Evaluation of drug sensitivity, immunological characteristics, and prognosis in melanoma patients using an endoplasmic reticulum stress-associated signature based on bioinformatics and pan-cancer analysis

Hounye, Alphonse Houssou1; Hu, Bingqian2; Wang, Zheng3; Wang, Jiaoju1; Cao, Cong1; Zhang, Jianglin4; Hou, Muzhou1; Qi, Min5

2023-08-01

10.1007/s00109-023-02365

JOURNAL OF MOLECULAR MEDICINE-JMM   Impact Factor & Quartile

0946-2716

1432-1440

["We aimed to develop endoplasmic reticulum (ER) stress-related risk signature to predict the prognosis of melanoma and elucidate the immune characteristics and benefit of immunotherapy in ER-related risk score-defined subgroups of melanoma based on a machine learning algorithm. Based on The Cancer Genome Atlas (TCGA) melanoma dataset (n = 471) and GTEx database (n = 813), 365 differentially expressed ER-associated genes were selected using the univariate Cox model and LASSO penalty Cox model. Ten genes impacting OS were identified to construct an ER-related signature by using the multivariate Cox regression method and validated with the Gene Expression Omnibus (GEO) dataset. Thereafter, the immune features, CNV, methylation, drug sensitivity, and the clinical benefit of anticancer immune checkpoint inhibitor (ICI) therapy in risk score subgroups, were analyzed. We further validated the gene signature using pan-cancer analysis by comparing it to other tumor types. The ER-related risk score was constructed based on the ARNTL, AGO1, TXN, SORL1, CHD7, EGFR, KIT, HLA-DRB1 KCNA2, and EDNRB genes. The high ER stress-related risk score group patients had a poorer overall survival (OS) than the low-risk score group patients, consistent with the results in the GEO cohort. The combined results suggested that a high ER stress-related risk score was associated with cell adhesion, gamma phagocytosis, cation transport, cell surface cell adhesion, KRAS signalling, CD4 T cells, M1 macrophages, naive B cells, natural killer (NK) cells, and eosinophils and less benefitted from ICI therapy. Based on the expression patterns of ER stress-related genes, we created an appropriate predictive model, which can also help distinguish the immune characteristics, CNV, methylation, and the clinical benefit of ICI therapy.","Key messages","Melanoma is the cutaneous tumor with a high degree of malignancy, the highest fatality rate, and extremely poor prognosis.Model usefulness should be considered when using models that contained more features.We constructed the Endoplasmic Reticulum stress-associated signature using TCGA and GEO database based on machine learning algorithm.ER stress-associated signature has excellent ability for predicting prognosis for melanoma."]

Bioinformatic Tumor immune microenvironment Melanoma The Cancer Genome Atlas (TCGA) Dermatology

SCI

English

Others

Genetics & Heredity ; Research & Experimental Medicine

Genetics & Heredity ; Medicine, Research & Experimental

WOS:001061928000001

SPRINGER HEIDELBERG

CLINICAL MEDICINE

Web of Science

1.Cent South Univ, Sch Math & Stat, Changsha 410083, Peoples R China
2.Cent South Univ, Xiangya Hosp, Dept Dermatol, Changsha 410000, Peoples R China
3.Hunan First Normal Univ, Sch Comp Sci, Changsha 410205, Peoples R China
4.Southern Univ Sci & Technol, Shenzhen Peoples Hosp Jinan Univ, Affiliated Hosp 1, Clin Med Coll 2,Dept Dermatol, Shenzhen 518020, Guangdong, Peoples R China
5.Cent South Univ, Xiangya Hosp, Dept Plast Surg, Changsha 410008, Peoples R China

Hounye, Alphonse Houssou,Hu, Bingqian,Wang, Zheng,et al. Evaluation of drug sensitivity, immunological characteristics, and prognosis in melanoma patients using an endoplasmic reticulum stress-associated signature based on bioinformatics and pan-cancer analysis[J]. JOURNAL OF MOLECULAR MEDICINE-JMM,2023.

Hounye, Alphonse Houssou.,Hu, Bingqian.,Wang, Zheng.,Wang, Jiaoju.,Cao, Cong.,...&Qi, Min.(2023).Evaluation of drug sensitivity, immunological characteristics, and prognosis in melanoma patients using an endoplasmic reticulum stress-associated signature based on bioinformatics and pan-cancer analysis.JOURNAL OF MOLECULAR MEDICINE-JMM.

Hounye, Alphonse Houssou,et al."Evaluation of drug sensitivity, immunological characteristics, and prognosis in melanoma patients using an endoplasmic reticulum stress-associated signature based on bioinformatics and pan-cancer analysis".JOURNAL OF MOLECULAR MEDICINE-JMM (2023).