Research Paper Volume 13, Issue 21 pp 24379—24401
Pyroptosis-related gene mediated modification patterns and immune cell infiltration landscapes in cutaneous melanoma to aid immunotherapy
- 1 Bone and Joint Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, People’s Republic of China
Received: August 2, 2021 Accepted: October 27, 2021 Published: November 9, 2021https://doi.org/10.18632/aging.203687
How to Cite
Copyright: © 2021 Meng et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Tumor occurrence, infiltration, and metastasis are significantly affected by the tumor microenvironment (TME). Increasing evidence has elucidated TME’s clinical significance in prognostic assessment and immunotherapy efficacy. Nonetheless, no studies have reported the potential pyroptosis-related genes (PRGs) function in TME immune cell infiltration. In this study, we systematically analyzed different PRG modification patterns in 685 cutaneous melanoma (CM) cases. We comprehensively explored the relationship between these PRG modification patterns and TME cell infiltration characteristics. Then, we used principal component analysis to construct a pyroptosis scoring system to quantify the PRG modification patterns in each CM patient. Three different PRG modification patterns were identified. Pyroptosis score was confirmed as an independent prognostic factor for CM patients. High pyroptosis score was characterized by high immunophenscore and more lymphocytes infiltration, such as T, B, and NK cells - indicating a strong ability to monitor and clear tumors, which may be responsible for the advantageous survival. Three independent cohorts that received immunotherapy confirmed the significant therapeutic efficacy and clinical benefit in high pyroptosis scores patients. This study revealed that the PRG modification patterns have a crucial effect on the CM complex and diverse microenvironment. Pyroptosis scores might serve as credible predictors of immunotherapy response and prognostic assessment. This provides a new direction for personalized immunotherapy strategies and appropriate immunotherapy candidates screening.
CM: cutaneous melanoma; PRG: pyroptosis-related gene; DEPRGs: differentially expressed PRGs; TME: tumor microenvironment; PCA: principal component analysis; CNV: copy number variation; ssGSEA: single sample gene set enrichment analysis; GSVA: gene set variation analysis; DEGs: differential expression genes; BP: biological process; CC: cellular component; MF: molecular function; FDR: false discovery rate; TMB: tumor mutation burden; KEGG: Kyoto Encyclopedia of Genes and Genomes; GO: Gene Ontology; GEO: Gene-Expression Omnibus; IPS: immunophenscore; ICB: Immune checkpoint blockade; IAR: Immune activation-related; RT: radiotherapy; IT: immunotherapy; PIR: peri-induction radiotherapy; PER: post-escape radiotherapy.