Abstract
Background: Metastatic melanoma has poor therapeutic response and may present resistance to chemotherapy or immunotherapy. Significant differences are observed in the survival time of patients with metastatic melanoma based on the administration of chemotherapy or immunotherapy; thus, we have explored the important role of specific differential genes between the two therapies in their effect on treatment response in melanoma.Methods: Metastatic melanoma gene expression data (RNAseq, mutation and methylation) and patient clinical information were downloaded from The Cancer Genome Atlas database and grouped according to chemotherapy or immunotherapy. The differentially expressed genes of the two groups were further screened for signature genes through a protein–protein interaction network and Lasso-Cox regression model. Then, differences in the treatment response, overall survival, mutation and methylation of characteristic genes were compared. Finally, western blot and real-time qPCR technology were used to detect the expression differences of the signature genes in metastatic melanoma tumor tissues in patients undergoing chemotherapy and immunotherapy.Results: The overall survival of the chemotherapy-based treatment group was significantly higher than that of the immunotherapy-based group. The immune infiltration level of immature dendritic cells (DCs) in the chemotherapy group was significantly higher than that in the immunotherapy group. Finally, seven signature genes were selected: CCKBR, KCNJ11, NMU, MMP13, ITGA10, IGFBP1 and CEACAM5. The results of these signature genes were significantly differentiated between the chemotherapy and immunotherapy groups in terms of overall survival and disease progression in response to treatment. In addition, differences in the expression of these genes were verified by western blot and real-time qPCR.Conclusion: In this study, significant differences in the expression of signature genes were verified. The findings indicate that immature DCs with potential application value should be considered and high mutation sites of signature genes should be identified to reduce the occurrence of treatment resistance.
Highlights
Malignant metastatic melanoma accounts for less than 5% of skin tumors, it causes the highest number of skin cancer-related deaths [1]
According to the screening rules, the gene expression data of patients with metastatic melanoma treated with chemotherapy and patients with immunotherapy were used in this study
The results showed that there was a significant difference in the response rate between the chemotherapy and immunotherapy patients
Summary
Malignant metastatic melanoma accounts for less than 5% of skin tumors, it causes the highest number of skin cancer-related deaths [1]. Significant differences are observed in the survival time of patients with metastatic melanoma based on the administration of chemotherapy or immunotherapy; we have explored the important role of specific differential genes between the two therapies in their effect on treatment response in melanoma. Western blot and real-time qPCR technology were used to detect the expression differences of the signature genes in metastatic melanoma tumor tissues in patients undergoing chemotherapy and immunotherapy. Seven signature genes were selected: CCKBR, KCNJ11, NMU, MMP13, ITGA10, IGFBP1 and CEACAM5 The results of these signature genes were significantly differentiated between the chemotherapy and immunotherapy groups in terms of overall survival and disease progression in response to treatment. The findings indicate that immature DCs with potential application value should be considered and high mutation sites of signature genes should be identified to reduce the occurrence of treatment resistance
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