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Tumour gene expression signature in primary melanoma predicts long-term outcomes
- Source :
- Nature Communications, Nature Communications, Vol 12, Iss 1, Pp 1-14 (2021)
- Publication Year :
- 2021
- Publisher :
- Springer Science and Business Media LLC, 2021.
-
Abstract
- Funder: University of Sydney Medical Foundation<br />Funder: Department of Health | National Health and Medical Research Council (NHMRC); doi: https://doi.org/10.13039/501100000925<br />Adjuvant systemic therapies are now routinely used following resection of stage III melanoma, however accurate prognostic information is needed to better stratify patients. We use differential expression analyses of primary tumours from 204 RNA-sequenced melanomas within a large adjuvant trial, identifying a 121 metastasis-associated gene signature. This signature strongly associated with progression-free (HR = 1.63, p = 5.24 × 10−5) and overall survival (HR = 1.61, p = 1.67 × 10−4), was validated in 175 regional lymph nodes metastasis as well as two externally ascertained datasets. The machine learning classification models trained using the signature genes performed significantly better in predicting metastases than models trained with clinical covariates (pAUROC = 7.03 × 10−4), or published prognostic signatures (pAUROC < 0.05). The signature score negatively correlated with measures of immune cell infiltration (ρ = −0.75, p < 2.2 × 10−16), with a higher score representing reduced lymphocyte infiltration and a higher 5-year risk of death in stage II melanoma. Our expression signature identifies melanoma patients at higher risk of metastases and warrants further evaluation in adjuvant clinical trials.
- Subjects :
- 0301 basic medicine
Oncology
Time Factors
General Physics and Astronomy
631/67/1857
Metastasis
Tumour biomarkers
Machine Learning
0302 clinical medicine
Databases, Genetic
Cancer genomics
Melanoma
Multidisciplinary
article
Prognosis
Progression-Free Survival
Gene Expression Regulation, Neoplastic
Treatment Outcome
030220 oncology & carcinogenesis
38/39
141
medicine.medical_specialty
Science
38/90
631/67/69
631/67/1813/1634
General Biochemistry, Genetics and Molecular Biology
03 medical and health sciences
Internal medicine
medicine
Humans
Progression-free survival
Neoplasm Staging
Proportional Hazards Models
45/91
Proportional hazards model
business.industry
Gene Expression Profiling
Reproducibility of Results
Cancer
General Chemistry
Gene signature
medicine.disease
Clinical trial
Gene expression profiling
030104 developmental biology
Multivariate Analysis
business
Subjects
Details
- ISSN :
- 20411723
- Volume :
- 12
- Database :
- OpenAIRE
- Journal :
- Nature Communications
- Accession number :
- edsair.doi.dedup.....02f0192a8f24d7cd4bbe5f31f7d748e0