Ying Dong, Bobby Shayegan, Yingying Su, Sandra Vega Neira, Damu Tang
{"title":"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。","authors":"Ying Dong, Bobby Shayegan, Yingying Su, Sandra Vega Neira, Damu Tang","doi":"10.1038/s44276-025-00128-3","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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).</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>Sig27 is a novel and effective pan-RCC biomarker with high-level associations with RCC immunosuppressive features.</p>","PeriodicalId":519964,"journal":{"name":"BJC reports","volume":"3 1","pages":"16"},"PeriodicalIF":0.0000,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11914224/pdf/","citationCount":"0","resultStr":"{\"title\":\"A novel multigene panel (Sig27) robustly predicts poor prognosis of renal cell carcinoma via high-level associations with immunosuppressive features.\",\"authors\":\"Ying Dong, Bobby Shayegan, Yingying Su, Sandra Vega Neira, Damu Tang\",\"doi\":\"10.1038/s44276-025-00128-3\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>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).</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>Sig27 is a novel and effective pan-RCC biomarker with high-level associations with RCC immunosuppressive features.</p>\",\"PeriodicalId\":519964,\"journal\":{\"name\":\"BJC reports\",\"volume\":\"3 1\",\"pages\":\"16\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2025-03-17\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11914224/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"BJC reports\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1038/s44276-025-00128-3\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"BJC reports","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1038/s44276-025-00128-3","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
A novel multigene panel (Sig27) robustly predicts poor prognosis of renal cell carcinoma via high-level associations with immunosuppressive features.
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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