A five-protein prognostic signature with GBP2 functioning in immune cell infiltration of clear cell renal cell carcinoma

Kun Meng; Yu-Ying Li; Dan-Ya Liu; Li-Ling Hu; Yun-Long Pan; Chris Zhiyi Zhang; Qing-Yu He

doi:10.1016/j.csbj.2023.04.015

A five-protein prognostic signature with GBP2 functioning in immune cell infiltration of clear cell renal cell carcinoma

Comput Struct Biotechnol J. 2023 Apr 17:21:2621-2630. doi: 10.1016/j.csbj.2023.04.015. eCollection 2023.

Authors

Kun Meng^{1

2}, Yu-Ying Li², Dan-Ya Liu², Li-Ling Hu², Yun-Long Pan¹, Chris Zhiyi Zhang², Qing-Yu He^{1

2}

Affiliations

¹ The First Affiliated Hospital of Jinan University, Jinan University, Guangzhou 510632, China.
² MOE Key Laboratory of Tumor Molecular Biology and Key Laboratory of Functional Protein Research of Guangdong Higher Education Institutes, Institute of Life and Health Engineering, College of Life Science and Technology, Jinan University, Guangzhou 510632, China.

Abstract

Clear cell renal cell carcinoma (ccRCC) is of poor clinical outcomes, and currently lacks reliable prognostic biomarkers. By analyzing the datasets of the Cancer Genome Atlas (TCGA) and the Clinical Proteomic Tumor Analysis Consortium (CPTAC), we established a five-protein prognostic signature containing GBP2, HLA-DRA, ISG15, ISG20 and ITGAX. Our data indicate that this signature was closely correlated with advanced stage, higher pathological grade, and unfavorable survivals in patients with ccRCC. We further functionally characterized GBP2. Overexpression of GBP2 enhanced the phosphorylation of STAT2 and STAT3 to trigger JAK-STAT signaling and promote cell migration and invasion in ccRCC. Treatment of Ruxolitinib, a specific inhibitor of JAK/STAT, attenuated the GBP2-mediated phenotypes. Patients with high GBP2 expression were accompanied with more infiltration of immune cells positively stained with CD3, CD8, CD68, and immune checkpoint markers PD-1 and CTLA4, which was validated by Opal multiplex immunohistochemistry in ccRCC tissues. More CD8 + T cells and CD68 + macrophages were observed in patients expressing high GBP2. Taken together, a five-protein prognostic signature was constructed in our study. GBP2 has an oncogenic role via modulating JAK-STAT signaling and tumor immune infiltration, and thus may serve as a potential therapeutic target in ccRCC.

Keywords: Clear cell renal cell carcinoma; GBP2; Immune-cell infiltration; Prognostic signature.