A novel multigene panel (Sig27) robustly predicts poor prognosis of renal cell carcinoma via high-level associations with immunosuppressive features.

BJC reports Pub Date : 2025-03-17 DOI:10.1038/s44276-025-00128-3

Ying Dong, Bobby Shayegan, Yingying Su, Sandra Vega Neira, Damu Tang

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Abstract

Background: We investigated a 27-gene panel (Sig27), derived from prostate cancer, for risk stratification of RCC (clear cell RCC/ccRCC, papillary RCC/pRCC, and chromophobe RCC/chRCC).

Methods: Sig27 gene expressions were examined in 960 RCC and 201 kidney tissues. Sig27 was evaluated for predicting overall survival (OS), association with immune checkpoints (IC), regulatory T cells (Tregs), myeloid-derived suppressor cells (MDSC), and tumor-associated macrophages (TAM) in RCC.

Results: Sig27 robustly predicts OS of ccRCC, pRCC, and chRCC. Sig27 stratifies high-risk ccRCCs: median survival month (MSM) 19.3 and 80.4% of deaths and high-risk pRCCs (MSM 19.6 and 58.6% of death) compared to low-risk ccRCCs (2.9% of death) and pRCCs (2.7% of fatality). Sig27 contains several novel genes related to the RCC immunosuppressive features. FPR3, NOD2, MCTP1, LAMP3, TFEC, and FAM65B are highly correlated with MDSC, Treg, TAM and multiple (≥12) ICs in RCCs. FPR3 and NOD2 are pattern recognition receptors and initiate proinflammatory responses via sensing pathogen-associated molecular patterns and damage-associated molecular patterns; their upregulations may contribute to chronic inflammation in RCC. The Sig27 metagene is expressed in ccRCC-associated immune cells: exhausted CD8T cells, TAM, Treg, and others.

Conclusions: Sig27 is a novel and effective pan-RCC biomarker with high-level associations with RCC immunosuppressive features.

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一种新的多基因面板（Sig27）通过与免疫抑制特征的高水平关联，强有力地预测肾细胞癌的不良预后。

背景：我们研究了从前列腺癌中提取的用于RCC（透明细胞RCC/ccRCC、乳头状RCC/pRCC和嗜铬RCC/chRCC）风险分层的27个基因面板（Sig27）：方法：研究了960例RCC和201例肾脏组织中Sig27基因的表达。方法：对960例RCC和201例肾脏组织中的Sig27基因表达进行了检测，评估了Sig27对RCC总生存率（OS）的预测作用，以及与免疫检查点（IC）、调节性T细胞（Tregs）、髓源性抑制细胞（MDSC）和肿瘤相关巨噬细胞（TAM）的关联：结果：Sig27能有效预测ccRCC、pRCC和chRCC的OS。与低风险ccRCC（2.9%死亡）和pRCC（2.7%死亡）相比，Sig27可对高风险ccRCC进行分层：中位生存月（MSM）为19.3，80.4%死亡；高风险pRCC（MSM为19.6，58.6%死亡）。Sig27 包含几个与 RCC 免疫抑制特征相关的新基因。FPR3、NOD2、MCTP1、LAMP3、TFEC和FAM65B与RCC中的MDSC、Treg、TAM和多个（≥12个）IC高度相关。FPR3和NOD2是模式识别受体，通过感知病原体相关分子模式和损伤相关分子模式启动促炎症反应；它们的上调可能会导致RCC的慢性炎症。Sig27元基因在ccRCC相关免疫细胞中表达：衰竭的CD8T细胞、TAM、Treg等：结论：Sig27是一种新型、有效的泛RCC生物标记物，与RCC免疫抑制特征高度相关。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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BJC reports

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