Prognostic Value and Immunological Role of POP7 in Clear Cell Renal Cell Carcinoma

Abstract

Background: Studies have found that RNA-binding proteins (RBPs) are participated in the occurrence or development of tumours. However, the role of processing of precursor family (POP family) in clear cell renal cell carcinoma (ccRCC) has not been studied yet. Here, we analyzed the expression and prognostic value of POP family in ccRCC analyzed and subsequently revealed the relationship between POP7 and immune infiltration in ccRCC patients.

Methods: POP family expression in cancer and normal tissues was analyzed in Cancer Genome Atlas pan-cancer (TCGA-pan-cancer). Kaplan-Meier (KM) survival analysis, univariable and multivariable analysis demonstrated the survival of ccRCC with POP family in Kidney Clear Cell Carcinoma (TCGA-KIRC). POP7 mRNA and protein expression were verified by Gene Expression Omnibus (GEO) data, the quantitative real-time polymerase chain reaction (qRT-PCR), and Office of Cancer Clinical Proteomics Research (CPTAC). The diagnostic ability of POP7 mRNA and protein expression was achieved with ROC curves. Gene Set Enrichment Analysis (GSEA) and TiMER2 evaluated pathogenesis role and immune infiltration of POP7in ccRCC.

Results: There is a significant difference in expression of POP family in TCGA-pan-cancer, especially in ccRCC. KM survival analysis, univariable and multivariable analysis demonstrated low expression of POP7 and was associated with poor OS and poor DFS. GEO data, the qRT-PCR, and CPTAC verified the high expression of POP7 mRNA and protein in ccRCC. ROC curves verified a valuable diagnostic ability of POP7 in mRNA and protein expression. GSEA demonstrated POP7 was associated with CD8+cells, CD4+cells, natural killer (NK) cells, and helper T (TH1) cells. TiMER2 results indicated POP7 had a positive correlation with T cell regulatory (Tregs) and myeloid-derived suppressor cells (MDSC) in ccRCC and was an immunosuppressor for ccRCC.

Conclusion: POP7 was a reliable immunosuppressor, predictor and biomarker for ccRCC.

Keywords: POP7; ccRCC; immunotherapy; prognostic indicator.

Figure 1

POP family expression in TCGA-KIRC datasets. (A) Heat map depicting POP family expression in TCGA-KIRC (n = 605). (B) and (C) POP1, POP4, and POP7 had a higher expression, while POP5 had a lower expression in paired ccRCC tissues vs non-tumorous tissues (Normal n = 72, Tumour n = 533). (D) and (E) POP1, POP4, and POP7 had a higher expression, while POP5 had a lower expression in paired ccRCC tissues vs non-tumorous tissues (Normal n = 72, Tumour n = 72). Research. ***P <0.001.

Figure 2

Prognostic significance of POP family in ccRCC. (A) and (B) Higher POP 4 had shorter OS and DFS than the lower expressers. (C) and (D) Higher POP 5 had shorter OS and DFS than the lower expressers. (E) and (F) Higher POP 7 had shorter OS and DFS than the lower expressers.

Figure 3

The relationship between clinical characteristics and POP7 in KIRC. (A) Survival status. (B) disease free status. (C) M stage. (D) N stage. (E) and (F) T stage. (G) and (H) grade. (I) and (J)TNM stage. *P <0.05, and ***P <0.001.

Figure 4

Verification of POP7 in ccRCC patients. (A) POP7 mRNA was higher in ccRCC cancer tissue from GSE16441. (B) POP7 mRNA was higher in ccRCC cancer samples. (C and D) The mRNA expression of paired and total POP7 exhibited higher in cancer samples from CPTAC database. (E) and (F) The protein expression of paired and total POP7 exhibited higher in cancer samples from CPTAC database. ***P <0.001.

Figure 5

The diagnostic value of POP7 in ccRCC. (A) and (B) ROC curve of POP7 mRNA between total and paired tumor and non-cancerous normal tissues in TCGA-KIRC, the AUC: 0.8260 and 0.8807 (p < 0.001); (C) The AUC of POP7 mRNA between tumor and paired non-cancerous normal tissues in GSE16441 was 0.7226 (p=0.024). (D) The AUC of POP7 mRNA between tumor and paired non-cancerous normal tissues in clinical samples was 0.6753 (p = 0.036). (E) and (F) ROC curve of POP7 mRNA between total and paired tumor and non-cancerous normal tissues in CPTAC, the AUC: 0.9376 and 0.9680 (p < 0.001). (G) and (H) ROC curve of POP7 protein between total and paired tumor and non-cancerous normal tissues in CPTAC, the AUC: 0.8594 and 0.8554 (p < 0.001).

Figure 6

Pathway of POP7 in TCGA-KIRC with Gene Set Enrichment Analysis (GSEA). POP7 had a positive correlation with downregulation of CD4+cells (A), CD8+cells (B), natural killer (NK) cells (C). Upregulation role of POP7 in helper T (TH1) cells (D). POP7 had a negative correlation with upregulation of CD4+cells (E), CD8+cells (F and G), natural killer (NK) cells (H).

Figure 7

TiMER2 results of POP7 and immune infiltration in ccRCC. POP7 had a positive correlation with Tregs (A and B), and MDSC (C) in ccRCC. POP7 had a negative correlation with CD4+cells (D–G), CD8+cells(H), natural killer (NK) cells (I) in ccRCC.