Shared Gene Expression and Immune Pathway Changes Associated with Progression from Nevi to Melanoma.
Shared Gene Expression and Immune Pathway Changes Associated with Progression from Nevi to Melanoma.
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DOI：
10.3390/cancers14010003
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发表时间：
2021-12-21
期刊：
影响因子：
5.2
通讯作者：
Hastings KT
中科院分区：
文献类型：
--
作者：
Borden ES;Adams AC;Buetow KH;Wilson MA;Bauman JE;Curiel-Lewandrowski C;Chow HS;LaFleur BJ;Hastings KT
黑色素瘤是一种致命的皮肤癌，黑色素瘤的发病率正在上升。化学预防，使用小分子药物来防止癌症的发展，是一项关键的战略，可以减轻黑色素瘤对社会的负担。我们研究的长期目标是开发一种从痣到黑色素瘤进展的基因标志物。我们发现，少数基因可以区分痣和黑色素瘤，并在独立的数据集上识别与从痣进展到黑色素瘤相关的共享基因和免疫相关途径。这项研究证明了(1)通过使用基因签名作为替代终点来辅助黑色素瘤化学预防试验的新方法，以及(2)确定黑色素瘤进展的基因签名生物标记物的可行性。有必要确定黑色素瘤进展的分子生物标记物，以帮助开发降低黑色素瘤发病率的化学预防策略。使用包含发育不良痣和黑色素瘤或黑色素瘤的基因表达的数据集，我们进行差异基因表达分析和正则化回归模型，以确定与从痣进展到黑色素瘤相关的基因和途径。少数基因区分了色素痣和黑色素瘤。在三个独立的数据集中，七个基因在色素痣和黑色素瘤之间的差异表达被鉴定出来。C1QB、CXCL9、CXCL10、DFNA5(GSDME)、FCGR1B和PRAME在黑色素瘤中增加，SCGB1D2在黑色素瘤中减少，与发展为黑色素瘤的发育不良痣或痣相比。进一步支持与黑色素瘤发生有关，这些基因的表达呈线性变化，从良性痣到发育不良痣到放射状生长期黑色素瘤再到垂直生长期黑色素瘤。与黑色素瘤进展相关的基因显示，与免疫系统相关的多条途径显著丰富。这项研究展示了(1)生物信息学方法在黑色素瘤化学预防临床试验中的新应用，以及(2)确定黑色素瘤发生的基因标志性生物标记物的可行性。
Melanoma is a deadly skin cancer, and the incidence of melanoma is rising. Chemoprevention, using small molecule drugs to prevent the development of cancer, is a key strategy that could reduce the burden of melanoma on society. The long-term goal of our study is to develop a gene signature biomarker of progression from nevi to melanoma. We found that a small number of genes can distinguish nevi from melanoma and identified shared genes and immune-related pathways that are associated with progression from nevi to melanoma across independent datasets. This study demonstrates (1) a novel approach to aid melanoma chemoprevention trials by using a gene signature as a surrogate endpoint and (2) the feasibility of determining a gene signature biomarker of melanoma progression. There is a need to identify molecular biomarkers of melanoma progression to assist the development of chemoprevention strategies to lower melanoma incidence. Using datasets containing gene expression for dysplastic nevi and melanoma or melanoma arising in a nevus, we performed differential gene expression analysis and regularized regression models to identify genes and pathways that were associated with progression from nevi to melanoma. A small number of genes distinguished nevi from melanoma. Differential expression of seven genes was identified between nevi and melanoma in three independent datasets. C1QB, CXCL9, CXCL10, DFNA5 (GSDME), FCGR1B, and PRAME were increased in melanoma, and SCGB1D2 was decreased in melanoma, compared to dysplastic nevi or nevi that progressed to melanoma. Further supporting an association with melanomagenesis, these genes demonstrated a linear change in expression from benign nevi to dysplastic nevi to radial growth phase melanoma to vertical growth phase melanoma. The genes associated with melanoma progression showed significant enrichment of multiple pathways related to the immune system. This study demonstrates (1) a novel application of bioinformatic approaches to aid clinical trials of melanoma chemoprevention and (2) the feasibility of determining a gene signature biomarker of melanomagenesis.
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DOI：
10.1084/jem.20200962
发表时间：
2021-09-06
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Fukuda K;Okamura K;Riding RL;Fan X;Afshari K;Haddadi NS;McCauley SM;Guney MH;Luban J;Funakoshi T;Yaguchi T;Kawakami Y;Khvorova A;Fitzgerald KA;Harris JE
通讯作者：
Harris JE
DOI：
10.1002/prca.201300105
发表时间：
2014-06
期刊：
Proteomics. Clinical applications
影响因子：
--
作者：
Aggarwal N;Sloane BF
通讯作者：
Sloane BF
影响因子：
78.5
作者：
Bresnick, Anne R.;Weber, David J.;Zimmer, Danna B.
通讯作者：
Zimmer, Danna B.
影响因子：
2.3
作者：
Clarke, Loren E.;Mabey, Brent;Elder, David E.
通讯作者：
Elder, David E.
影响因子：
3.7
作者：
Chan HS;Chang SJ;Wang TY;Ko HJ;Lin YC;Lin KT;Chang KM;Chuang YJ
通讯作者：
Chuang YJ