Pan-cancer analysis of non-coding transcripts reveals the prognostic onco-lncRNA HOXA10-AS in gliomas

Cell Reports

Jinsong Wu¹  Daniel Schramek¹  Samer M.I. Hussein²  Lingyan Jiang²  Valérie Watters³  Victoire Fort⁴  Ricky Tsai⁵  Peter B. Dirks⁶  Jie Zhang⁶  Christian A. Lee⁷  Shuai Wu⁸  Jüri Reimand⁸  Keren Isaev⁹  Fiona J. Coutinho⁹ 

[1] CHU of Québec-Université Laval Research Center, Oncology Division, Quebec City, QC, Canada;Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada;Neurosurgical Institute of Fudan University, Shanghai, China;Shanghai Clinical Medical Center of Neurosurgery, Shanghai, China;Shanghai Key Laboratory of Brain Function and Restoration and Neural Regeneration, Shanghai, China;Cancer Research Center, Université Laval, Quebec City, QC, Canada;Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China;Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada;Ontario Institute for Cancer Research, Toronto, ON, Canada;

关键词: long non-coding RNAs;    lncRNAs;    cancer;    prognostic biomarkers;    machine learning;    glioma;   

DOI  :  

来源: DOAJ

【 摘 要 】

Summary: Long non-coding RNAs (lncRNAs) are increasingly recognized as functional units in cancer and powerful biomarkers; however, most remain uncharacterized. Here, we analyze 5,592 prognostic lncRNAs in 9,446 cancers of 30 types using machine learning. We identify 166 lncRNAs whose expression correlates with survival and improves the accuracy of common clinical variables, molecular features, and cancer subtypes. Prognostic lncRNAs are often characterized by switch-like expression patterns. In low-grade gliomas, HOXA10-AS activation is a robust marker of poor prognosis that complements IDH1/2 mutations, as validated in another retrospective cohort, and correlates with developmental pathways in tumor transcriptomes. Loss- and gain-of-function studies in patient-derived glioma cells, organoids, and xenograft models identify HOXA10-AS as a potent onco-lncRNA that regulates cell proliferation, contact inhibition, invasion, Hippo signaling, and mitotic and neuro-developmental pathways. Our study underscores the pan-cancer potential of the non-coding transcriptome for identifying biomarkers and regulators of cancer progression.

【 授权许可】

Unknown