Elevated of NDUFA4L2 expression in colon adenocarcinoma is correlated with an unfavorable prognosis and increased immune cell infiltration

Qingbu Mei; Ping Chen; Ying Lv; Lihong Zheng; Dan Liu; Minglong Zhang; Wanquan Liu; Penghui Li

doi:10.1016/j.heliyon.2024.e25462

Elevated of NDUFA4L2 expression in colon adenocarcinoma is correlated with an unfavorable prognosis and increased immune cell infiltration

Heliyon. 2024 Jan 29;10(3):e25462. doi: 10.1016/j.heliyon.2024.e25462. eCollection 2024 Feb 15.

Authors

Qingbu Mei¹, Ping Chen², Ying Lv³, Lihong Zheng¹, Dan Liu¹, Minglong Zhang¹, Wanquan Liu¹, Penghui Li¹

Affiliations

¹ Department of Medical Genetics, Qiqihar Medical University, Qiqihar 161006, China.
² Department of Cell Biology, Qiqihar Medical University, Qiqihar 161006, China.
³ Department of Basic Medical Research Center, Qiqihar Medical University, Qiqihar 161006, China.

Abstract

Background: Colon adenocarcinoma (COAD) is a prevalent malignancy worldwide, yet, its underlying pathogenesis and genetic characteristics are still unclear. Previous studies have suggested that NADH dehydrogenase 1 alpha subcomplex subunit 4-like 2 (NDUFA4L2) may affect tumor progression across various cancers. However, this effect on COAD has rarely been reported. Thus, this study investigated NDUFA4L2's prognostic and diagnostic relevance and explored its potential connection with immune cell infiltration in COAD.

Methods: To achieve this, RNA sequencing data from Cancer Genome Atlas (TCGA) was analyzed to assess NDUFA4L2's prognostic value in COAD, and factors relevant to the prognosis of COAD, including NDUFA4L2, were scrutinized using Kaplan-Meier analyses as well as univariate and multivariate Cox regression. A nomogram model was created to project prognosis based on the results of multivariate Cox analysis. Furthermore, gene set enrichment analysis (GSEA) was employed to pinpoint key NDUFA4L2-related pathways, and single-sample GSEA (ssGSEA) on TCGA data was employed to investigate the connections of NDUFA4L2 with cancer immune infiltrations.

Results: Our findings revealed significant associations of high NDUFA4L2 expression with poor overall survival, progression-free interval, and disease-specific survival of COAD patients. GSEA indicated close links of NDUFA4L2 with several signaling pathways implicated in tumorigenesis, including extracellular matrix receptor interaction, the intestinal immune network for immunoglobulin A production, natural killer (NK) cell-mediated cytotoxicity, pathways in cancer, cell adhesion molecules, mitogen-activated protein kinase signaling pathway, Hedgehog signaling pathway, transforming growth factor beta signaling pathway, and chemokine signaling pathway. Additionally, ssGSEA identified a positive link between increased NDUFA4L2 expression and higher infiltration degree of various immune cells, such as immature dendritic cells, macrophages, NK cells and dendritic cells.

Conclusions: Collectively, our findings demonstrate the association of increased NDUFA4L2 expression with adverse prognosis and heightened immune cell infiltration in COAD patients.

Keywords: COAD; NDUFA4L2; Prognosis; Tumor immune infiltration.