title: Identification and validation of an eight-gene expression signature for predicting high Fuhrman grade renal cell carcinoma.
abstract: Clear cell renal cell carcinoma (ccRCC) is a malignancy with heterogeneous outcomes. Currently, renal mass biopsies are commonly employed to extract disease characteristics and aid prognosis. Although the pathological diagnosis of malignant disease is accurate in contemporary reports, the classification of Fuhrman grade using biopsy specimens remains far from promising. To generate a gene signature to distinguish high-grade ccRCC, we used the cancer genome atlas (TCGA) database to develop a gene expression signature for distinguishing high-grade (G3/4) from low-grade (G1/2) disease. The expression profile was further validated for performance and clinical use in 283 frozen renal cancer samples and 127 ex vivo renal mass biopsy samples, respectively. The area under curve (AUC) was used to quantify discriminative ability and was compared using the De-long test. Using the discovery dataset, we identified a 24-gene signature for high-grade disease with an AUC of 0.884. After applied to the development dataset, an eight-gene profile was defined and achieved an AUC of 0.823. Accuracy of eight-gene panel was maintained in the renal mass biopsies (RMB) samples (AUC = 0.821). In summary, using three-stage design, we validated an eight-gene expression signature for predicting high Fuhrman grade of ccRCC. This tool may help to reveal the characteristics of ccRCC biopsy specimens.
authors.affiliation: Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China.
authors.forename: Fangning
authors.initials: F
authors.lastname: Wan
authors.affiliation: Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China.
authors.forename: Chengtao
authors.initials: C
authors.lastname: Han
authors.affiliation: Canhelp Genomics Co. Ltd., Hangzhou, China.
authors.forename: Qinghua
authors.initials: Q
authors.lastname: Xu
authors.affiliation: Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China.
authors.forename: Junlong
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China.
authors.forename: Bo
authors.initials: B
authors.lastname: Dai
authors.affiliation: Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China.
authors.forename: Hailiang
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China.
authors.forename: Guohai
authors.initials: G
authors.lastname: Shi
authors.affiliation: Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China.
authors.forename: Weijie
authors.initials: W
authors.lastname: Gu
authors.affiliation: Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China.
authors.forename: Dingwei
authors.initials: D
authors.lastname: Ye
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019540:Area Under Curve; D001706:Biopsy; D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D015331:Cohort Studies; D005260:Female; D005629:Frozen Sections; D006801:Humans; D053208:Kaplan-Meier Estimate; D007680:Kidney Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics*; D009392:Nephrectomy; D011237:Predictive Value of Tests; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D012372:ROC Curve; D020133:Reverse Transcriptase Polymerase Chain Reaction; D059467:Transcriptome; D016896:Treatment Outcome
chemical_list: D009363:Neoplasm Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm
keywords: Fuhrman grade; TCGA; biomarker; clear cell renal cell carcinoma; renal mass biopsy