Transcriptomic characterization and innovative molecular classification of clear cell renal cell carcinoma in the Chines
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PRIMARY RESEARCH
Cancer Cell International Open Access
Transcriptomic characterization and innovative molecular classification of clear cell renal cell carcinoma in the Chinese population Qiang Zhao1†, Jia Xue2†, Baoan Hong1† , Wubin Qian2, Tiezhu Liu3, Bin Fan4, Jie Cai4, Yongpeng Ji1, Jia Liu1, Yong Yang1, Qixiang Li5,6, Sheng Guo2* and Ning Zhang1*
Abstract Background: Large-scale initiatives like The Cancer Genome Atlas (TCGA) performed genomics studies on predominantly Caucasian kidney cancer. In this study, we aimed to investigate genomics of Chinese clear cell renal cell carcinoma (ccRCC). Methods: We performed whole-transcriptomic sequencing on 55 tumor tissues and 11 matched normal tissues from Chinese ccRCC patients. We systematically analyzed the data from our cohort and comprehensively compared with the TCGA ccRCC cohort. Results: It found that PBRM1 mutates with a frequency of 11% in our cohort, much lower than that in TCGA Caucasians (33%). Besides, 31 gene fusions including 5 recurrent ones, that associated with apoptosis, tumor suppression and metastasis were identified. We classified our cohort into three classes by gene expression. Class 1 shows significantly elevated gene expression in the VEGF pathway, while Class 3 has comparably suppressed expression of this pathway. Class 2 is characterized by increased expression of extracellular matrix organization genes and is associated with high-grade tumors. Applying the classification to TCGA ccRCC patients revealed better distinction of tumor prognosis than reported classifications. Class 2 shows worst survival and Class 3 is a rare subtype ccRCC in the TCGA cohort. Furthermore, computational analysis on the immune microenvironment of ccRCC identified immune-active and tolerant tumors with significant increased macrophages and depleted CD4 positive T-cells, thus some patients may benefit from immunotherapies. Conclusion: In summary, results presented in this study shed light into distinct genomic expression profiles in Chinese population, modified the stratification patterns by new molecular classification, and gave practical guidelines on clinical treatment of ccRCC patients. Keywords: Transcriptomic characterization, Molecular classification, Clear cell renal cell carcinoma, TCGA, Immunophenotyping *Correspondence: [email protected]; [email protected] † Qiang Zhao, Jia Xue and Baoan Hong contributed equally to this work 1 Key laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Urology, Peking University Cancer Hospital & Institute, 52 Fucheng Road, Haidian District, Beijing 100142, People’s Republic of China 2 Systems Biology, Crown Bioscience Inc., No. 218 Xinghu Street, Suzhou Industrial Park, Suzhou 215028, People’s Republic of China Full list of author information is available at the end of the article
Background Kidney cancer, or renal cell carcinoma (RCC), accounts for about 2–3% of tumor malignancy in adults, and is one of the most lethal urological cancers [1]. Clear cell renal
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