前列腺癌發(fā)病率在西方國家位于男性惡性腫瘤首位,，隨著我國社會人口老齡化，該病發(fā)病率近年來顯著上升,。前列腺癌有著明顯的種族特異性,，然而,，產(chǎn)生這種特異性的分子生物學機制至今未明。
第二軍醫(yī)大學長海醫(yī)院孫穎浩教授運用RNA-seq技術首次對中國人前列腺癌及癌旁組織進行系統(tǒng)研究,，發(fā)現(xiàn)新型融合基因,、癌相關長鏈非編碼RNA、異構體和點突變,。研究發(fā)現(xiàn),，在歐美人群中普遍高頻表達（50-80%）的融合基因TMPRSS2-ERG在中國人群中的表達率僅有20%左右，而在歐美人群中尚未發(fā)現(xiàn)的融合基因CTAGE5-KHDRBS3和USP9Y-TTTY15在中國人群中卻有很高的表達頻率,，分別為37%和35.2%,，提示這些融合基因具有中國人群特異性。相關論文發(fā)表在2月21日的《細胞研究》（Cell Research）雜志上,。
研究人員發(fā)現(xiàn)多個癌組織差異性表達的長鏈非編碼RNA進行了驗證,，發(fā)現(xiàn)PCA3，F(xiàn)R0348383 和 MALAT-1在癌組織中的過表達率分別為80%,，72.5%和82.5%,，F(xiàn)R0257520 在癌組織中的低表達率為82.5%。此外,，研究者還發(fā)現(xiàn)并驗證了PSA新型異構體,，具有潛在的診斷價值。
研究人員根據(jù)此次研究結果繪制了中國人群特異性的前列腺癌圖譜,，提出了3條關鍵信號通路,，為深入認識中國人群前列腺癌的發(fā)生發(fā)展機制奠定基礎。這些研究成果是第二代測序的成功范例,，首次揭示了中國人群前列腺癌的全貌,，新研究為進一步了解前列腺癌的診斷、發(fā)病演化機制和種族差異性提供了新線索,。（生物谷 bioon.com）
doi:10.1038/cr.2012.30
PMC:
PMID:
RNA-seq analysis of prostate cancer in the Chinese population identifies recurrent gene fusions, cancer-associated long noncoding RNAs and aberrant alternative splicings
Shancheng Ren, Zhiyu Peng, Jian-Hua Mao, Yongwei Yu, Changjun Yin, Xin Gao, Zilian Cui, Jibin Zhang, Kang Yi, Weidong Xu, Chao Chen, Fubo Wang, Xinwu Guo, Ji Lu, Jun Yang, Min Wei, Zhijian Tian, Yinghui Guan, Liang Tang, Chuanliang Xu, Linhui Wang, Xu Gao, Wei Tian, Jian Wang, Huanming Yang, Jun Wang and Yinghao Sun
There are remarkable disparities among patients of different races with prostate cancer; however, the mechanism underlying this difference remains unclear. Here, we present a comprehensive landscape of the transcriptome profiles of 14 primary prostate cancers and their paired normal counterparts from the Chinese population using RNA-seq, revealing tremendous diversity across prostate cancer transcriptomes with respect to gene fusions, long noncoding RNAs (long ncRNA), alternative splicing and somatic mutations. Three of the 14 tumors (21.4%) harbored a TMPRSS2-ERG fusion, and the low prevalence of this fusion in Chinese patients was further confirmed in an additional tumor set (10/54=18.5%). Notably, two novel gene fusions, CTAGE5-KHDRBS3 (20/54=37%) and USP9Y-TTTY15 (19/54=35.2%), occurred frequently in our patient cohort. Further systematic transcriptional profiling identified numerous long ncRNAs that were differentially expressed in the tumors. An analysis of the correlation between expression of long ncRNA and genes suggested that long ncRNAs may have functions beyond transcriptional regulation. This study yielded new insights into the pathogenesis of prostate cancer in the Chinese population.
