The Potential Impact of HNRNPA2B1 on Human Cancers Prognosis and Immune Microenvironment

Abstract

HNRNPA2B1 is a member of the HNRNP family, which is associated with telomere function, mRNA translation, and splicing, and plays an important role in tumor development. To date, there have been no pan-cancer studies of HNRNPA2B1, particularly within the TME. Therefore, we conducted a pan-cancer analysis of HNRNPA2B1 using TCGA data. Based on datasets from TCGA, TARGET, Genotype-Tissue Expression, and Human Protein Atlas, we employed a range of bioinformatics approaches to explore the potential oncogenic role of HNRNPA2B1. This included analyzing the association of HNRNPA2B1 expression with prognosis, tumor mutation burden (TMB), microsatellite instability (MSI), immune response, and immune cell infiltration of individual tumors. We further validated the bioinformatic findings using immunohistochemistry techniques. HNRNPA2B1 was found to be differentially expressed across most tumor types in TCGA's pan-cancer database and was predictive of poorer clinical staging and survival status. HNRNPA2B1 expression was also closely linked to TMB, MSI, tumor stemness, and chemotherapy response. HNRNPA2B1 plays a significant role in the TME and is involved in the regulation of novel immunotherapies. Its expression is significantly associated with the infiltration of macrophages, dendritic cells, NK cells, and T cells. Furthermore, HNRNPA2B1 is closely associated with immune checkpoints, immune-stimulatory genes, immune-inhibitory genes, MHC genes, chemokines, and chemokine receptors. We performed a comprehensive evaluation of HNRNPA2B1, revealing its potential role as a prognostic indicator for patients and its immunomodulatory functions.

Figure 1

Pan-cancer HNRNPA2B1 expression: (a) pan-cancer expression of HNRNPA2B1 between tumor tissues and normal tissues. Pan-cancer paired HNRNPA2B1 expression. (b–o) Pan-cancer differential expression of HNRNPA2B1 in paired tumor and adjacent normal tissues in indicated tumor types from TCGA and TARGET database, (b) TCGA-STAD; (c) TCGA-BLCA; (d) TCGA-BRCA; (e) TCGA-CHOL; (f) TCGA-COAD; (g) TCGA-ESCA; (h) TCGA-HNSC; (i) TCGA-READ; (j) TARGET-WT; (k) TCGA-LIHC; (l) TCGA-LUSC; (m) TCGA-THCA; (n) TCGA-KICH; and (o) TCGA-KIRC. (p) Relative qPCR expression levels of HNRNPA2B1 in HA1800, HS683, U251, and A172 cells.  ^∗p < 0.05;  ^∗∗p < 0.01;  ^∗∗∗p < 0.001; and  ^∗∗∗∗p < 0.0001; –, not significant.

Figure 2

The expression of HNRNPA2B1 was detected by immunohistochemistry and the subcellular location of HNRNPA2B1 was detected by immunofluorescence. Immunohistochemical results from HPA database: (a) breast cancer; (b) cervical cancer; (c) colorectal cancer; (d) endometrial cancer; (e) GBM; (f) head and neck cancer; (g) liver cancer; (h) lung cancer; (i) lymphoma; (j) melanoma; (k) ovarian cancer; (l) pancreatic cancer; (m) prostate cancer; (n) skin cancer; (o) stomach cancer; (p) testis cancer; (q) urothelial cancer; (r) KIRC; immunofluorescence results: (s) GL261, (t) MDA-MB-231; immunofluorescence results from HPA database: (u) U251-MG; (v) A-431; (w) A549; (x) PC-3; (y) U-2 OS; and (z) SH-SY5Y.

Figure 3

Kaplan–Meier survival of HNRNPA2B1 expression: (a–e) pan-cancer Kaplan–Meier OS, DSS, DFI, and PFI of HNRNPA2B1 in indicated tumor types from TCGA database. (a) ACC; (b) LGG + BGM; (c) KICH + KIRP; (d) LUAD + CESC; and (e) LIHC. The median value of HNRNPA2B1 in each tumor was taken as the cut-off value.

Figure 4

Relationship between HNRNPA2B1 expression and mutation landscape, RNA modifications: (a) STAD; (b) COAD; (c) CESC; (d) LGG + GBM; (e) LIHC; (f) LUAD; and (g) RNA modification. The median value of HNRNPA2B1 in each tumor was taken as the cut-off value.  ^∗p < 0.05;  ^∗∗p < 0.01; and  ^∗∗∗p < 0.001.

Figure 5

Analysis of the relationship between HNRNPA2B1 expression and tumor microenvironment: (a) the correlation between HNRNPA2B1 and infiltration level of IMMUNE cells using TIMER database; (b) the correlation between HNRNPA2B1 and IPS; (c) the correlation between HNRNPA2B1 and immune regulatory genes; and (d) the correlation between HNRNPA2B1 and immune checkpoint genes.  ^∗p < 0.05;  ^∗∗p < 0.01; and  ^∗∗∗p < 0.001.

Figure 6

Correlation analysis between ESTIMATE scores and HNRNPA2B1 expression. The correlation between ESTIMATEscore, immunescore, stromalscore, and HNRNPA2B1: (a) ACC; (b) BRCA; (c) LUAD; (d) LUSC; (e) STES; and (f) STAD. The correlation between immunetherapy, tumor stemness, and HNRNPA2B1: (g) TMB; (h) MSI; (i) Stemness; and (j) HRD.

Figure 7

GSEA of HNRNPA2B1 in pan-cancer: (a) BLCA; (b) CHOL; (c) DLBC; (d) KICH; (e) KIRP; and (f) READ.