Research Papers:

Elevated expression of IFN-inducible CXCR3 ligands predicts poor prognosis in patients with non-metastatic clear-cell renal cell carcinoma

Weisi Liu, Yidong Liu, Qiang Fu, Lin Zhou, Yuan Chang, Le Xu, Weijuan Zhang _ and Jiejie Xu

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Oncotarget. 2016; 7:13976-13983. https://doi.org/10.18632/oncotarget.7468

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Weisi Liu1, Yidong Liu1, Qiang Fu1, Lin Zhou2, Yuan Chang2, Le Xu3, Weijuan Zhang4, Jiejie Xu1

1Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, China

2Department of Urology, Zhongshan Hospital, Fudan University, Shanghai, China

3Department of Urology, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China

4Department of Immunology, School of Basic Medical Sciences, Fudan University, Shanghai, China

Correspondence to:

Weijuan Zhang, e-mail: [email protected]

Jiejie Xu, e-mail: [email protected]

Keywords: clear-cell renal carcinoma, CXCL9, CXCL10, CXCL11, prognostic factor

Received: October 26, 2015     Accepted: February 05, 2016     Published: February 17, 2016


IFN-inducible CXCR3 ligands (ICL), namely CXCL9, CXCL10 and CXCL11, exhibit pleiotropic roles in orchestrating immunity and angiogenesis. However, the prognosis value of them in renal cell carcinoma (RCC) was still obscure. Thus, we retrospectively used immunohistochemistry approach to evaluate the impact of these ligands on recurrence and survival of non-metastatic clear cell RCC (ccRCC) patients after nephrectomy. We systemically built a prespecified ICL score based on these ligands, and found specimens with high ICL score were prone to possess high Fuhrman grade, necrosis, and high-risk level of SSIGN. Moreover, ICL score stratified patients into different risk subgroups, and remained an independent adverse prognosticator for overall survival (OS) and recurrence-free survival (RFS). Meanwhile, in TCGA database, the increasing ICL mRNA predicted poor survival and early recurrence. Furthermore, after adding ICL score into SSIGN, the C-index for OS and RFS increased from 0.705 to 0.746 and 0.712 to 0.765, respectively. In conclusion, the ICL score based on expression of CXCL9, CXCL10 and CXCL11 stratified non-metastatic ccRCC patients into different risk subgroups of recurrence and death, which might benefit preoperative risk stratification and guide immune therapy in the future.

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