Pan-cancer prognostic model and immune microenvironment analysis of natural killer cell-related genes

Caihong Li; Yuxin Huang; Xiaojuan Yi; Youpan Tang; Riki Okita; Jun He

doi:10.21037/tcr-24-434

Pan-cancer prognostic model and immune microenvironment analysis of natural killer cell-related genes

Transl Cancer Res. 2024 Apr 30;13(4):1936-1953. doi: 10.21037/tcr-24-434. Epub 2024 Apr 25.

Authors

Caihong Li^#¹, Yuxin Huang^#², Xiaojuan Yi², Youpan Tang³, Riki Okita⁴, Jun He⁵

Affiliations

¹ Department of Radiotherapy, The Second Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.
² Department of Clinical Medicine, Southwest Medical University, Luzhou, China.
³ Department of Gastroenterology, Zhongjiang People's Hospital, Deyang, China.
⁴ Department of Thoracic Surgery, National Hospital Organization Yamaguchi Ube Medical Center, Ube, Japan.
⁵ Department of Oncology, The Third Hospital of Mian Yang (Sichuan Mental Health Center), Mianyang, China.

^# Contributed equally.

Abstract

Background: Natural killer (NK) cells play a significant role in antitumor immunity and are closely related to tumor prognosis and recurrence. NK cell-based tumor immunotherapy, including immune checkpoint inhibition and CAR-engineered NK cells, is a promising area of research. However, there is a need for better NK cell-related models and associated biomarkers.

Methods: The sequences of NK cell-related genes were obtained from the published NK cell CRISPR/Cas9 library data, and the common genes were selected as NK cell-related genes. The RNA sequencing (RNA-seq) and clinical data of 32 solid tumors from The Cancer Genome Atlas (TCGA) were downloaded from the UCSC Xena database, and the RNA-seq data of normal samples were downloaded from the Genotype-Tissue Expression (GTEx) database. The differentially expressed NK cell-related genes (DENKGs) between the tumor and normal samples were analyzed. The DENKGs related to the prognosis of solid tumors were selected via univariate Cox analysis, and 32 kinds of solid tumor prognostic models were constructed using least absolute shrinkage and selection operator (LASSO) and multivariate Cox analysis. Survival, receiver operating characteristic (ROC), and independent prognostic analyses were employed to test the effectiveness of the model, along with a nomogram model and prediction curve. Differences in the immune pathways and microenvironment cells were analyzed between the high- and low-risk groups identified by the model.

Results: We constructed a pan-cancer prognostic model with 63 NK cell-related genes and further identified DEPDC1 and ASPM as potentially offering new directions in tumor research by literature screening.

Conclusions: In this study, 63 prognostic solid tumor markers were investigated using NK cell-related genes, and for the first time, a pan-cancer prognostic model was constructed to analyze their role in the immune microenvironment, which may contribute new insights into tumor research.

Keywords: ASPM; DEPDC1; Natural killer cell-related genes (NK cell-related genes); pan-cancer; prognosis.