15种癌症类型中肿瘤细胞总mRNA表达可预测疾病进展，这一成果由美国德克萨斯大学MD安德森癌症中心Wenyi Wang小组经过不懈努力而取得。2022年6月13日，国际学术期刊《自然-生物技术》发表了这一成果。

研究人员研发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，并考虑了通过转录组/基因组去卷积估计肿瘤转录的比例、纯度和倍性。研究评估并验证了15种癌症类型共6,590名患者肿瘤中的TmS，确定了显著的肿瘤间变异性。在各种癌症中，高TmS与疾病进展和死亡风险增加有关。TmS受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。

总之，该结果表明，测量肿瘤细胞中细胞类型特异性的总mRNA表达可预测肿瘤表型和临床结果。

据悉，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，技术和分析方法的缺陷阻碍了对大规模泛癌样本的总mRNA含量检查。

附：英文原文

Title: Estimation of tumor cell total mRNA expression in 15 cancer types predicts disease progression

Author: Cao, Shaolong, Wang, Jennifer R., Ji, Shuangxi, Yang, Peng, Dai, Yaoyi, Guo, Shuai, Montierth, Matthew D., Shen, John Paul, Zhao, Xiao, Chen, Jingxiao, Lee, Jaewon James, Guerrero, Paola A., Spetsieris, Nicholas, Engedal, Nikolai, Taavitsainen, Sinja, Yu, Kaixian, Livingstone, Julie, Bhandari, Vinayak, Hubert, Shawna M., Daw, Najat C., Futreal, P. Andrew, Efstathiou, Eleni, Lim, Bora, Viale, Andrea, Zhang, Jianjun, Nykter, Matti, Czerniak, Bogdan A., Brown, Powel H., Swanton, Charles, Msaouel, Pavlos, Maitra, Anirban, Kopetz, Scott, Campbell, Peter, Speed, Terence P., Boutros, Paul C., Zhu, Hongtu, Urbanucci, Alfonso, Demeulemeester, Jonas, Van Loo, Peter, Wang, Wenyi

Issue&Volume: 2022-06-13

Abstract: 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. Total mRNA expression in cancer cells is a marker for disease progression and death.

DOI: 10.1038/s41587-022-01342-x

Source: https://www.nature.com/articles/s41587-022-01342-x