一种新型多基因检测板（Sig27）通过与免疫抑制特征的高度关联有力地预测肾细胞癌的不良预后。
A novel multigene panel (Sig27) robustly predicts poor prognosis of renal cell carcinoma via high-level associations with immunosuppressive features.
作者信息
Dong Ying, Shayegan Bobby, Su Yingying, Neira Sandra Vega, Tang Damu
机构信息
Urological Cancer Center for Research and Innovation (UCCRI), St Joseph's Hospital, Hamilton, ON, L8N 4A6, Canada.
Department of Surgery, McMaster University, Hamilton, ON, L8S 4K1, Canada.
出版信息
BJC Rep. 2025 Mar 17;3(1):16. doi: 10.1038/s44276-025-00128-3.
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.
背景
我们研究了一个源自前列腺癌的27基因panel（Sig27），用于肾细胞癌（透明细胞肾细胞癌/ccRCC、乳头状肾细胞癌/pRCC和嫌色性肾细胞癌/chRCC）的风险分层。
方法
检测了960例肾细胞癌和201例肾组织中Sig27基因的表达。评估Sig27在肾细胞癌中预测总生存期（OS）、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）的相关性。
结果
Sig27能可靠地预测ccRCC、pRCC和chRCC的OS。Sig27对高风险ccRCC进行分层：中位生存月数（MSM）为19.3，死亡占80.4%；高风险pRCC（MSM为19.6，死亡占58.6%），而低风险ccRCC（死亡占2.9%）和pRCC（死亡占2.7%）。Sig27包含几个与肾细胞癌免疫抑制特征相关的新基因。FPR3、NOD2、MCTP1、LAMP3、TFEC和FAM65B与肾细胞癌中的MDSC、Treg、TAM和多种（≥12种）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引发促炎反应；它们的上调可能导致肾细胞癌中的慢性炎症。Sig27元基因在ccRCC相关免疫细胞中表达：耗竭的CD8T细胞、TAM、Treg等。
结论
Sig27是一种新型有效的泛肾细胞癌生物标志物，与肾细胞癌免疫抑制特征高度相关。
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