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转移性透明细胞肾细胞癌接受免疫治疗患者中铜死亡相关长链非编码RNA的上调表明疾病进展。

Up-regulation of Cuproptosis-related lncRNAS in Patients Receiving Immunotherapy for Metastatic Clear Cell Renal Cell Carcinoma Indicates Progressive Disease.

作者信息

Katifelis Hector, Grammatikaki Stamatiki, Zakopoulou Roubini, Bamias Aristotelis, Karamouzis Michalis V, Stravodimos Konstantinos, Gazouli Maria

机构信息

Department of Basic Medical Sciences, Laboratory of Biology, Medical School, National and Kapodistrian University of Athens, Athens, Greece.

2 Propaedeutic Department of Internal Medicine, Attikon University Hospital, National and Kapodistrian University of Athens, School of Medicine, Athens, Greece.

出版信息

In Vivo. 2025 Jan-Feb;39(1):146-151. doi: 10.21873/invivo.13812.

Abstract

BACKGROUND/AIM: Clear cell renal cell carcinoma (ccRCC) represents the most common type of renal cancer. When resectable, nephrectomy is the only radical treatment for ccRCC, however metastasis is already present at 30% of the patient population. Although great progress has been made in the field of targeted therapy with the emergence of immune checkpoint inhibitors (ICIs) the cure of metastatic ccRCC (mccRCC) remains far from achieved. Additionally, the need of biomarkers capable of predicting their therapeutic efficacy with the aim to ameliorate patient treatment and management is crucial. This study aimed to investigate potential changes in the expression of 3 cuproptosis-related lncRNAs, FOXD2-AS1, MINCR, LINC02154, in the blood of mccRCC patients that receive ICI-based treatments and whether these changes could be used to distinguish patients with clinical benefit (CB) from patients with progressive disease (PD).

MATERIALS AND METHODS

Peripheral blood from 31 mccRCC patients was obtained, prior to administration of ICI-immunotherapy. Using the RECIST criteria patients were subdivided into CB and PD groups. The fold change of FOXD2-AS1, MINCR, LINC02154 was evaluated using qRT-PCR.

RESULTS

The tested lncRNAs showed an increase in peripheral blood with the most notable up-regulation in FOXD2-AS1 and LINC02154 (fold change of 3.7 and 3.8 respectively), followed by MINCR, (fold change of 2.6) in the PD patient group.

CONCLUSION

Cuproptosis-related lncRNAs FOXD2-AS1, MINCR, LINC02154 show promise for the prediction of patient response (CB vs. PD) in ICI-based therapeutic schemes in patients with mccRCC.

摘要

背景/目的:透明细胞肾细胞癌(ccRCC)是最常见的肾癌类型。当可切除时,肾切除术是ccRCC的唯一根治性治疗方法,但30%的患者人群中已出现转移。尽管随着免疫检查点抑制剂(ICI)的出现,靶向治疗领域取得了巨大进展,但转移性ccRCC(mccRCC)的治愈仍远未实现。此外,迫切需要能够预测其治疗效果的生物标志物,以改善患者的治疗和管理。本研究旨在调查接受基于ICI治疗的mccRCC患者血液中3种铜死亡相关lncRNA(FOXD2-AS1、MINCR、LINC02154)表达的潜在变化,以及这些变化是否可用于区分具有临床获益(CB)的患者和疾病进展(PD)的患者。

材料与方法

在给予ICI免疫治疗之前,采集31例mccRCC患者的外周血。根据RECIST标准将患者分为CB组和PD组。使用qRT-PCR评估FOXD2-AS1、MINCR、LINC02154的倍数变化。

结果

在PD患者组中,检测的lncRNA在外周血中呈增加趋势,其中FOXD2-AS1和LINC02154上调最为显著(倍数变化分别为3.7和3.8),其次是MINCR(倍数变化为2.6)。

结论

铜死亡相关lncRNA FOXD2-AS1、MINCR、LINC02154有望预测mccRCC患者基于ICI治疗方案的患者反应(CB与PD)。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a962/11705156/c881519d47f7/in_vivo-39-148-g0001.jpg

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