解讀PYCR家族對ccRCC和泛癌細胞功能、預后價值、免疫浸潤的影響

2024年7月，福建醫科大學基礎醫學院,福建師范大學計算機與網絡安全學院(1 School of Basic Medical Sciences, Fujian Medical University,2 College of Computer and Cyber Security, Fujian Normal University,)Mingfang Zhang and Yuanlin Qi 在《International Journal of Molecular Sciences》上發表論文：“Deciphering the Effects of the PYCR Family on Cell Function, Prognostic Value, Immune Infiltration in ccRCC and Pan-Cancer”

“解讀PYCR家族對ccRCC和泛癌細胞功能、預后價值、免疫浸潤的影響”

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-羧酸還原酶(PYCR)是將吡咯-5-羧酸酯(P5C)轉化為脯氨酸的關鍵，這是脯氨酸合成的最后一步。PYCR1、PYCR2和PYCR3三種異構體存在，并在腫瘤的發生和發展中發揮著重要的調節作用。

在這項研究中，科研人員先通過泛癌癥分析評估了PYCRs的分子和免疫特征，特別是關注它們與預后的相關性。然后，建立腎透明細胞癌(KIRC)特異性預后模型，結合病理特征來增強預測能力。通過體外實驗研究PYCR1和PYCR2在腎癌細胞中的生物學功能和調控機制。PYCRs在多種腫瘤中的表達均升高，與不良臨床結果相關。PYCRs在腫瘤信號通路中富集，與免疫細胞浸潤、腫瘤突變負荷(TMB)和微衛星不穩定性(MSI)顯著相關。在KIRC中，基于PYCR1和PYCR2的預后模型在統計學上得到了獨立驗證。利用HE染色圖像的特征，病理特征模型可靠地預測患者預后。體外實驗表明，PYCR1和PYCR2通過激活mTOR通路，至少部分地增強了腎癌細胞的增殖和遷移。這項研究強調了PYCRs在各種腫瘤中的關鍵作用，將其定位為潛在的預后生物標志物和治療靶點，特別是在惡性腫瘤如KIRC中。這些發現強調需要更廣泛地探索PYCRs在泛癌癥背景下的意義。

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