Aguzzi Cristina, De Summa Simona, Molina-Cerrillo Javier, Alonso-Gordoa Teresa, Nabissi Massimo, Rizzo Mimma, Zeppellini Annalisa, Sunela Kaisa, Sorgentoni Giulia, Ortega Cinzia, Massari Francesco, Marques Monteiro Fernando Sabino, Battelli Nicola, Porta Camillo, Santoni Giorgio, Santoni Matteo
School of Pharmacy, University of Camerino, Camerino, Macerata, Italy.
Unità di Diagnostica Molecolare e Farmacogenetica, IRCCS Istituto Tumori Giovanni Paolo II Bari, Bari, Italy.
Biochem Biophys Rep. 2025 Aug 7;43:102162. doi: 10.1016/j.bbrep.2025.102162. eCollection 2025 Sep.
Renal Cell Carcinoma (RCC) represents a spectrum of tumors, characterized by heterogeneous growth patterns, histology and response to immune-based combinations.
The aim of the present retrospective analysis was to investigate the mRNA expression of 32 genes associated with RCC carcinogenesis and their potential involvement in patients treated with first-line immune-based combination therapies. Additionally, we examined the role of tumor heterogeneity by comparing mRNA expression levels between primary renal tumors and metastatic sites in a group of patients included in the ARON-1 study.
The study included patients with advanced RCC treated with first-line immune-based therapies. Total RNA was extracted from fixed paraffin-embedded tissue slices using the RNeasy FFPE Mini Kit. Quantitative RT-PCR was performed using the IQ5 Multicolor real-time PCR detection system. Coefficient of variations were calculated for each gene and compared between primary and metastatic samples.
17 patients were included in this analysis; 9 of them had both primary and metastatic samples available. Three of the 4 patients showing the highest mRNA expression levels of the 32 analyzed genes reported complete remissions, while 2 of the 3 patients with the lowest expression levels were primary refractory to first-line therapy. As for tumor heterogeneity, was the only gene significantly deregulated in the paired comparison.
We showed differences in mRNA expression between primary and metastatic sites, and proposed a possible link to the response to first-line immune combination therapies. Additional research is required to clarify their potential as prognostic or predictive biomarkers.
肾细胞癌（RCC）是一系列肿瘤，其特征在于生长模式、组织学以及对基于免疫的联合治疗的反应具有异质性。
本回顾性分析的目的是研究与RCC致癌作用相关的32个基因的mRNA表达及其在接受一线基于免疫的联合治疗的患者中的潜在作用。此外，我们通过比较ARON-1研究中一组患者的原发性肾肿瘤和转移部位之间的mRNA表达水平，研究了肿瘤异质性的作用。
该研究纳入了接受一线基于免疫治疗的晚期RCC患者。使用RNeasy FFPE Mini试剂盒从固定石蜡包埋组织切片中提取总RNA。使用IQ5多色实时PCR检测系统进行定量RT-PCR。计算每个基因的变异系数，并在原发性和转移性样本之间进行比较。
本分析纳入了17名患者；其中9名患者同时有原发性和转移性样本。在分析的32个基因中，mRNA表达水平最高的4名患者中有3名报告完全缓解，而表达水平最低的3名患者中有2名对一线治疗原发性难治。至于肿瘤异质性，在配对比较中，是唯一显著失调的基因。
我们显示了原发性和转移部位之间mRNA表达的差异，并提出了与一线免疫联合治疗反应的可能联系。需要进一步研究以阐明它们作为预后或预测生物标志物的潜力。
