Correlation of CCL8 expression with immune cell infiltration of skin cutaneous melanoma: potential as a prognostic indicator and therapeutic pathway

Abstract Background The tumor microenvironment (TME) is critical in the progression and metastasis of skin cutaneous melanoma (SKCM). Differences in tumor-infiltrating immune cells (TICs) and their gene expression have been linked to cancer prognosis. Given that immunotherapy can be effective agains...

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Autores principales:	Peipei Yang, Wanrong Chen, Hua Xu, Junhan Yang, Jinghang Jiang, Yunhui Jiang, Ganglin Xu
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	Tumor microenvironment Tumor-infiltrating immune cells Skin cutaneous melanoma M1 macrophages Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Cytology QH573-671
Acceso en línea:	https://doaj.org/article/ff4a16d5254e4138b8cba66de816fe8a
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spelling	oai:doaj.org-article:ff4a16d5254e4138b8cba66de816fe8a2021-12-05T12:23:38ZCorrelation of CCL8 expression with immune cell infiltration of skin cutaneous melanoma: potential as a prognostic indicator and therapeutic pathway10.1186/s12935-021-02350-81475-2867https://doaj.org/article/ff4a16d5254e4138b8cba66de816fe8a2021-11-01T00:00:00Zhttps://doi.org/10.1186/s12935-021-02350-8https://doaj.org/toc/1475-2867Abstract Background The tumor microenvironment (TME) is critical in the progression and metastasis of skin cutaneous melanoma (SKCM). Differences in tumor-infiltrating immune cells (TICs) and their gene expression have been linked to cancer prognosis. Given that immunotherapy can be effective against SKCM, we aimed to identify key genes that regulate the immunological state of the TME in SKCM. Methods Data from 471 SKCM patients in the The Cancer Genome Atlas were analyzed using ESTIMATE algorithms to generate an ImmuneScore, StromalScore, and EstimateScore for each patient. Patients were classified into low- or high-score groups based on median values, then compared in order to identify differentially expressed genes (DEGs). Then a protein–protein interaction (PPI) network was developed, and a prognostic model was created using uni- and multivariate Cox regression as well as the least absolute shrinkage and selection operator (LASSO). Key DEGs were identified using the web-based tool GEPIA. Profiles of TIC subpopulations in each patient were analyzed using CIBORSORT, and possible correlations between key DEG expression and TICs were explored. Levels of CCL8 were determined in SKCM and normal skin tissue using immunohistochemistry. Results Two scores correlated positively with the prognosis of SKCM patients. Comparison of the low- and high-score groups revealed 1684 up-regulated and 18 down-regulated DEGs, all of which were enriched in immune-related functions. The prognostic model identified CCL8 as a key gene, which CIBERSORT found to correlate with M1 macrophages. Immunohistochemistry revealed strong expression in SKCM tissue, but failed to detect the protein in normal skin tissue. Conclusions CCL8 is a potential prognostic marker for SKCM, and it may become an effective target for melanoma in which M1 macrophages play an important role.Peipei YangWanrong ChenHua XuJunhan YangJinghang JiangYunhui JiangGanglin XuBMCarticleTumor microenvironmentTumor-infiltrating immune cellsSkin cutaneous melanomaM1 macrophagesNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282CytologyQH573-671ENCancer Cell International, Vol 21, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Tumor microenvironment Tumor-infiltrating immune cells Skin cutaneous melanoma M1 macrophages Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Cytology QH573-671
spellingShingle	Tumor microenvironment Tumor-infiltrating immune cells Skin cutaneous melanoma M1 macrophages Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Cytology QH573-671 Peipei Yang Wanrong Chen Hua Xu Junhan Yang Jinghang Jiang Yunhui Jiang Ganglin Xu Correlation of CCL8 expression with immune cell infiltration of skin cutaneous melanoma: potential as a prognostic indicator and therapeutic pathway
description	Abstract Background The tumor microenvironment (TME) is critical in the progression and metastasis of skin cutaneous melanoma (SKCM). Differences in tumor-infiltrating immune cells (TICs) and their gene expression have been linked to cancer prognosis. Given that immunotherapy can be effective against SKCM, we aimed to identify key genes that regulate the immunological state of the TME in SKCM. Methods Data from 471 SKCM patients in the The Cancer Genome Atlas were analyzed using ESTIMATE algorithms to generate an ImmuneScore, StromalScore, and EstimateScore for each patient. Patients were classified into low- or high-score groups based on median values, then compared in order to identify differentially expressed genes (DEGs). Then a protein–protein interaction (PPI) network was developed, and a prognostic model was created using uni- and multivariate Cox regression as well as the least absolute shrinkage and selection operator (LASSO). Key DEGs were identified using the web-based tool GEPIA. Profiles of TIC subpopulations in each patient were analyzed using CIBORSORT, and possible correlations between key DEG expression and TICs were explored. Levels of CCL8 were determined in SKCM and normal skin tissue using immunohistochemistry. Results Two scores correlated positively with the prognosis of SKCM patients. Comparison of the low- and high-score groups revealed 1684 up-regulated and 18 down-regulated DEGs, all of which were enriched in immune-related functions. The prognostic model identified CCL8 as a key gene, which CIBERSORT found to correlate with M1 macrophages. Immunohistochemistry revealed strong expression in SKCM tissue, but failed to detect the protein in normal skin tissue. Conclusions CCL8 is a potential prognostic marker for SKCM, and it may become an effective target for melanoma in which M1 macrophages play an important role.
format	article
author	Peipei Yang Wanrong Chen Hua Xu Junhan Yang Jinghang Jiang Yunhui Jiang Ganglin Xu
author_facet	Peipei Yang Wanrong Chen Hua Xu Junhan Yang Jinghang Jiang Yunhui Jiang Ganglin Xu
author_sort	Peipei Yang
title	Correlation of CCL8 expression with immune cell infiltration of skin cutaneous melanoma: potential as a prognostic indicator and therapeutic pathway
title_short	Correlation of CCL8 expression with immune cell infiltration of skin cutaneous melanoma: potential as a prognostic indicator and therapeutic pathway
title_full	Correlation of CCL8 expression with immune cell infiltration of skin cutaneous melanoma: potential as a prognostic indicator and therapeutic pathway
title_fullStr	Correlation of CCL8 expression with immune cell infiltration of skin cutaneous melanoma: potential as a prognostic indicator and therapeutic pathway
title_full_unstemmed	Correlation of CCL8 expression with immune cell infiltration of skin cutaneous melanoma: potential as a prognostic indicator and therapeutic pathway
title_sort	correlation of ccl8 expression with immune cell infiltration of skin cutaneous melanoma: potential as a prognostic indicator and therapeutic pathway
publisher	BMC
publishDate	2021
url	https://doaj.org/article/ff4a16d5254e4138b8cba66de816fe8a
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Correlation of CCL8 expression with immune cell infiltration of skin cutaneous melanoma: potential as a prognostic indicator and therapeutic pathway

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