High expression of NXPH4 correlates with poor prognosis, metabolic reprogramming, and immune infiltration in colon adenocarcinoma

Zhe Sun; Haodi Wang; Yao Xu; Yichi Liu; Lu Wang; Ruijie Zhou; Runlong Zhou; Wenjian Ma; Tongcun Zhang

doi:10.21037/jgo-23-956

High expression of NXPH4 correlates with poor prognosis, metabolic reprogramming, and immune infiltration in colon adenocarcinoma

J Gastrointest Oncol. 2024 Apr 30;15(2):641-667. doi: 10.21037/jgo-23-956. Epub 2024 Apr 29.

Authors

Zhe Sun^#¹, Haodi Wang^#¹, Yao Xu^#², Yichi Liu¹, Lu Wang¹, Ruijie Zhou², Runlong Zhou², Wenjian Ma^{1

3}, Tongcun Zhang^{1

2}

Affiliations

¹ College of Biotechnology, Tianjin University of Science and Technology, Tianjin, China.
² Institute of Biology and Medicine, College of Life Sciences and Health, Wuhan University of Science and Technology, Wuhan, China.
³ Qilu Institute of Technology, Jinan, China.

^# Contributed equally.

Abstract

Background: Colon adenocarcinoma (COAD) is a prevalent gastrointestinal malignant disease with high mortality rate, and identification of novel prognostic biomarkers and therapeutic targets is urgently needed. Although neurexophilin 4 (NXPH4) has been investigated in several tumors, its role in COAD remains unclear. The aim of this study was to explore the prognostic value and potential functions of NXPH4 in COAD.

Methods: The expression of NXPH4 in COAD were analyzed using The Cancer Genome Atlas (TCGA) and datasets from the Gene Expression Omnibus (GEO) database. The prognostic value of NXPH4 was determined using Kaplan-Meier analysis and Cox regression analysis. To investigate the possible mechanism underlying the role of NXPH4 in COAD, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and gene set enrichment analysis (GSEA) were employed. The correlation between NXPH4 expression and immune cell infiltration levels was examined thorough single-sample gene set enrichment analysis (ssGSEA). Furthermore, the competing endogenous RNA (ceRNA) regulatory network that may be involved in NXPH4 in COAD was predicted and constructed through a variety of databases.

Results: NXPH4 expression was significantly higher in COAD tissue compared with normal colon tissues. Meanwhile, high expression of NXPH4 was associated with poor prognosis in COAD patients. GO-KEGG and GSEA analyses indicated that NXPH4 was associated with glycolysis and hypoxia pathway, and may promote COAD progression and metastasis by modulating metabolic reprogramming. ssGSEA analysis demonstrated that NXPH4 expression also associated with immune infiltration. Furthermore, we identified various microRNAs (miRNAs) and long noncoding RNAs (lncRNAs) as upstream regulators of NXPH4 in COAD.

Conclusions: The present study revealed that high expression of NXPH4 is associated with tumor progression, metabolic reprogramming, and immune infiltration. These findings suggest that NXPH4 could serve as a reliable prognostic biomarker and a promising therapeutic target in COAD.

Keywords: Neurexophilin 4 (NXPH4); colon adenocarcinoma (COAD); immune infiltration; metabolic reprogramming; prognosis.