Clonal gene signatures predict prognosis in mesothelioma and lung adenocarcinoma

Yupei Lin ^1,2,3, Bryan M Burt ⁴, Hyun-Sung Lee ^3,5

¹Department of Medicine, Baylor College of Medicine, Houston, TX, 77030, USA.
²Institute for Clinical and Translational Research, Baylor College of Medicine, Houston, TX, 77030, USA.
³The Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, USA.
⁴Systems Onco-Immunology Laboratory, David J. Sugarbaker Division of Thoracic Surgery, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX, 77030, USA. BBurt@mednet.ucla.edu.
⁵Systems Onco-Immunology Laboratory, David J. Sugarbaker Division of Thoracic Surgery, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX, 77030, USA.
⁶Mesothelioma Treatment Center, Baylor St. Luke's Medical Center, Houston, TX, 77030, USA.
⁷Department of Medicine, Baylor College of Medicine, Houston, TX, 77030, USA. Chris.Amos@bcm.edu.
⁸Institute for Clinical and Translational Research, Baylor College of Medicine, Houston, TX, 77030, USA. Chris.Amos@bcm.edu.
⁹The Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, USA. Chris.Amos@bcm.edu.
¹⁰Department of Medicine, Baylor College of Medicine, Houston, TX, 77030, USA. chao.cheng@bcm.edu.
¹¹Institute for Clinical and Translational Research, Baylor College of Medicine, Houston, TX, 77030, USA. chao.cheng@bcm.edu.
¹²The Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, USA. chao.cheng@bcm.edu.

⁰Department of Medicine, Baylor College of Medicine, Houston, TX, 77030, USA.

Npj Precision Oncology +

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February 24, 2024

View abstract on PubMed

Summary

Researchers identified a new gene signature, PRACME, from multi-regional data to predict prognosis in malignant pleural mesothelioma (MPM). This signature offers valuable prognostic stratification for MPM patients, even showing cross-prediction with lung adenocarcinoma signatures.

Area Of Science

Oncology
Genomics
Transcriptomics

Background

Malignant pleural mesothelioma (MPM) is a rare, lethal cancer characterized by high intratumor heterogeneity (ITH).
Previous research developed a clonal gene signature (ORACLE) for lung adenocarcinoma, but its applicability in other heterogeneous cancers like MPM remained untested.

Purpose Of The Study

To identify prognostic biomarkers from multi-regional data for stratifying MPM patients.
To develop and validate a novel clonal gene signature for MPM.

Main Methods

Generated a multiregional RNA-seq dataset from 26 MPM patients (78 samples).
Integrated patient data with The Cancer Genome Atlas (TCGA) MPM data.
Selected 29 prognostic genes (PRACME) with high inter-tumor variability and low ITH; validated in independent datasets.

Main Results

The PRACME signature demonstrated significant prognostic value in MPM, with high scores correlating with poor prognosis.
PRACME and the ORACLE signature showed cross-predictive ability between MPM and lung adenocarcinoma.
Genomic similarities in copy number variation regions may explain the cross-prediction phenomenon.

Conclusions

The PRACME clonal gene signature provides effective prognostic stratification for malignant pleural mesothelioma patients.
This study highlights the importance of multi-regional transcriptomic data for developing prognostic biomarkers based on clonal genes.