GBP5表現量變化:對於腎臟亮細胞癌的惡性進展

以及預測Atezolizumab反應的潛在生物標記

林嘉緯¹﹐吳佳璋¹﹐江怡德¹﹐胡書維¹﹐林源峰²

1 衛生福利部雙和醫院 2 台北醫學大學臨床醫學研究所

GBP5 Upregulation Contributes to Malignant Progression and Serves as a Potential Biomarker for Predicting a Favorable Response to Atezolizumab in Clear Cell Renal Cell Carcinoma

Chia-Wei Lin,¹ Chia-Chang Wu,¹ Yi-Te Chiang^1,Su-Wei Hu,¹ Yuan-Feng Lin²

1Department of Urology, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan.

2Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan

Purpose:

Clear cell renal cell carcinoma (ccRCC) is the most common subtype of RCC and usually associated with a poorer prognosis. Therefore, identifying a useful biomarker to predict therapeutic responsiveness and understanding the molecular mechanism for metastatic progression is urgently needed for the precise management of ccRCC.

Materials and Methods:

The Cancer Genome Atlas (TCGA) was used to perform transcriptional profile of guanylate binding protein 5 (GBP5) in RCC subtypes. Kaplan-Meier analysis and Cox regression test were used to evaluate the prognostic significance of GBP5. Gene set enrichment analysis (GSEA) was performed to determine the mechanism for the GBP5-promoted ccRCC progression.

Results:

Results: Transcriptional profiling revealed that GBP5 upregulation is predominantly detected in primary tumors compared to normal tissues derived from ccRCC in comparison with other RCC subtypes and highly correlates with a poorer prognosis in TCGA ccRCC cohort. Cell-based assays demonstrated that GBP5 expression is positively associated with cell growth rate and migration ability in ccRCC cells. GSEA simulation indicated that GBP5 upregulation strongly correlates with the activation of interferon gamma (IFNg)-responsive pathway in primary tumors derived from ccRCC patients stratified as GBP5 high expression/cancer progression in Kaplan-Meier analyses. Importantly, GBP5 upregulation was appeared to positively correlate with programmed cell death-ligand 1 (PD-L1) expression in TCGA ccRCC samples and predicted a favorable response to Atezolizumab, PD-L1 antibody, in patients with urinary cancers, including RCC.

Conclusion:

GBP5 upregulation may associate with the mechanism for malignant evolution and sever as a useful biomarker to predict the anti-cancer effectiveness of Atezolizumab on ccRCC.