Clinical significance of IFIT2 expression in human renal cancer tissues

Abstract

Background: Interferon (IFN)-induced protein with tetratricopeptide repeats 2 (IFIT2) is an important member of the IFN-stimulated gene (ISG) family. It has been demonstrated that IFIT2 is important in the physiopathological processes of antiviral and antitumor activities. We previously demonstrated that IFIT2 was highly expressed in paracarcinoma tissues compared with gastric cancer tissues, and its expression level was positively correlated with a superior postoperative prognosis of the patients.

Methods: We performed immunohistochemical staining of IFIT2 in human clear cell renal cell carcinoma (ccRCC) tissues by using a tissue microarray. RNAseq data of kidney clear cell carcinoma (KIRC) samples from The Cancer Genome Atlas (TCGA) were used to perform the enrichment analyses based on the genes that were highly correlated with IFIT2.

Results: Weak staining of IFIT2 was located on the cytoplasm and cell membrane surface of the cancer cells, while positive staining of IFIT2 was located mainly on adjacent normal tissues. Survival analysis showed that patients with higher IFIT2 expression had better overall survival than patients with lower IFIT2 expression (P=0.030). The Cox model further demonstrated that age (P=0.002), pathological stage (P=0.000), TNM stage (P=0.005) and IFIT2 expression (P=0.003) could be used as independent prognostic predictors for ccRCC patients. Additionally, the enrichment analysis based on ccRCC expression profile data extracted from TCGA revealed that the genes highly correlated with IFIT2 were mainly related to the biological processes of virus response, T cells and the innate immune response (GO:0009615, GO:0042110, and GO:0045088) and the pathways of NLR signaling, chemokine signaling, and TLR signaling (hsa04621, hsa04062, and hsa04620).

Conclusions: IFIT2 could serve as a potential prognostic marker for ccRCC patients, and the mechanism of decreased IFIT2 expression in the progression of ccRCC merits further investigation.

Keywords: Renal cancer; immunohistochemistry; interferon-induced protein with tetratricopeptide repeats 2 (IFIT2); tissue microarray.

Figure 1

IFIT2 staining in human ccRCC tissues and normal tissues. Positive immunostaining of IFIT2 could be detected in the cytoplasm of cancer cells in ccRCC tissues or of renal tubular epithelial cells in normal tissues. IFIT2, interferon (IFN)-induced protein with tetratricopeptide repeats 2; ccRCC, clear cell renal cell carcinoma.

Figure 2

Prognostic value of IFIT2 staining in ccRCC tissues. (A) The expression level of IFIT2 in renal cancer tissues was significantly lower than that in adjacent normal tissues (P<0.001); (B) higher IFIT2 expression in ccRCC tissues was significantly associated with better patient survival (HR: 0.428, 95% CI: 0.199–0.923, P=0.030); (C,D) based on TCGA gene profile data from http://gepia.cancer-pku.cn/, our results revealed that decreased IFIT2 mRNA expression in ccRCC tissues was significantly correlated with poor OS and DFS in patients (P=0.017 and P=0.11, respectively). IFIT2, interferon (IFN)-induced protein with tetratricopeptide repeats 2; ccRCC, clear cell renal cell carcinoma; TCGA, The Cancer Genome Atlas; OS, overall survival; DFS, disease-free survival.

Figure 3

Enrichment analysis of IFIT2 and its highly correlated genes. Functional enrichment analysis of IFIT2 and its correlated genes was performed by the R package “clusterProfiler”. (A) The top 20 enriched biological processes of IFIT2 and its correlated genes; (B) enrichment map of the relationships between the top 20 enriched biological processes; (C) the top 20 enriched pathways of IFIT2 and its correlated genes; (D) enrichment map of the relationships between the top 20 enriched pathways. IFIT2, interferon (IFN)-induced protein with tetratricopeptide repeats 2.