PDF(Pubmed)
Abstract：
Pyrroline-5-carboxylate reductase (PYCR) is pivotal in converting pyrroline-5-carboxylate (P5C) to proline, the final step in proline synthesis. Three isoforms, PYCR1, PYCR2, and PYCR3, existed and played significant regulatory roles in tumor initiation and progression. In this study, we first assessed the molecular and immune characteristics of PYCRs by a pan-cancer analysis, especially focusing on their prognostic relevance. Then, a kidney renal clear cell carcinoma (KIRC)-specific prognostic model was established, incorporating pathomics features to enhance predictive capabilities. The biological functions and regulatory mechanisms of PYCR1 and PYCR2 were investigated by in vitro experiments in renal cancer cells. The PYCRs\' expressions were elevated in diverse tumors, correlating with unfavorable clinical outcomes. PYCRs were enriched in cancer signaling pathways, significantly correlating with immune cell infiltration, tumor mutation burden (TMB), and microsatellite instability (MSI). In KIRC, a prognostic model based on PYCR1 and PYCR2 was independently validated statistically. Leveraging features from H&E-stained images, a pathomics feature model reliably predicted patient prognosis. In vitro experiments demonstrated that PYCR1 and PYCR2 enhanced the proliferation and migration of renal carcinoma cells by activating the mTOR pathway, at least in part. This study underscores PYCRs\' pivotal role in various tumors, positioning them as potential prognostic biomarkers and therapeutic targets, particularly in malignancies like KIRC. The findings emphasize the need for a broader exploration of PYCRs\' implications in pan-cancer contexts.
摘要：
吡咯-5-羧酸还原酶（PYCR）在将吡咯-5-羧酸（P5C）转化为脯氨酸方面至关重要，脯氨酸合成的最后一步。三种亚型，PYCR1、PYCR2和PYCR3在肿瘤发生和发展过程中存在并发挥重要的调节作用。在这项研究中,我们首先通过泛癌症分析评估了PYCRs的分子和免疫特征，特别是关注它们的预后相关性。然后，建立了肾透明细胞癌（KIRC）特异性预后模型，整合pathomics功能以增强预测能力。通过肾癌细胞的体外实验研究了PYCR1和PYCR2的生物学功能和调控机制。PYCRs的表达在不同的肿瘤中升高，与不利的临床结果相关。PYCR在癌症信号通路中富集，与免疫细胞浸润显着相关，肿瘤突变负荷（TMB），和微卫星不稳定性（MSI）。在KIRC，基于PYCR1和PYCR2的预后模型在统计学上得到独立验证.利用H&E染色图像的功能，病理组学特征模型能够可靠地预测患者的预后.体外实验证明PYCR1和PYCR2通过激活mTOR通路增强肾癌细胞的增殖和迁移,至少部分。这项研究强调了PYCRs在各种肿瘤中的关键作用，将它们定位为潜在的预后生物标志物和治疗靶标，特别是像KIRC这样的恶性肿瘤。研究结果强调需要更广泛地探索PYCR在泛癌症环境中的意义。
