The correlation between PDIA4 and immunity.
Considering the results from GO and KEGG pathway analysis which elucidated strong connections between PDIA4 and immunological functions, we next performed examinations to confirm this phenomenon. Firstly, we examined the association between expression of PDIA4 and immune scores. The results showed that the PDIA4 expression had relatively lower correlation with both stromal score and immune score in GBM patients (Figure 4A). However, in LGG samples, we could find strong correlation between PDIA4 and stromal or immune scores (Figure 4B). Moreover, we studied the correlation between PDIA4 and 64 non-cancerous cell types to determine the critical cellular components involved in PDIA4 associated immunological process. The results revealed there were 46 cell types were correlated with PDIA4, among which 33 types were positively related whereas 13 types were negatively related (Figure 4C, Table 3). Notably, the cellular components which exhibited dramatic correlation with PDIA4, such as astrocyte, M1 macrophages, CD4+ memory T cells, CD8+ T cells, Tregs and eosinophils have already been demonstrated to play critical roles in the glioma TME. We further validate the correlation between PDIA4 and immune properties via classic immunological markers. The results suggested that PDIA4 was closely related to several immunosuppressive factors, especially the dendritic cell, M2 macrophage, monocyte and T cell exhaustion markers (Table 4). Besides, we subjected PDIA4 to Protein Interaction Analysis (PPI) to study the regulatory network of this protein. Based on the results, we found that PDIA4 could interact with several heat shock proteins (Figure 4D). And the functional study revealed these genes were closely related to stress-reduced responses and endoplasmic reticulum which was consistent with the data described above. Meanwhile, the majority of PDIA4-related genes, such as PDIA6, ERO1LB, ERO1L, HSPA5, HSP90B1 and HYOU1, were found to be tightly involved in the tumor-promoting phenotype.