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Abstract：
Prostate cancer (PCa) is a complex and biologically diverse disease with no curative treatment options at present. This study aims to utilize computational methods to explore potential anti-PCa compounds based on differentially expressed genes (DEGs), with the goal of identifying novel therapeutic indications or repurposing existing drugs. The methods employed in this study include DEGs-to-drug prediction, pharmacokinetics prediction, target prediction, network analysis, and molecular docking. The findings revealed a total of 79 upregulated DEGs and 110 downregulated DEGs in PCa, which were used to identify drug compounds capable of reversing the dysregulated conditions (dexverapamil, emetine, parthenolide, dobutamine, terfenadine, pimozide, mefloquine, ellipticine, and trifluoperazine) at a threshold probability of 20% on several molecular targets, such as serotonin receptors 2a/2b/2c, HERG protein, adrenergic receptors alpha-1a/2a, dopamine D3 receptor, inducible nitric oxide synthase (iNOS), epidermal growth factor receptor erbB1 (EGFR), tyrosine-protein kinases, and C-C chemokine receptor type 5 (CCR5). Molecular docking analysis revealed that terfenadine binding to inducible nitric oxide synthase (-7.833 kcal.mol-1) and pimozide binding to HERG (-7.636 kcal.mol-1). Overall, binding energy ΔGbind (Total) at 0 ns was lower than that of 100 ns for both the Terfenadine-iNOS complex (-101.707 to -103.302 kcal.mol-1) and Ellipticine-TOPIIα complex (-42.229 to -58.780 kcal.mol-1). In conclusion, this study provides insight on molecular targets that could possibly contribute to the molecular mechanisms underlying PCa. Further preclinical and clinical studies are required to validate the therapeutic effectiveness of these identified drugs in PCa disease.
摘要：
前列腺癌（PCa）是一种复杂且生物学多样的疾病，目前尚无治愈性治疗选择。本研究旨在利用计算方法探索基于差异表达基因(DEGs)的潜在抗PCa化合物,目的是确定新的治疗适应症或重新利用现有药物。本研究采用的方法包括DEGs对药物的预测，药代动力学预测，目标预测，网络分析,和分子对接。研究结果表明，PCa中共有79个上调的DEG和110个下调的DEG，用于鉴定能够逆转失调病症的药物化合物(右旋维拉帕米，依米汀,小白菊内酯,多巴酚丁胺,特非那定,匹莫齐特,甲氟喹,椭圆,和三氟拉嗪)在几个分子靶标上的阈值概率为20%，如血清素受体2a/2b/2c，HERG蛋白,肾上腺素能受体α-1a/2a，多巴胺D3受体，诱导型一氧化氮合酶（iNOS），表皮生长因子受体erbB1（EGFR），酪氨酸蛋白激酶，和C-C趋化因子受体5型（CCR5）。分子对接分析显示，特非那定与诱导型一氧化氮合酶（-7.833kcal。mol-1）和匹莫齐特结合HERG（-7.636kcal。mol-1)。总的来说,特非那定-iNOS复合物在0ns时的结合能ΔG结合（总计）均低于100ns（-101.707至-103.302kcal。mol-1）和埃利汀-TOPIIα复合物（-42.229至-58.780kcal。mol-1)。总之,这项研究提供了对可能有助于PCa潜在分子机制的分子靶标的见解.需要进一步的临床前和临床研究来验证这些鉴定的药物在PCa疾病中的治疗效果。
