Estimation of tumor cell total mRNA expression in 15 cancer types predicts disease progression,Nature Biotechnology

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Estimation of tumor cell total mRNA expression in 15 cancer types predicts disease progression
Nature Biotechnology ( IF 46.9 ) Pub Date : 2022-06-13 , DOI: 10.1038/s41587-022-01342-x
Shaolong Cao ₁ , Jennifer R Wang ₂ , Shuangxi Ji ₁ , Peng Yang _{1,

3} , Yaoyi Dai _{1,

4} , Shuai Guo ₁ , Matthew D Montierth _{1,

4} , John Paul Shen ₅ , Xiao Zhao ₂ , Jingxiao Chen ₁ , Jaewon James Lee _{6,

7,

8} , Paola A Guerrero _{6,

7} , Nicholas Spetsieris ₉ , Nikolai Engedal ₁₀ , Sinja Taavitsainen ₁₁ , Kaixian Yu ₁₂ , Julie Livingstone _{13,

14,

15,

16} , Vinayak Bhandari ₁₇ , Shawna M Hubert ₁₈ , Najat C Daw ₁₉ , P Andrew Futreal ₂₀ , Eleni Efstathiou ₉ , Bora Lim ₂₁ , Andrea Viale ₂₀ , Jianjun Zhang ₁₈ , Matti Nykter ₁₁ , Bogdan A Czerniak ₂₂ , Powel H Brown ₂₃ , Charles Swanton ₂₄ , Pavlos Msaouel _{7,

9} , Anirban Maitra _{6,

7,

22} , Scott Kopetz ₅ , Peter Campbell ₂₅ , Terence P Speed _{26,

27} , Paul C Boutros _{13,

14,

15,

16,

17} , Hongtu Zhu ₁₂ , Alfonso Urbanucci ₁₀ , Jonas Demeulemeester _{28,

29} , Peter Van Loo _{28,

30} , Wenyi Wang _{1,

12}

Affiliation

Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Department of Statistics, Rice University, Houston, TX, USA.
Baylor College of Medicine, Houston, TX, USA.
Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Sheikh Ahmed Center for Pancreatic Cancer Research, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Department of Tumor Biology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway.
Faculty of Medicine and Health Technology, Tampere University and Tays Cancer Center, Tampere, Finland.
Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Department of Human Genetics, University of California, Los Angeles, Los Angeles, CA, USA.
Department of Urology, University of California, Los Angeles, Los Angeles, CA, USA.
Institute for Precision Health, University of California, Los Angeles, Los Angeles, CA, USA.
Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, CA, USA.
Department of Medical Biophysics, University of Toronto, Toronto ON, Canada.
Department of Thoracic Head Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Department of Pediatrics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
The Francis Crick Institute, London, UK.
Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, UK.
Bioinformatics Division, Walter and Eliza Hall Institute of Medical Research, Parkville, VC, Australia.
School of Mathematics and Statistics, The University of Melbourne, Melbourne, VC, Australia.
Cancer Genomics Laboratory, The Francis Crick Institute, London, UK.
Department of Human Genetics, KU Leuven, Leuven, Belgium.
Department of Genetics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Single-cell RNA sequencing studies have suggested that total mRNA content correlates with tumor phenotypes. Technical and analytical challenges, however, have so far impeded at-scale pan-cancer examination of total mRNA content. Here we present a method to quantify tumor-specific total mRNA expression (TmS) from bulk sequencing data, taking into account tumor transcript proportion, purity and ploidy, which are estimated through transcriptomic/genomic deconvolution. We estimate and validate TmS in 6,590 patient tumors across 15 cancer types, identifying significant inter-tumor variability. Across cancers, high TmS is associated with increased risk of disease progression and death. TmS is influenced by cancer-specific patterns of gene alteration and intra-tumor genetic heterogeneity as well as by pan-cancer trends in metabolic dysregulation. Taken together, our results indicate that measuring cell-type-specific total mRNA expression in tumor cells predicts tumor phenotypes and clinical outcomes.

中文翻译：

估算 15 种癌症类型中肿瘤细胞总 mRNA 表达可预测疾病进展

单细胞 RNA 测序研究表明，总 mRNA 含量与肿瘤表型相关。然而，迄今为止，技术和分析方面的挑战阻碍了对总 mRNA 含量的大规模泛癌检查。在这里，我们提出了一种从批量测序数据中量化肿瘤特异性总 mRNA 表达 (TmS) 的方法，同时考虑到通过转录组/基因组反卷积估计的肿瘤转录本比例、纯度和倍性。我们评估并验证了 15 种癌症类型的 6,590 名患者肿瘤的 TmS，识别了显着的肿瘤间变异。在所有癌症中，高 TmS 与疾病进展和死亡风险增加相关。TmS 受到癌症特异性基因改变模式和肿瘤内遗传异质性以及代谢失调的泛癌趋势的影响。

更新日期：2022-06-14

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