J Cancer 2021; 12(21):6588-6599. doi:10.7150/jca.63236

Research Paper

CD161, a promising Immune Checkpoint, correlates with Patient Prognosis: A Pan-cancer Analysis

Wenrui Ye1*, Cong Luo2*, Chenglong Li1, Zhixiong Liu1, Fangkun Liu1,3✉

1. Department of Neurosurgery, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan, 410008, China.
2. Department of Urology, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan, 410008, China.
3. National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan, 410008, China.
*These authors have contributed equally to this work and share first authorship.

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Citation:
Ye W, Luo C, Li C, Liu Z, Liu F. CD161, a promising Immune Checkpoint, correlates with Patient Prognosis: A Pan-cancer Analysis. J Cancer 2021; 12(21):6588-6599. doi:10.7150/jca.63236. Available from https://www.jcancer.org/v12p6588.htm

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Abstract

Background: CD161 is a promising immune checkpoint mainly expressed on natural killer (NK) cells and is essential for immunoregulatory functions. However, it remains obscure how CD161 correlates with immune infiltration and patient prognosis in pan-cancer.

Methods: We employed HPA, TCGA, GTEx, TIMER2.0, and GEPIA2 databases as well as R language to analyze and visualize CD161 in cancers. Our twenty-four glioma samples were sequenced for validation.

Results: Overall, CD161 was differentially expressed between most paired cancer and normal controls. Higher CD161 expression was associated with poorer overall survival (OS) in the TCGA LGG (HR = 2.18, 95%CI = 1.79-2.66, P < 0.001) and UVM (HR = 1.32, 95%CI = 1.05-1.65, P = 0.016) cohorts. In these two cancer types, CD161 was significantly correlated with expression levels of recognized immune checkpoints and the abundance of markers of specific immune subsets, including CD8+ T cells, dendric cells (DCs), M2 macrophages, and exhausted T cells (Texs). In addition, CD161 was involved in several immune pathways in LGG and UVM, highlighting its role in regulating immune processes in the context of oncology.

Conclusions: CD161 is a potential prognostic biomarker and immunotherapy target in human cancers, especially brain lower grade gliomas.

Keywords: CD161, biomarker, cancer, bioinformatics, prognosis, immune infiltration