Key candidate genes of STAT1 and CXCL10 in melanoma identified by integrated bioinformatical analysis

Huang, Lili; Chen, Jianhua; Zhao, Yu; Gu, Linaer; Shao, Xiaoyan; Li, Jiyu; Xu, Yu; Liu, Zhuqing; Xu, Qing

doi:10.1002/iub.2103

Cited by 8 publications

(6 citation statements)

References 35 publications

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“…39 In melanoma, CXCL10 was reported as a key candidate gene by integrated bioinformatics analysis. 40 The above research results indicated that the IRGs in our signature may be involved in the occurrence and development of SKCM.…”

Section: Discussionmentioning

confidence: 64%

<p>Development and Validation of an Immune-Related Gene Pair Signature in Skin Cutaneous Melanoma</p>

Xie¹,

Dong²,

Jiang³

et al. 2020

CCID

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Introduction Skin cutaneous melanoma (SKCM) is a common skin malignancy worldwide, and its metastasis and mortality rates are high. The molecular characteristics exhibited by tumor–immune interactions have drawn the attention from researchers. Therefore, increased knowledge and new strategies to identify effective immune-related biomarkers may improve the clinical management of SKCM by providing more accurate prognostic information. Patients and Methods In this study, we established a prognostic immune-related gene pair (IRGP) signature for predicting the survival of SKCM patients. The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases provided gene expression profiles together with clinical information, and the samples were randomly divided into three groups including the training, testing, and validation datasets. The regression model of least absolute shrinkage and selection operator (LASSO) helped to identify a 13-IRGP signature with a significant relation to the survival of SKCM patients. Results The training, TCGA, and independent sets have an average value of area under the curve of 0.79, 0.76, and 0.82, respectively. In addition, this 13-IRGP signature can noticeably divide SKCM patients into high-risk group and low-risk group with significantly different prognoses. Many biological activities such as gene family were enriched among the genes in our IRGP signature. While analyzing the risk signature and clinical characteristics, there was a large difference in the risk score between T stage and tumor stage grouping. Finally, we constructed a nomogram and forest plots of the risk score and clinical features. Conclusion In summary, we developed a robust 13-IRGP prognostic signature in SKCM, which can identify and provide new insights into immunological biomarkers.

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Section: Discussionmentioning

confidence: 64%

<p>Development and Validation of an Immune-Related Gene Pair Signature in Skin Cutaneous Melanoma</p>

Xie¹,

Dong²,

Jiang³

et al. 2020

CCID

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“…CXCL10, as a "key driver chemokine" as well as an effective target for treating autoimmune diseases [33], has been a target for novel cancer therapy in immune activation functions [34]. In melanoma, CXCL10 was reported as a key candidate gene by integrated bioinformatics analysis [35]. The above research results indicated that the IRGs in our signature may be involved in the occurrence and development of SKCM.…”

Section: Discussionmentioning

confidence: 69%

Development and Validation of An Immune-Related Gene Pair Signature in Skin Cutaneous Melanoma

Xie¹,

Dong²,

Jiang

et al. 2020

Preprint

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Skin cutaneous melanoma (SKCM) is a common skin malignancy worldwide, and its metastasis and mortality rates are high. The molecular characteristics exhibited by tumor-immune interactions have drawn the attention from researchers. Therefore, increased knowledge and new strategies to identify effective immune-related biomarkers may improve the clinical management of SKCM by providing more accurate prognostic information. In this study, we established a prognostic immune-related gene pair (IRGP) signature for predicting the survival of SKCM patients. The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases provided gene expression profiles together with clinical information, and the samples were randomly divided into three groups including the training, testing, and validation datasets. The regression model of least absolute shrinkage and selection operator (LASSO) helped to identify a 13-IRGP signature with a significant relation to the survival of SKCM patients. The training, TCGA, and independent sets have an average value of area under the curve of 0.79, 0.76, and 0.82, respectively. In addition, this 13-IRGP signature can noticeably divide SKCM patients into high-risk group and low-risk group with significantly different prognoses. Many biological activities such as gene family were enriched among the genes in our IRGP signature. While analyzing the risk signature and clinical characteristics, there was a large difference in the risk score between T stage and tumor stage grouping. Finally, we constructed a nomogram and forest plots of the risk score and clinical features. In summary, we developed a robust 13-IRGP prognostic signature in SKCM, which can identify and provide new insights into immunological biomarkers.

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“…Furthermore, STAT1 and CXCL10 affect bone destruction through the M1 polarization of macrophages [ 22 ]. CXCL10 and STAT1 have also been suggested as key candidate genes for understanding the molecular mechanism of melanoma [ 42 ]. STAT1 is known to be activated by IFN-γ.…”

Section: Discussionmentioning

confidence: 99%

Ionizing Radiation Selectively Increases CXC Ligand 10 Level via the DNA-Damage-Induced p38 MAPK-STAT1 Pathway in Murine J774A.1 Macrophages

Seo

Baik

Lee

et al. 2023

Cells

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Ionizing radiation (IR) is an important means of tumor treatment in addition to surgery and drugs. Attempts have been made to improve the efficiency of radiotherapy by identifying the various biological effects of IR on cells. Components of the tumor microenvironment, such as macrophages, fibroblasts, and vascular endothelial cells, influence cancer treatment outcomes through communication with tumor cells. In this study, we found that IR selectively increased the production of CXC motif chemokine ligand 10 (CXCL10), which is emerging as an important biomarker for determining the prognosis of anticancer treatments, without changing the levels of CXCL9 and CXCL11 in murine J774A.1 macrophages. Pretreatment with KU55933, an ataxia telangiectasia mutated (ATM) kinase inhibitor, significantly inhibited IR-induced CXCL10 production. In contrast, pretreatment with N-acetyl-cysteine or glutathione, a reactive oxygen species scavenger, did not inhibit IR-induced CXCL10 production. Further, we attempted to identify the intracellular molecular target associated with the IR-induced increase in CXCL10 secretion by J774A.1 macrophages. IR phosphorylated p38 mitogen-activated protein kinase (MAPK) and signal transducer and activator of transcription 1 (STAT1) in J774A.1 macrophages, and p38 MAPK and STAT1 were involved in CXCL10 via IR using pharmacological inhibitors (SB203580 and fludarabine, respectively) and the siRNA technique.

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Key candidate genes of STAT1 and CXCL10 in melanoma identified by integrated bioinformatical analysis

Cited by 8 publications

References 35 publications

<p>Development and Validation of an Immune-Related Gene Pair Signature in Skin Cutaneous Melanoma</p>

<p>Development and Validation of an Immune-Related Gene Pair Signature in Skin Cutaneous Melanoma</p>

Development and Validation of An Immune-Related Gene Pair Signature in Skin Cutaneous Melanoma

Ionizing Radiation Selectively Increases CXC Ligand 10 Level via the DNA-Damage-Induced p38 MAPK-STAT1 Pathway in Murine J774A.1 Macrophages

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