Samaržija Ivana, Trošelj Koraljka Gall, Konjevoda Paško
Laboratory for Epigenomics, Division of Molecular Medicine, Ruđer Bošković Institute, 10000 Zagreb, Croatia.
Cancers (Basel). 2023 Feb 18;15(4):1309. doi: 10.3390/cancers15041309.
Prostate cancer is among the leading cancers according to both incidence and mortality. Due to the high molecular, morphological and clinical heterogeneity, the course of prostate cancer ranges from slow growth that usually does not require immediate therapeutic intervention to aggressive and fatal disease that spreads quickly. However, currently available biomarkers cannot precisely predict the course of a disease, and novel strategies are needed to guide prostate cancer management. Amino acids serve numerous roles in cancers, among which are energy production, building block reservoirs, maintenance of redox homeostasis, epigenetic regulation, immune system modulation and resistance to therapy. In this article, by using The Cancer Genome Atlas (TCGA) data, we found that the expression of amino acid metabolism-related genes is highly aberrant in prostate cancer, which holds potential to be exploited in biomarker design or in treatment strategies. This change in expression is especially evident for catabolism genes and transporters from the solute carrier family. Furthermore, by using recursive partitioning, we confirmed that the Gleason score is strongly prognostic for progression-free survival. However, the expression of the genes (phosphatidylserine and sphingolipids generation) and (hypotaurine generation) can refine prognosis for high and low Gleason scores, respectively. Therefore, our results hold potential for novel prostate cancer progression biomarkers.
无论在发病率还是死亡率方面，前列腺癌都是主要癌症之一。由于其在分子、形态和临床方面存在高度异质性，前列腺癌的病程差异很大，从通常无需立即进行治疗干预的缓慢生长，到迅速扩散的侵袭性致命疾病。然而，目前可用的生物标志物无法精确预测疾病进程，因此需要新的策略来指导前列腺癌的管理。氨基酸在癌症中发挥着多种作用，包括能量产生、构建物质储备、维持氧化还原稳态、表观遗传调控、免疫系统调节以及对治疗的抗性。在本文中，通过使用癌症基因组图谱（TCGA）数据，我们发现氨基酸代谢相关基因的表达在前列腺癌中高度异常，这在生物标志物设计或治疗策略中具有潜在的应用价值。这种表达变化在分解代谢基因和溶质载体家族的转运蛋白中尤为明显。此外，通过递归划分，我们证实Gleason评分对无进展生存期具有很强的预后价值。然而，基因（磷脂酰丝氨酸和鞘脂生成）和（次牛磺酸生成）的表达分别可以细化高、低Gleason评分的预后。因此，我们的研究结果为新型前列腺癌进展生物标志物提供了潜力。
