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Research Article
Dong Li
Qilu Hospital of Shandong University
Corresponding Author
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Background: Melanoma is a serious form of skin cancer that begins in melanocytes. Metastasis, somatic mutations and gene expression profiles are important prognostic factors for melanoma patients. However, accurate prediction of patient prognosis remains an unsolved problem for the disease. This study was to develop a novel gene profile to accurately classify melanoma patients into subgroups with different survival probabilities.
Methods: Survival-related genes were determined by Kaplan–Meier survival analysis and multivariate analysis using the expression and clinical data of 467 melanoma patients from The Cancer Genome Atlas (TCGA) database and validated in an independent Gene Expression Omnibus (GEO) dataset. Feature selection was performed by the Least Absolute Shrinkage and Selection Operator (LASSO) method. A prognostic 23-gene score was established and compared with two known gene-expression risk scores. The stratification of melanoma patients was performed by unsupervised hierarchical clustering of 23 gene expression levels to identify clusters of melanoma patients with different survival probabilities.
Results: The LASSO model comprising 23 genes was considered as the optimal model. The 23-gene score was associated with increased mortality in melanoma patients regardless of clinicopathological characteristics. Hierarchical clustering analysis of the 23 genes revealed three subgroups of melanoma patients. The cluster3 melanoma tumours were associated with higher 23-gene score and poorer overall survival than cluster1 and cluster2 tumours. The 23-gene score had higher area under curve (0.76) than the 8-gene risk score and IRGs score (0.58 and 0.59) in the prediction of overall survival of melanoma patients.
Conclusions: The 23-gene score is superior to the two established prognostic gene signatures in the prediction of prognosis of melanoma patients.
Keywords
melanoma, the 23-gene signature, overall survival
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This is a list of supplementary files associated with this preprint. Click to download.
- Tables.pdf
- STables.docx
- SupplementaryFigure1.tiff
Supplementary Figure1. GSEA based on the expression of GEO dataset revealed significant pathways in the low 23-gene score group, including glycosaminoglycan degradation (A) and RNA polymerase (B).
- supplementaryFigure2.tif
Supplementary Figure2. Kaplan–Meier survival analysis of OS with the 23-gene score in subgroups of melanoma patients stratified by age, gender and prior malignancy in the TCGA cohort (A-F).
- supplementaryFigure3.tif
Supplementary Figure3. Kaplan–Meier survival analysis of OS with the 23-gene score in subgroups of melanoma patients stratified by cancer stage, BRAF mutation and NRAS mutation in the TCGA cohort (A-F).
- supplementaryFigure4.tif
Supplementary Figure4. Kaplan–Meier survival analysis of OS with the 23-gene score in subgroups of melanoma patients stratified by age and gender in the GEO cohort (A-D).
- supplementaryFigure5.tif
Supplementary Figure5. Kaplan–Meier survival analysis of OS with the 23-gene score in subgroups of melanoma patients stratified by distant metastasis, BRAF mutation and NRAS mutation in the GEO cohort (A-F).
- supplementaryFigure6.tiff
Supplementary Figure6. The ROC curves of the 23-gene score, 8-gene score and IRGs score in the TCGA dataset.
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This preprint is under consideration at World Journal of Surgical Oncology. A preprint is a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research Article
Dong Li
Qilu Hospital of Shandong University
Corresponding Author
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Under Review
Version 1
Posted 03 Mar, 2021
No community comments so far
Reviewers invited
Invitations sent on 28 Feb, 2021
Editor assigned
On 24 Feb, 2021
Submission checks complete
On 24 Feb, 2021
Editor invited
On 24 Feb, 2021
First submitted
On 21 Feb, 2021
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background: Melanoma is a serious form of skin cancer that begins in melanocytes. Metastasis, somatic mutations and gene expression profiles are important prognostic factors for melanoma patients. However, accurate prediction of patient prognosis remains an unsolved problem for the disease. This study was to develop a novel gene profile to accurately classify melanoma patients into subgroups with different survival probabilities.
Methods: Survival-related genes were determined by Kaplan–Meier survival analysis and multivariate analysis using the expression and clinical data of 467 melanoma patients from The Cancer Genome Atlas (TCGA) database and validated in an independent Gene Expression Omnibus (GEO) dataset. Feature selection was performed by the Least Absolute Shrinkage and Selection Operator (LASSO) method. A prognostic 23-gene score was established and compared with two known gene-expression risk scores. The stratification of melanoma patients was performed by unsupervised hierarchical clustering of 23 gene expression levels to identify clusters of melanoma patients with different survival probabilities.
Results: The LASSO model comprising 23 genes was considered as the optimal model. The 23-gene score was associated with increased mortality in melanoma patients regardless of clinicopathological characteristics. Hierarchical clustering analysis of the 23 genes revealed three subgroups of melanoma patients. The cluster3 melanoma tumours were associated with higher 23-gene score and poorer overall survival than cluster1 and cluster2 tumours. The 23-gene score had higher area under curve (0.76) than the 8-gene risk score and IRGs score (0.58 and 0.59) in the prediction of overall survival of melanoma patients.
Conclusions: The 23-gene score is superior to the two established prognostic gene signatures in the prediction of prognosis of melanoma patients.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
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