Autophagy-Related Gene CXCR4 is a Potential Predictor of Prognosis and Immunotherapy Response for Gastric Cancer

Discov Med. 2023 Dec;35(179):1190-1201. doi: 10.24976/Discov.Med.202335179.115.

Abstract

Background: Autophagy is involved in the survival, differentiation, and activation of immune cell subsets. In this study, we determined the prognostic value and biological functions of autophagy genes in gastric cancer (GC).

Methods: The RNA sequencing dataset for gastric cancer was obtained. Differences in prognosis and enrichment pathways in non-negative matrix factorization (NMF) subclasses were analyzed. Next, we analyzed CXC chemokine receptor 4 (CXCR4) by differential expression, clinical value, immune effects, tumor mutation burden (TMB) values, somatic variants, and biological functions.

Results: NMF identified three subclasses. Among the three subclasses, there were differences in prognosis, immune cell infiltration, immune checkpoint genes, and enrichment pathways. Moreover, CXCR4 level was elevated in most tumors, and high CXCR4 level was related to poor prognosis in GC patients. CXCR4 expression was significantly correlated with B cells, eosinophils, macrophages, and plasma cells. In in vitro experiment, CXCR4 promoted GC cell proliferation.

Conclusions: Our results showed that CXCR4 is a promising biomarker for predicting prognosis and response to immunotherapy in GC.

Keywords: CXCR4; autophagy; bioinformatics; gastric cancer; immune infiltration.

MeSH terms

  • Autophagy / genetics
  • Humans
  • Immunotherapy
  • Prognosis
  • Receptors, CXCR4 / genetics
  • Stomach Neoplasms* / genetics
  • Stomach Neoplasms* / therapy

Substances

  • Receptors, CXCR4
  • CXCR4 protein, human