A combined aging and immune prognostic signature predict prognosis and responsiveness to immunotherapy in melanoma

Wenchang Lv; YuanYuan Zhan; Yufang Tan; Yiping Wu; Hongbo Chen

doi:10.3389/fphar.2022.943944

A combined aging and immune prognostic signature predict prognosis and responsiveness to immunotherapy in melanoma

Front Pharmacol. 2022 Aug 11:13:943944. doi: 10.3389/fphar.2022.943944. eCollection 2022.

Authors

Wenchang Lv¹, YuanYuan Zhan¹, Yufang Tan¹, Yiping Wu¹, Hongbo Chen¹

Affiliation

¹ Department of Plastic and Cosmetic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Abstract

Background: Melanoma is the most lethal, and one of the most aggressive forms of cutaneous malignancies, which poor response to treatment has always puzzled clinicians. As is known to all, aging and immune microenvironment are two crucial factors impacting melanoma biological progress through the tumor microenvironment (TME). However, reliable biomarkers for predicting melanoma prognosis based on aging and immune microenvironment and therapeutic efficacy of immune checkpoints remain to be determined. Methods: The aging-related genes (ARGs) were obtained from the Human Ageing Genomic Resources and immune-related genes (IRGs) were downloaded from the Immunology database as well as Analysis Portal (ImmPort) database. Next, we initially performed LASSO regression and multivariate Cox regression to identify prognostic ARGs and IRGs in the TCGA and GSE65904 datasets, and firstly constructed a novel comprehensive index of aging and immune (CIAI) signature. Finally, in vitro molecular biology experiments were performed to assess the regulatory role of CNTFR in melanoma cell lines proliferation and migration, macrophage recruitment, and M2 polarization. Results: This novel CIAI signature consisted of 7 genes, including FOXM1, TP63, ARNTL, KIR2DL4, CCL8, SEMA6A, and CNTFR, in which melanoma patients in the high-CIAI group had shorter OS, DSS, and PFI, indicating CIAI model served as an independent prognostic index. Moreover, we found the CIAI score was potentially correlated with immune scores, estimate score, immune cell infiltration level, tumor microenvironment, immunotherapy effect, and drug sensitivity. Finally, CNTFR might function as oncogenes in melanoma cell lines and the silencing of CNTFR reduced macrophage recruitment and M2 polarization. Conclusion: In this study, we have first presented a novel prognostic CIAI model applied to assess immune checkpoint therapy and the efficacy of conventional chemotherapy agents in melanoma patients. Thus providing a new insight for combating melanoma.

Keywords: aging; immune; immune checkpoint; melanoma; prognosis; tumor immune microenvironment.