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Clinical significance of IFIT2 expression in human renal cancer tissues

Bin Xu^1,2,3, Yu-Lan Zhu^1,2,3, Jia-Lin Fan^1,2,3,4

¹Department of Tumor Biological Treatment, the Third Affiliated Hospital of Soochow University, Changzhou 213003, China.

Translational Cancer Research

|February 4, 2022

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.

Insights

Interferon-induced protein with tetratricopeptide repeats 2 (IFIT2) is a potential prognostic marker for clear cell renal cell carcinoma (ccRCC). Lower IFIT2 expression in ccRCC tissues correlates with poorer patient survival, suggesting a role in cancer progression.

Area of Science:

Oncology
Immunology

Background:

Interferon (IFN)-induced protein with tetratricopeptide repeats 2 (IFIT2) is an IFN-stimulated gene (ISG) involved in antiviral and antitumor activities.
Previous studies indicated IFIT2's high expression in paracarcinoma tissues and its correlation with better prognosis in gastric cancer patients.

Purpose of the Study:

To investigate the prognostic value of IFIT2 in human clear cell renal cell carcinoma (ccRCC).
To explore the biological pathways associated with IFIT2 expression in ccRCC.

Main Methods:

Immunohistochemical staining of IFIT2 in ccRCC tissues.
Analysis of The Cancer Genome Atlas (TCGA) RNAseq data for kidney clear cell carcinoma (KIRC) samples.
Enrichment analyses of genes correlated with IFIT2 expression.

Main Results:

IFIT2 staining was weaker in ccRCC cancer cells compared to adjacent normal tissues.
Higher IFIT2 expression was significantly associated with better overall survival in ccRCC patients (P=0.030).
IFIT2 expression, along with age, pathological stage, and TNM stage, were independent prognostic predictors for ccRCC (P=0.003).
Genes correlated with IFIT2 were linked to virus response, T cells, innate immunity, NLR, chemokine, and TLR signaling pathways.

Conclusions:

IFIT2 shows potential as a prognostic marker for ccRCC patients.
Further research is needed to understand the mechanism behind decreased IFIT2 expression during ccRCC progression.

Read full analysis

Keywords:

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

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