NAV3 Is a Novel Prognostic Biomarker Affecting the Immune Status of the Tumor Microenvironment in Colorectal Cancer

Abstract

Colorectal cancer (CRC) is one of the most common malignant tumors in the world. Tumor microenvironment (TME) plays a crucial role in the development of CRC. With the deep understanding of TME function, growing studies have demonstrated that alteration in tumor-infiltrating immune cells (TICs) and gene expressions are associated with clinical outcomes of various tumors. In this study, we aimed to recognize critical prognostic genes involved in immune states in TME of CRC. Hence, the proportion of TICs and the number of immune and stromal components in CRC samples from TCGA datasets were calculated by the use of CIBERSORT and ESTIMATE calculation methods. Different assays were applied to collect differential expression genes (DEGs) shared by the ImmuneScore and StromalScore. DEGs were further analyzed by the use of univariate Cox regression. Our attention focused on neuron navigator 3 (NAV3) which was highly expressed in CRC specimens and associated with an advanced clinical stage and poor prognosis of CRC patients. KEGG assays revealed that NAV3 may be involved in Alzheimer disease, amyotrophic lateral sclerosis, Huntington disease, FoxO signaling pathway, and human papillomavirus infection. Correlation assays showed that macrophage M0 and B cells memory, NK cells activated, dendritic cells resting, T cells CD4 memory activated, and T cells CD8 were correlated with NAV3 expression, indicating that NAV3 may represent the immune status of TME. Finally, RT-PCR confirmed that NAV3 expression was distinctly increased in CRC cells, and its knockdown suppressed the proliferation of CRC cells. Overall, NAV3 could be used as a novel predictor for TME of CRC and might be a novel prognostic biomarker. In the future, drugs targeting NAV3 might be developed as a potential immunotherapy for CRC patients.

Cancer-associated fibroblast-related gene signatures predict survival and drug response in patients with colorectal cancer

“…The biological functions of these genes involved in our signature have been elucidated more or less in previous studies. It was shown that the high levels of ZNF385A, LAMP, CADM3, NAV3, and NLGN1 indicate the poor prognosis of CRC patients (Martinez-Romero et al, 2018;Chang et al, 2021;Chen et al, 2021;Yu et al, 2021;Li et al, 2022), and these results were in accordance with our findings. Similarly, low expressions of CYTH3, NOVA1, and EPHA6 were highly correlated with longer OS in patients with other types of cancers (Zhang et al, 2014;Zhou et al, 2018;Xu et al, 2022).…”

SARS-CoV-2 infection severity and mortality is modulated by repeat-mediated regulation of alternative splicing

“…3E to J ). SRRM4 is a known regulator of alternative splicing, while NAV3 is reported to be involved in multiple immune and infection-associated pathways such as FoxO signaling, T cell activation, and Human papillomavirus infection pathways ( 24 , 25 ). Therefore, we propose that the promoter region may play an important role in shaping the alternative transcription vis-à-vis disease severity in COVID-19 disease.…”

“…However, recent studies have reported association in some other diseases as well. For example, SRRM4 and NAV3 are reported to regulate lung cancer and colorectal cancer, respectively ( 24 , 45 ). The European Molecular Biology Laboratory (EMBL) expression atlas shows their expression in different tissues, such as non-endothelial lung cells as well as other tissues in the lungs and gastrointestinal tract, in addition to the neuronal tissues.…”