。
这些数据不仅深入了解了肺癌的演变，还暗示了基于生物标志物的治疗在肺癌中的可能性和局限性。
