Intratumor heterogeneity (ITH) is a biomarker of tumor progression, metastasis, and immune evasion. Previous studies evaluated ITH mostly based on DNA alterations. Here, we developed a new algorithm (DEPTH) for quantifying ITH based on mRNA alterations in the tumor. DEPTH scores displayed significant correlations with ITH-associated features (genomic instability, tumor advancement, unfavorable prognosis, immunosuppression, and drug response). Compared to DNA-based ITH scores (EXPANDS, PhyloWGS, MATH, and ABSOLUTE), DEPTH scores had stronger correlations with antitumor immune signatures, cell proliferation, stemness, tumor advancement, survival prognosis, and drug response. Compared to two other mRNA-based ITH scores (tITH and sITH), DEPTH scores showed stronger and more consistent associations with genomic instability, unfavorable tumor phenotypes and clinical features, and drug response. We further validated the reliability and robustness of DEPTH in 50 other datasets. In conclusion, DEPTH may provide new insights into tumor biology and potential clinical implications for cancer prognosis and treatment.

肿瘤内异质性（ITH）是肿瘤进展、转移和免疫逃避的生物标志物。以前的研究主要基于 DNA 改变评估 ITH。在这里，我们开发了一种新算法 (DEPTH)，用于根据肿瘤中 mRNA 的变化来量化 ITH。深度评分与 ITH 相关特征（基因组不稳定性、肿瘤进展、预后不良、免疫抑制和药物反应）显着相关。与基于 DNA 的 ITH 评分（EXPANDS、PhyloWGS、MATH 和 ABSOLUTE）相比，DEPTH 评分与抗肿瘤免疫特征、细胞增殖、干性、肿瘤进展、生存预后和药物反应具有更强的相关性。与其他两种基于 mRNA 的 ITH 评分（tITH 和 sITH）相比，DEPTH 评分显示出与基因组不稳定性更强且更一致的关联，不利的肿瘤表型和临床特征，以及药物反应。我们在其他 50 个数据集中进一步验证了 DEPTH 的可靠性和稳健性。总之，DEPTH 可能为肿瘤生物学和癌症预后和治疗的潜在临床意义提供新的见解。