伊匹单抗联合尼妥珠单抗一线治疗临床获益的转移性透明细胞肾细胞癌患者肿瘤的基因组和转录组特征

IF 1.1 Q4 ONCOLOGY
Kidney Cancer Pub Date : 2023-12-18 DOI:10.3233/kca-230011
N. Tripathi, L. Meza, N. Sayegh, Ameish Govindarajan, Sara A. Byron, Jiaming Zhang, B. Chigarira, Y. Jo, Z. Zengin, Haoran Li, G. Gebrael, A. Desai, N. Agarwal, U. Swami, B. Maughan, S. Pal
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引用次数: 0

摘要

背景:伊匹单抗加尼伐单抗被批准作为中危或低危转移性肾细胞癌(mRCC)的一线治疗方案。然而,35%的患者在接受伊匹单抗加尼夫单抗治疗的6个月内病情进展,而且没有有效的基因组生物标志物能预测疗效。在本研究中,我们探讨了透明细胞mRCC患者的基因组和转录组差异。治疗方法纳入IMDC风险评分中等或较差的透明细胞mRCC患者,这些患者在开始接受系统治疗前均已进行了肿瘤全外显子组测序(含/不含转录组测序)。开始治疗后至少 6 个月内出现完全应答、部分应答或病情稳定的患者被归入 "临床获益 "组,其余患者被归入 "无临床获益 "组。组间基因组改变频率采用卡方检验进行评估。差异表达基因和基因组分别通过 DeSeq2 和 GSEA v4.2.3 进行鉴定。结果:53 例透明细胞 mRCC 患者(37 例临床获益,16 例无临床获益)符合条件并纳入研究。两组患者的基因组改变频率无明显差异。14例患者(9例临床获益,5例无临床获益)获得了基线肿瘤转录组数据。临床获益组富含顶端表面和 KRAS 信号下调的通路,而无临床获益组富含炎症通路。结论这些研究结果表明,通过RNA测序评估的肿瘤特异性基因表达可作为伊匹单抗加尼伐单抗治疗反应的潜在生物标志物。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Genomic and Transcriptomic Characteristics of Tumors of Patients with Metastatic Clear Cell Renal Cell Carcinoma Clinically Benefiting from First-Line Treatment with Ipilimumab Plus Nivolumab
Background: Ipilimumab plus nivolumab is approved as a first-line treatment for intermediate or poor risk metastatic renal cell carcinoma (mRCC). However, ∼35% of patients progress within six months on ipilimumab plus nivolumab, and no validated genomic biomarkers predict the benefit. In this study, we explore the genomic and transcriptomic differences among patients with clear cell mRCC patients who either did or did not experience clinical benefit from first-line ipilimumab plus nivolumab therapy. Method: Patients with clear cell mRCC intermediate or poor IMDC risk scores, with available tumor whole exome with/without transcriptome sequencing before starting systemic therapy were included. Patients who developed a complete response, partial response, or stable disease for at least six months after initiating treatment were categorized into the ‘clinical benefit’ group, whereas the rest were classified as ‘no clinical benefit.’ Genomic alteration frequencies between the groups were assessed with a chi-square test. Differentially expressed genes and gene sets were identified via DeSeq2 and GSEA v4.2.3, respectively. Result: 53 patients with clear cell mRCC (37 clinical benefit and 16 no clinical benefit) were eligible and included. No significant difference was found in the genomic alteration frequencies between these groups. Baseline tumor transcriptomic data were available for 14 patients (9 clinical benefit and 5 no clinical benefit). The apical surface and pathways downregulated by KRAS signaling were enriched in the clinical benefit group, whereas inflammatory pathways were enriched in the no clinical benefit group. Conclusion: These findings suggest that tumor specific gene expression as assessed by RNA sequencing could serve as a potential biomarker of response to ipilimumab plus nivolumab therapy.
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来源期刊
Kidney Cancer
Kidney Cancer Multiple-
CiteScore
0.90
自引率
8.30%
发文量
23
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