Systematic analyses of the role of prognostic and immunological EIF3A, a reader protein, in clear cell renal cell carcinoma

Abstract

Background Eukaryotic initiation factor 3a (EIF3A), a “reader” protein for RNA methylation, has been found to be involved in promoting tumorigenesis in a variety of cancers. The impact of EIF3A in clear cell renal cell carcinoma (ccRCC) has yet to be reported. This study aimed to identify the prognostic value of EIF3A in ccRCC and investigate the relationship between EIF3A expression and immune infiltration. Methods We collected 29 m6A-related mRNA data and clinicopathological parameters from The Cancer Genome Atlas (TCGA) database. Logistic regression analyses were used to analyse the correlation between EIF3A expression and clinical characteristics. Immunohistochemistry (IHC) was applied to examine EIF3A levels in normal and ccRCC tissues. Univariate and multivariate analyses were conducted to recognize independent factors associated with overall survival (OS) and disease-free survival (DFS). The nomogram aimed to predict the 1-, 3- and 5-year survival probabilities. Gene set enrichment analysis (GSEA) was carried out to determine the potential functions and related signalling pathways of EIF3A expression. To investigate EIF3A of coexpressed genes, we used LinkedOmics, and the results were subjected to enrichment analysis. Simultaneously, LinkedOmics and STRING datasets were used to identify EIF3A coexpressed genes that were visualized via Cytoscape. Finally, we evaluated whether EIF3A expression correlated with the infiltration of immune cells and the expression of marker genes in ccRCC by Tumour Immune Estimation Resource (TIMER) and Gene Expression Profiling Interactive Analysis (GEPIA). Result EIF3A expression was significantly different between ccRCC tissues and normal tissues. EIF3A expression was correlated with poor prognostic clinicopathological factors, and K–M analyses revealed that low EIF3A expression was correlated with a poor prognosis. The results of univariate and multivariate analyses proved that EIF3A was a prognostic factor in ccRCC patients. GSEA results indicated that EIF3A high expression was enriched in the renal cell carcinoma pathway. EIF3A expression was significantly positively correlated with B cells, CD8 + T cells, CD4 + T cells, neutrophils, macrophages, and dendritic cells. Furthermore, EIF3A expression was associated with most marker genes of immune cells. Conclusions EIF3A could serve as a potential biomarker for prognostic and diagnostic stratification of ccRCC and is related to immune cell infiltrates.

Comprehensive analysis of the prognosis and immune infiltration landscape of RNA methylation-related subtypes in pancreatic cancer

“…Reader Eraser M5C TRDMT1 [30], NSUN1 [31], NSUN2 [31] NSUN3 [31], NSUN4 [31], NSUN5 [31] NSUN6 [31], NSUN7 [31], DNMT1 [32] DNMT2 [33], DNMT3A [32], DNMT3B [32] ALYREF [34], YBX1 [34] TET2 [35] M6A METTL3 [36], METTL14 [36], METTL16 [37], WTAP [38], KIAA1429 [39], RBM15 [40], RBM15B [41], ZC3H13 [42] EIF3A [43], IGF2BP1 [44], IGF2BP2 [44], IGF2BP3 [44], YTHDC1 [45], YTHDC2 [45], YTHDF1 [45], YTHDF2 [46], YTHDF3 [47], HNRNPC [48], HNRPA2B1 [44] FTO [49], ALKBH5 [50] M7G METTL1 [51], WDR4 [52] to visualize the coexpression profiles. The coexpression analysis was performed and the heatmap was generated by the R package "corrplot" (version 0.92, method = "circle",insig = "pch", number.cex = 0.5, order = "AOE") [63].…”

Eukaryotic initiation factor 3a promotes the development of diffuse large B-cell lymphoma through regulating cell proliferation

“…Till now, the correlation between eIF3a expression and prognosis in tumors is controversial. Recent studies have shown that eIF3a was highly expressed in esophageal squamous cell carcinoma (ESCC), colorectal cancer and thyroid cancer (TC) [ 16 – 18 ], but lower in clear cell renal cell carcinoma (ccRCC) [ 24 ]. Moreover, eIF3a expression was also related to prognosis of tumor patients.…”

“…Moreover, eIF3a expression was also related to prognosis of tumor patients. In patients with ESCC, ccRCC, low-grade UBC and oral squamous cell carcinoma (OSCC), high levels of eIF3a were associated with favorable prognosis [ 11 , 18 , 24 , 25 ]. Similarly, breast cancer patients with high eIF3a expression were more sensitive to anthracycline drugs and displayed better prognosis [ 26 ].…”

The current landscape of m6A modification in urological cancers

“…In terms of “writers”, The expression of METTL3 ( Zhu et al, 2022 ), WTAP ( Ying et al, 2021 ; He et al, 2021 ) was significantly increased in RCC tissues. The level of METTL14 ( Zhang et al, 2021a ; Liu et al, 2022d ) and eukaryotic initiation factor 3 (eIF3A) ( Zhang et al, 2021b ) in RCC was significantly decreased. The FTO expression was different in various researches, some results show it was upgraded in ccRCC tumors ( Xiao et al, 2020 ; Shen et al, 2022 ).…”

“…In RCC, a study grouped according to 23 m6A regulators found that different groups had different degrees of immune infiltration ( Deng et al, 2022 ). High EIF3A expression upregulated the overall immune infiltration level ( Zhang et al, 2021b ). METTL14 inhibited Tregs infiltration in ccRCC by inhibiting CCL5 ( Xu et al, 2021a ).…”