Research Paper Volume 13, Issue 19 pp 22912—22933
Significance of CD8+ T cell infiltration-related biomarkers and the corresponding prediction model for the prognosis of kidney renal clear cell carcinoma
- 1 Somatic Radiotherapy Department, Shandong Second Provincial General Hospital, Shandong Provincial ENT Hospital, Jinan 250023, Shandong, P.R. China
- 2 Head and Neck Radiotherapy Department, Shandong Provincial ENT Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250023, Shandong, P.R. China
- 3 Radiotherapy Oncology Department, The First Affiliated Hospital of Shandong First Medical University and Shandong Provincial Qianfoshan Hospital, Shandong Key Laboratory of Rheumatic Disease and Translational Medicine, Shandong Lung Cancer Institute, Jinan 250014, Shandong, P.R. China
- 4 Endocrinology Department, Shandong Provincial Qianfoshan Hospital, The First Hospital Affiliated with Shandong First Medical University, Jinan 250014, Shandong, P.R. China
- 5 Department of Oncology, Jinan Central Hospital, The First Hospital Affiliated with Shandong First Medical University, Jinan 250013, Shandong, P.R. China
- 6 Department of Radiotherapy Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan 250012, Shandong, P.R. China
- 7 Phase I Clinical Trial Center, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan 250012, Shandong, P.R. China
Received: May 26, 2021 Accepted: August 17, 2021 Published: October 4, 2021
https://doi.org/10.18632/aging.203584How to Cite
Copyright: © 2021 Tian 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.
Abstract
Cytotoxic T cells expressing cell surface CD8 played a key role in anti-cancer immunotherapy, including kidney renal clear cell carcinoma (KIRC). Here we set out to comprehensively analyze and evaluate the significance of CD8+ T cell-related markers for patients with KIRC. We checked immune cell response in KIRC and identified cell type-specific markers and related pathways in the tumor-infiltrating CD8+ T (TIL-CD8T) cells. We used these markers to explore their prognostic signatures in TIL-CD8+ T by evaluating their prognostic efficacy and group differences at various levels. Through pan-cancer analysis, 12 of 63 up-regulated and 162 of 396 down-regulated genes in CD8+ T cells were found to be significantly correlated with the survival prognosis. Based on our highly integrated multi-platform analyses across multiple datasets, we constructed a 6-gene risk scoring model specific to TIL-CD8T. In this model, high TIL-CD8 sig score was corresponding to a higher incidence frequency of copy number variation and drug sensitivity to sorafenib. Moreover, the prognosis of patients with the same or similar immune checkpoint gene levels could be distinguished from each other by TIL-CD8 sig score.
Abbreviations
TIL-CD8TSig: Tumor-Infiltrating CD8 T cell gene Signature; GDSC: Genomics of Drug Sensitivity in Cancer; CCLE: Cancer Cell Line Encyclopedia; GEO: Gene Expression Omnibus; TCGA: The Cancer Genome Atlas; LASSO: Least Absolute Shrinkage and Selection Operator; ssGSEA: Single-sample Gene Set Enrichment Analysis; NES: Normalized Enrichment Score; DCA: Decision Curve Analysis; GO: Gene Ontology; KEGG: Kyoto Encyclopedia of Genes and Genomes; TIDE: Tumour Immune Dysfunction and Exclusion; FPKM: Fragments Per Kilobase per Million; ICB: Immune Checkpoint Blockade; BP: Biological Process; MASS: Modern Applied Statistics with S; CNV: Copy Number Variation; AIC: Akaike Information Criterion.