title: Elevated expression of IFN-inducible CXCR3 ligands predicts poor prognosis in patients with non-metastatic clear-cell renal cell carcinoma.
abstract: 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.
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, China.
authors.forename: Weisi
authors.initials: W
authors.lastname: Liu
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, China.
authors.forename: Yidong
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Fu
authors.affiliation: Department of Urology, Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Department of Urology, Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Chang
authors.affiliation: Department of Urology, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.
authors.forename: Le
authors.initials: L
authors.lastname: Xu
authors.affiliation: Department of Immunology, School of Basic Medical Sciences, Fudan University, Shanghai, China.
authors.forename: Weijuan
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, China.
authors.forename: Jiejie
authors.initials: J
authors.lastname: Xu
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002292:Carcinoma, Renal Cell / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D054357:Chemokine CXCL10 / Q000378:metabolism*; D054371:Chemokine CXCL11 / Q000378:metabolism*; D054370:Chemokine CXCL9 / Q000378:metabolism*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007680:Kidney Neoplasms / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D008024:Ligands; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009364:Neoplasm Recurrence, Local / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D009367:Neoplasm Staging; D009392:Nephrectomy; D011379:Prognosis; D054367:Receptors, CXCR3 / Q000378:metabolism*; D012189:Retrospective Studies; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor; C114753:CXCL10 protein, human; C515202:CXCL11 protein, human; C080810:CXCL9 protein, human; C515187:CXCR3 protein, human; D054357:Chemokine CXCL10; D054371:Chemokine CXCL11; D054370:Chemokine CXCL9; D008024:Ligands; D054367:Receptors, CXCR3
keywords: CXCL10; CXCL11; CXCL9; clear-cell renal carcinoma; prognostic factor