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溶酶体依赖性细胞死亡在肾透明细胞癌中的分子特征及预后意义。

Molecular characteristics and prognostic significances of lysosomal-dependent cell death in kidney renal clear cell carcinoma.

机构信息

Department of Urology, First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, China.

Department of Dermatology, First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, China.

出版信息

Aging (Albany NY). 2024 Mar 7;16(5):4862-4888. doi: 10.18632/aging.205639.

DOI:10.18632/aging.205639
PMID:38460947
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10968703/
Abstract

Lysosomal-dependent cell death (LDCD) has an excellent therapeutic effect on apoptosis-resistant and drug-resistant tumors; however, the important role of LDCD-related genes (LDCD-RGs) in kidney renal clear cell carcinoma (KIRC) has not been reported. Initially, single-cell atlas of LDCD signal in KIRC was comprehensively depicted. We also emphasized the molecular characteristics of LDCD-RGs in various human neoplasms. Predicated upon the expressive quotients of LDCD-RGs, we stratified KIRC patients into tripartite cohorts denoted as C1, C2, and C3. Those allocated to the ambit of C1 evinced the most sanguine prognosis within the KIRC cohort, underscored by the acme of LDCD-RGs scores. This further confirms the significant role that LDCD-RGs play in both the pathophysiological foundation and clinical implications of KIRC. In culmination, by virtue of employing the LASSO-Cox analytical modality, we have ushered in an innovative and avant-garde prognostic framework tailored for KIRC, predicated on the bedrock of LDCD-RGs. The assemblage of KIRC instances was arbitrarily apportioned into constituents inclusive of a didactic cohort, an internally wielded validation cadre, and an externally administered validation cohort. Concurrently, patients were dichotomized into strata connoting elevated jeopardy synonymous with adverse prognostic trajectories, and conversely, diminished risk tantamount to favorable prognoses, contingent on the calibrated expressions of LDCD-RGs. Succinctly, our investigative findings serve to underscore the cardinal capacity harbored by LDCD-RGs within the KIRC milieu, concurrently birthing a pioneering prognostic schema intrinsically linked to the trajectory of KIRC and its attendant prognoses.

摘要

溶酶体依赖性细胞死亡 (LDCD) 对凋亡抵抗和耐药肿瘤具有极好的治疗效果;然而,LDCD 相关基因 (LDCD-RGs) 在肾透明细胞癌 (KIRC) 中的重要作用尚未报道。本研究首先全面描绘了 KIRC 中 LDCD 信号的单细胞图谱。我们还强调了 LDCD-RGs 在各种人类肿瘤中的分子特征。根据 LDCD-RGs 的表达系数,我们将 KIRC 患者分为三个亚组,分别表示为 C1、C2 和 C3。在 KIRC 队列中,被分配到 C1 范围内的患者表现出最乐观的预后,LDCD-RGs 评分达到峰值。这进一步证实了 LDCD-RGs 在 KIRC 的病理生理基础和临床意义中的重要作用。最后,通过使用 LASSO-Cox 分析模型,我们基于 LDCD-RGs 为 KIRC 引入了一种创新的、前卫的预后框架。将 KIRC 实例集任意分配到包括教学队列、内部验证框架和外部验证队列的组成部分中。同时,根据 LDCD-RGs 的表达情况,将患者分为表示预后不良的高风险分层和预后良好的低风险分层。总之,我们的研究结果强调了 LDCD-RGs 在 KIRC 环境中的核心作用,同时产生了与 KIRC 轨迹及其预后相关的开创性预后方案。

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