Cancer cells are known to undergo metabolic adaptation to cater to their enhanced energy demand. Nicotinamide adenine dinucleotide (NAD) is an essential metabolite regulating many cellular processes within the cell. The enzymes required for NAD synthesis, starting from the base precursor - tryptophan, are expressed in the liver and the kidney, while all other tissues convert NAD from intermediate precursors. The liver, being an active metabolic organ, is a primary contributor to NAD biosynthesis. Inhibition of key enzymes in the NAD biosynthetic pathways is proposed as a strategy for designing anti-cancer drugs. On the other hand, NAD supplementation has also been reported to be beneficial in cancer in some cases. As metabolic adaptation that occurs in cancer cells can lead to perturbations to the pathways, it is important to understand the exact nature of the perturbation in each individual patient. To investigate this, we use a mathematical modelling approach integrated with transcriptomes of patient samples from the TCGA-LIHC cohort. Quantitative profiling of the NAD biosynthesis pathway helps us understand the NAD biosynthetic status and changes in the controlling steps of the pathway. Our results indicate that NAD biosynthesis is heterogeneous among liver cancer patients, and that Nicotinate phosphoribosyl transferase (NAPRT) levels are indicative of the NAD biosynthetic status. Further, we find that reduced NAPRT levels combined with reduced Nicotinamide phosphoribosyl transferase (NAMPT) levels contribute to poor prognosis. Identification of the precise subgroup who may benefit from NAD supplementation in subgroup with low levels of NAPRT and NAMPT could be explored to improve patient outcome.

众所周知，癌细胞会进行代谢适应以满足其增强的能量需求。烟酰胺腺嘌呤二核苷酸 (NAD) 是调节细胞内许多细胞过程的必需代谢物。NAD 合成所需的酶，从碱基前体 - 色氨酸开始，在肝脏和肾脏中表达，而所有其他组织从中间前体转化 NAD。肝脏是一个活跃的代谢器官，是 NAD 生物合成的主要贡献者。提出了抑制 NAD 生物合成途径中的关键酶作为设计抗癌药物的策略。另一方面，据报道，在某些情况下，补充 NAD 对癌症有益。由于癌细胞中发生的代谢适应会导致对通路的干扰，了解每个患者的扰动的确切性质很重要。为了研究这一点，我们使用了一种数学建模方法，该方法与来自 TCGA-LIHC 队列的患者样本的转录组相结合。NAD 生物合成途径的定量分析有助于我们了解 NAD 生物合成状态和途径控制步骤的变化。我们的结果表明，肝癌患者的 NAD 生物合成是异质的，烟酸磷酸核糖基转移酶 (NAPRT) 水平表明 NAD 生物合成状态。此外，我们发现降低的 NAPRT 水平与降低的烟酰胺磷酸核糖基转移酶 (NAMPT) 水平相结合会导致预后不良。