Prospective validation of ORACLE, a clonal expression biomarker associated with survival of patients with lung adenocarcinoma.

IF 23.5 1区医学 Q1 ONCOLOGY

Nature cancer Pub Date : 2025-01-09 DOI:10.1038/s43018-024-00883-1

Dhruva Biswas, Yun-Hsin Liu, Javier Herrero, Yin Wu, David A Moore, Takahiro Karasaki, Kristiana Grigoriadis, Wei-Ting Lu, Selvaraju Veeriah, Cristina Naceur-Lombardelli, Neil Magno, Sophia Ward, Alexander M Frankell, Mark S Hill, Emma Colliver, Sophie de Carné Trécesson, Philip East, Aman Malhi, Daniel M Snell, Olga O'Neill, Daniel Leonce, Johanna Mattsson, Amanda Lindberg, Patrick Micke, Judit Moldvay, Zsolt Megyesfalvi, Balazs Dome, János Fillinger, Jerome Nicod, Julian Downward, Zoltan Szallasi, Allan Hackshaw, Mariam Jamal-Hanjani, Nnennaya Kanu, Nicolai J Birkbak, Charles Swanton

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引用次数: 0

Abstract

Human tumors are diverse in their natural history and response to treatment, which in part results from genetic and transcriptomic heterogeneity. In clinical practice, single-site needle biopsies are used to sample this diversity, but cancer biomarkers may be confounded by spatiogenomic heterogeneity within individual tumors. Here we investigate clonally expressed genes as a solution to the sampling bias problem by analyzing multiregion whole-exome and RNA sequencing data for 450 tumor regions from 184 patients with lung adenocarcinoma in the TRACERx study. We prospectively validate the survival association of a clonal expression biomarker, Outcome Risk Associated Clonal Lung Expression (ORACLE), in combination with clinicopathological risk factors, and in stage I disease. We expand our mechanistic understanding, discovering that clonal transcriptional signals are detectable before tissue invasion, act as a molecular fingerprint for lethal metastatic clones and predict chemotherapy sensitivity. Lastly, we find that ORACLE summarizes the prognostic information encoded by genetic evolutionary measures, including chromosomal instability, as a concise 23-transcript assay.

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来源期刊

Nature cancer Medicine-Oncology

CiteScore

31.10

自引率

1.80%

发文量

129

期刊介绍： Cancer is a devastating disease responsible for millions of deaths worldwide. However, many of these deaths could be prevented with improved prevention and treatment strategies. To achieve this, it is crucial to focus on accurate diagnosis, effective treatment methods, and understanding the socioeconomic factors that influence cancer rates. Nature Cancer aims to serve as a unique platform for sharing the latest advancements in cancer research across various scientific fields, encompassing life sciences, physical sciences, applied sciences, and social sciences. The journal is particularly interested in fundamental research that enhances our understanding of tumor development and progression, as well as research that translates this knowledge into clinical applications through innovative diagnostic and therapeutic approaches. Additionally, Nature Cancer welcomes clinical studies that inform cancer diagnosis, treatment, and prevention, along with contributions exploring the societal impact of cancer on a global scale. In addition to publishing original research, Nature Cancer will feature Comments, Reviews, News & Views, Features, and Correspondence that hold significant value for the diverse field of cancer research.