Research Paper Volume 16, Issue 5 pp 4518—4540

Tumor-infiltrating macrophage associated lncRNA signature in cutaneous melanoma: implications for diagnosis, prognosis, and immunotherapy

Qi Wan1, *, , Yuhua Deng2, *, , Ran Wei1, , Ke Ma1, , Jing Tang1, , Ying-Ping Deng1, ,

  • 1 Department of Ophthalmology, West China Hospital of Sichuan University, Chengdu, Sichuan, China
  • 2 Department of Infection Control, West China Hospital of Sichuan University, Chengdu, Sichuan, China
* Equal contribution and co-first authors

Received: September 7, 2023       Accepted: January 8, 2024       Published: March 13, 2024      

https://doi.org/10.18632/aging.205606
How to Cite

Copyright: © 2024 Wan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Along with the increasing knowledge of long noncoding RNA, the interaction between the long noncoding RNA (lncRNA) and tumor immune infiltration is increasingly valued. However, there is a lack of understanding of correlation between regulation of specific lncRNAs and tumor-infiltrating macrophages within melanoma. In this research, a macrophage associated lncRNA signature was identified by multiple machine learning algorithms and the robust and effectiveness of signature also validated in other independent datasets. The signature contained six specific lncRNAs (PART1, LINC00968, LINC00954, LINC00944, LINC00518 and C20orf197) was constructed, which could diagnose melanoma and predict the prognosis of patients. Moreover, our signature achieves higher accuracy than the previous well-established markers and regarded as an independent prognostic indicator. The pathway enrichment revealed that these lncRNAs were closely correlated with many immune processes. In addition, the signature was associated with different immune microenvironment and applied to predict response of immune checkpoint inhibitor therapy (low risk of patients well respond to anti-PD-1 therapy and high risk is insensitive to anti-CTLA-4 therapy). Therefore, our finding supplies a more accuracy and effective lncRNA signature for tumor-infiltrating macrophages targeting treatment approaches and affords a new clinical application for predicting the response of immunotherapies in melanomas.

Abbreviations

lncRNA: long noncoding RNA; DEMlncRNAs: Differential expressed macrophage associated lncRNAs; TCGA: The Cancer Genome Atlas database; GEO: Gene Expression Omniniub; LASSO: Least Absolute Shrinkage and Selection Operator; SVM-RFE: Support Vector Machine-Recursive Feature Elimination; RF-VS: Random Forests Variable selection; OS: overall survival; AUC: The area under the curve; ROC: Receiver operating characteristic curves.