Function of CD8+, conventional CD4+, and regulatory CD4+ T cell identification in lung cancer

Comput Biol Med. 2023 Jun:160:106933. doi: 10.1016/j.compbiomed.2023.106933. Epub 2023 Apr 28.

Abstract

Lung cancer is the malignant tumor with the highest mortality rate in the world. There is obvious heterogeneity within the tumor. Single cell sequencing technology enables scholars to obtain information about the cell type, status, subpopulation distribution and communication behavior between cells in the tumor microenvironment from the cellular level. However, due to the problem of sequencing depth, some genes with low expression cannot be detected, which results in that most of the specific genes of immune cells cannot be recognized, and lead to defects in the functional identification of immune cells. In this paper, we used single cell sequencing data of 12346 T cells in 14 treatment-naïve non-small-cell lung cancer patients to identify immune cell-specific genes and infer the function of three types of T cells. The method, named GRAPH-LC, implemented this function by gene interaction network and graph learning methods. Graph learning methods are used to extract genes feature and dense neural network is used to identify immune cell-specific genes. The experiments on 10-cross validation shows that the AUROC and AUPR reached at least 0.802, 0.815 on identifying cell-specific genes of three types of T cells. And we did functional enrichment analysis on the top 15 expressed genes. By functional enrichment analysis, we got 95 GO terms and 39 KEGG pathways that related to three types of T cells. The use of this technology will help to deeply understand the mechanism of the occurrence and development of lung cancer, find new diagnostic markers and therapeutic targets, and provide a theoretical reference for the precise treatment of lung cancer patients in the future.

Keywords: Gene interaction network; Graph learning methods; Immune cells; T cell.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • CD4-Positive T-Lymphocytes / pathology
  • CD8-Positive T-Lymphocytes / pathology
  • Carcinoma, Non-Small-Cell Lung* / genetics
  • Humans
  • Lung Neoplasms* / genetics
  • Lung Neoplasms* / pathology
  • T-Lymphocytes / pathology
  • Tumor Microenvironment