Identification and validation of an eight‐gene expression signature for predicting high Fuhrman grade renal cell carcinoma

• Published in: International journal of cancer 2017-03, Vol.140 (5), p.1199-1208
• Main Authors: Wan, Fangning, Zhu, Yao, Han, Chengtao, Xu, Qinghua, Wu, Junlong, Dai, Bo, Zhang, Hailiang, Shi, Guohai, Gu, Weijie, Ye, Dingwei
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Area Under Curve; biomarker; Biopsy; Cancer; Carcinoma, Renal Cell - genetics; Carcinoma, Renal Cell - mortality; Carcinoma, Renal Cell - pathology; Carcinoma, Renal Cell - surgery; clear cell renal cell carcinoma; Cohort Studies; Female; Frozen Sections; Fuhrman grade; Gene expression; Genomes; Humans; Kaplan-Meier Estimate; Kidney Neoplasms - genetics; Kidney Neoplasms - mortality; Kidney Neoplasms - pathology; Kidney Neoplasms - surgery; Male; Medical research; Middle Aged; Neoplasm Grading; Neoplasm Proteins - biosynthesis; Neoplasm Proteins - genetics; Nephrectomy; Predictive Value of Tests; renal mass biopsy; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - genetics; RNA, Neoplasm - genetics; ROC Curve; TCGA; Transcriptome; Treatment Outcome
• ISSN: 0020-7136; 1097-0215
• DOI: 10.1002/ijc.30535

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. What's new? Advanced clear cell renal cell carcinoma (ccRCC) is an aggressive and often fatal disease. Despite the existence of well‐established grading systems, challenges remain in ccRCC diagnosis, including the need to overcome grading inaccuracies during renal mass biopsy (RMB). Here, using data from the Cancer Genome Atlas, a predictive gene panel was developed to improve efforts to distinguish between high‐ and low‐grade ccRCC. An eight‐gene signature was validated clinically in RMB samples from ccRCC patients and was significantly more accurate in predicting high‐grade ccRCC than conventional approaches. The novel gene signature could facilitate risk‐stratification and therapeutic decision‐making in ccRCC.