Dataset Information

Novel oxidative stress-related prognostic biomarkers for melanoma associated with tumor metastasis.

ABSTRACT:

Abstract

Skin cutaneous melanoma (SKCM) is a prevalent skin cancer whose metastatic form is dangerous due to its high morbidity and mortality. Previous studies have systematically established the vital role of oxidative stress (OS) in melanoma progression. This study aimed to identify prognostic OS genes closely associated with SKCM and illustrate their potential mechanisms. Transcriptome data and corresponding clinical traits of patients with SKCM were retrieved from The Cancer Genome Atlas and Gene Expression Omnibus databases. A weighted gene co-expression network analysis was conducted to identify relationships between clinical features and OS genes in specific modules. Subsequently, Cox regression analysis was performed on candidate OS genes; four hub prognosis-associated OS genes (AKAP9, VPS13C, ACSL4, and HMOX2) were identified to construct a prognostic model. After a series of bioinformatics analysis, our prognostic model was identified significantly associated with the overall survival of patients with SKCM and metastatic ability of the cancer. Furthermore, our risk model demonstrated improved diagnostic accuracy in the Cancer Genome Atlas and Gene Expression Omnibus cohorts. In addition, we established 2 nomograms based on either risk score or hub genes, which displayed favorable discriminating ability for SKCM. Our results provide novel insight into the potential applications of OS-associated genes in SKCM.

SUBMITTER: Wu X

PROVIDER: S-EPMC7909214 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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Novel oxidative stress-related prognostic biomarkers for melanoma associated with tumor metastasis.

Wu Xianpei X Zhao Jinmin J

Medicine 20210201 8

<h4>Abstract</h4>Skin cutaneous melanoma (SKCM) is a prevalent skin cancer whose metastatic form is dangerous due to its high morbidity and mortality. Previous studies have systematically established the vital role of oxidative stress (OS) in melanoma progression. This study aimed to identify prognostic OS genes closely associated with SKCM and illustrate their potential mechanisms. Transcriptome data and corresponding clinical traits of patients with SKCM were retrieved from The Cancer Genome A ...[more]

PMID: 33663112

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Project description:Circulating tumor cells (CTCs) are critical in the development of distant organ tumor metastasis, and are associated with advanced cancer stage and poor patient outcome. Here, we present the first genome-wide nucleotide-level characterization of CTCs. Our single-nucleotide polymorphism (SNP) analysis in patients with melanoma involved: 1) global comparative genomic analysis of CTCs and matched regional metastases, 2) identification of key genomic aberrations in CTCs, 3) verification of these target genes in aggressive distant tumor metastases, and 4) evidence of selective expression and functional consequence of CTC-associated genes in melanomas. We report 131 aberrant loci in CTCs that are potentially pro-metastatic, and show that such expression of a 5-marker gene panel (CSMD2, CNTNAP5, FLJ14051, ADAM6, TRPM2) in melanomas confers prognostic utility. Successful treatment of melanoma requires understanding of the metastatic process and identification of patients with tumors most likely to develop aggressive metastatic disease. Melanomas are heterogeneous, and CTCs have long been recognized as vehicles for cancer spread, representing particularly aggressive tumor clones that can evolve into successful clinical metastases. Elucidation of genomic aberrations in CTCs will aid in the development of prognostic biomarkers and therapeutic strategies to target CTCs to prevent or control distant cancer spread. This study provides the first detailed genomic confirmation of the close relation between CTCs and tumor metastases, and illustrates how CTCs can be utilized as a novel approach and rational source for identification of pro-metastatic genes in cancer research. Three individual patient cohorts were utilized in the study. CNV and LOH loci were evaluated initially in metastatic melanoma patients (n=13) in a discovery cohort. SNP loci that harbored CNV/LOH in CTCs were then separately verified for: (a) presence in distant organ metastasis (AJCC Stage IV melanoma) (n=27), and (b) relevance to prognosis in regional melanoma metastasis (AJCC Stage III melanoma) (n=35). The first discovery patient cohort group was utilized for capture of CTCs, and consisted of peripheral blood mononuclear cell (PBMC) and tumor specimens from metastatic melanoma patients (n=13). CTC-related loci were verified in a second cohort of patients with Stage IV distant organ metastases (n=27), including 15 brain, 4 lung, and 8 gastrointestinal (bowel, liver) metastases. The third patient cohort consisted of early passage (<12) established melanoma cell lines derived from 35 regional melanoma metastases (Stage III) for evaluation of the prognostic utility of the CTC-associated aberrant loci.

Dataset Information

Novel oxidative stress-related prognostic biomarkers for melanoma associated with tumor metastasis.

Abstract

Publications

Novel oxidative stress-related prognostic biomarkers for melanoma associated with tumor metastasis.

Similar Datasets

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