Can ORACLE Predict Survival and Chemotherapy Response in Lung Adenocarcinoma?

By: Vanessa A. Carter, BS
Posted: Tuesday, February 11, 2025

According to Charles Swanton, MBPhD, FRCP, of University College London (UCL) Cancer Institute, The Francis Crick Institute, and University College London Hospitals, and colleagues, single-site needle biopsies are used to identify the differences in history and treatment response of human tumors, but identifying cancer biomarkers is difficult because of the spatiogenomic heterogeneity within these neoplasms. In an attempt to solve this sampling bias phenomenon, these investigators assessed clonally expressed biomarker Outcome Risk Associated Clonal Lung Expression (ORACLE) in patients with lung adenocarcinoma. Their results were published in Nature Cancer.

The study authors focused on 450 tumor regions using whole-exome and RNA-sequencing data from 184 patients with lung adenocarcinoma who were enrolled in the TRACERx study (ClinicalTrials.gov identifier NCT01888601). ORACLE risk scores were calculated and used to classify tumor samples into low- or high-risk subgroups.

It was found that ORACLE demonstrated the potential to predict the survival of patients with stage I lung cancer as well as response to chemotherapy—information that wasn’t previously attainable in this patient population using clinical standards. Of note, high ORACLE risk scores correlated with tumor regions that were likely to metastasize as well as better response to chemotherapy; the ORACLE risk score was found to be significantly associated with overall survival (P = .004) and lung cancer–specific survival (P = .03). Overall, ORACLE compiles genetic evolutionary measures that make up prognostic information as a concise, 23-transcript assay, the authors noted.

“ORACLE can now predict survival rates in patients diagnosed at the earliest stage,” stated coauthor Dhruva Biswas, MD, PhD, of UCL Cancer Institute, in an institutional press release. “If [these findings are] validated in larger cohorts of patients with lung cancer, doctors could one day use ORACLE to help make informed treatment decisions, bringing lessons from cancer evolution into the clinic.”

Disclosure: For full disclosures of the study authors, visit nature.com.

Nature Cancer

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