Identification of PSMD7 as a prognostic factor correlated with immune infiltration in head and neck squamous cell carcinoma

Abstract

Background: Recurrent locally advanced or metastatic head and neck squamous cell carcinoma (HNSCC) is associated with dismal prognosis because of its highly invasive behavior and resistance to conventional intensive chemotherapy. The identification of effective markers for early diagnosis and prognosis is important for reducing mortality and ensuring that therapy for HNSCC is effective. Proteasome 26S subunit, non-ATPase 7 (PSMD7) is an ATP-independent component of the 19S regulatory subunit. The prognostic value of PSMD7 and the association with immune infiltration in HNSCC remains unclear.

Methods: The Sangerbox, Oncomine, UALCAN and Human Protein Atlas (HPA) databases were used to examine PSMD7 expression profiles in HNSCC. The CVCDAP was used to analysis the association of PSMD7 with the prognosis of patients with HNSCC. The mechanism was investigated with gene set enrichment analysis (GSEA). The association between expression of PSMD7 and immune infiltration in HNSCC was investigated using the Tumor Immune Estimation Resource (TIMER), TISIDB database and CIBERSORT algorithm.

Results: PSMD7 expression was significantly up-regulated in HNSCC compared with relative normal tissues. In addition, up-regulated PSMD7 expression was associated with various clinicopathological parameters. High expression of PSMD7 suggested inferior survival of HNSCC patients. GSEA and CERES score indicated that PSMD7 was closely correlated with tumor-related signaling pathways and cell survival. Functional analyses revealed that PSMD7 was positively correlated with various infiltration levels. Moreover, PSMD7 influenced the prognosis of HNSCC patients partially via immune infiltration.

Conclusion: Our findings suggest that PSMD7 is associated poor prognosis in patients with HNSCC and plays an important role in tumor-related immune infiltration.

Keywords: HNSCC; OS; PSMD7; immune infiltration; prognostic factor.

Figure 1. The expression of PSMD7 was higher in HNSCC

(A) Expression of PSMD7 in HNSCC tissues compared with that in normal tissues from the UALCAN database. Box plots comparing PSMD7 expression in HNSCC patients and normal individuals were obtained from the analysis of Toruner Head-Neck (B), Ye Head-Neck (C) and Pyeon Muti-cancer (D) in Oncomine database. The protein expression of PSMD7 expression in HNSCC tissues and normal tissues were detected in the HPA database. IHC staining was performed by using (E) CAB019379 and (F) HPA056069 antibodies. CERES score was used to evaluate the importance of PSMD7 for cell survival of HNSCC. (G) CERES score approach to 0 means the gene is not an essential gene for cell survival, while score approach to −1 means the gene is an essential gene. **, P<0.01; ***, P<0.001.

Figure 2. High mRNA expression of PSMD7 indicates poor prognosis in HNSCC patients

PSMD7 expression was analyzed in different (A) tumor grades (from grade 1 to 4), (B) races, (C) HPV infection statues and (D) TP53 mutation status. Prognostic values of (E) OS, (F) DSS and (G) PFI in HNSCC patients were analyzed based on mRNA expression of PSMD7 using Kaplan–Meier plotter. (H) Forest plots showing the association between PSMD7 expression and clinicopathological features in HNSCC patients. *, P<0.05; **, P<0.01; ***, P<0.001.

Figure 3. Interaction analysis of PSMD7 at the gene and protein levels

(A) The gene–gene interaction network for PSMD7was analyzed using the GeneMANIA database. The 20 most frequently changed neighboring genes are shown. Each node represents a gene. The node color represents the possible functions of the respective gene. (B) The PPI network, which contained 11 nodes and 38 edges, was constructed using the STRING database. (C) Scatterplots of correlations between PSMD7 expression and PSMD11, PSMA6, PSMC1, PSMC4 and PSMD8 in HNSCC. Tumor-associated pathway determined by GSEA analysis based on PSMD7 expression (D).

Figure 4. Association of PSMD7 expression with immune infiltration levels in HNSCC

(A) The association between PSMD7 expression and infiltration levels of B cells, CD4⁺ T cells, CD8⁺ T cells, macrophages, neutrophils and dendritic cells in the TIMER database. (B) Pairwise relationship between immune cell abundance ratios. The numerical values represent the correlation value. (C) immune cell distribution based on PSMD7 expression was analyzed with the CIBERSORT algorithm.

Figure 5. Prognostic analysis of the high and low PSMD7 expression based on immune cell subgroups in HNSCC

(A–L) Correlations between PSMD37 in different immune cell subgroups and OS in HNSCC patients were estimated by the CIBERSORT algorithm.