AUTHOR=Deng Jiehua , Xiao Wei , Wang Zheng 

TITLE=FAM46C as a Potential Marker for Pan-Cancer Prognosis and Predicting Immunotherapeutic Efficacy

JOURNAL=Frontiers in Genetics

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2022.810252

DOI=10.3389/fgene.2022.810252

ISSN=1664-8021

ABSTRACT=<p><bold>Background:</bold><italic>FAM46C</italic> is a common mutated gene in tumours. A comprehensive understanding of the relationship between <italic>FAM46C</italic> expression and pan-cancer can guide clinical prognosis and broaden the immunotherapeutic targets.</p><p><bold>Methods:</bold> Data from The Cancer Genome Atlas and Genotype-Tissue Expression (GTEx) databases were obtained, and gene expression of different tumour types and stages was analysed. Immunohistochemical analysis was performed to detect differences in the <italic>FAM46C</italic> protein levels in normal and cancerous tissues. The genetic variation of <italic>FAM46C</italic> was characterised using cBioPortal. The clinical prognostic value of <italic>FAM46C</italic> and the impact of <italic>FAM46C</italic> expression levels on the prognosis of patients with different types of cancer were assessed based on Kaplan–Meier and Cox regression analyses. Gene set enrichment analysis (GSEA) was used to analyse the pathways associated with <italic>FAM46C</italic>. Correlations between <italic>FAM46C</italic> expression levels and immune infiltration were assessed using the TIMER2 database and CIBERSORT algorithm, and correlations between <italic>FAM46C</italic> expression and the ESTIMATE, immune and stromal scores were analysed using the ESTIMATE algorithm. In addition, we also analysed the correlation between <italic>FAM46C</italic> expression and immune activation, suppression genes and immune chemokines.</p><p><bold>Results:</bold> The expression level of <italic>FAM46C</italic> was correlated with the prognosis of most tumours, and low expression levels often suggested a poor prognosis. <italic>FAM46C</italic> was positively correlated with the abundance of CD4<sup>+</sup> T cells, CD8<sup>+</sup> T cells and plasma B lymphocytes in the tumour microenvironment. <italic>FAM46C</italic> exhibited a strong correlation with immunomodulatory pathways, immunomodulatory factors and immune markers. In addition, high <italic>FAM46C</italic> expression correlated with tumour mutational burden in acute myeloid leukaemia and microsatellite instability in endometrial cancer.</p><p><bold>Conclusion:</bold> Our study suggests that <italic>FAM46C</italic> can be a potential prognostic marker for pan-cancer, is closely associated with immune regulation and may be an immune checkpoint to guide future clinical immunotherapy.</p>