ARHGAP11A Is a Novel Prognostic and Predictive Biomarker Correlated with Immunosuppressive Microenvironment in Clear Cell Renal Cell Carcinoma.
ARHGAP11A Is a Novel Prognostic and Predictive Biomarker Correlated with Immunosuppressive Microenvironment in Clear Cell Renal Cell Carcinoma.
复制标题
DOI：
10.3390/ijms24097755
复制
发表时间：
2023-04-24
影响因子：
5.6
通讯作者：
Zheng, Junfang
中科院分区：
文献类型：
--
作者：
Yang, Huihui;Zhang, Hongning;Zhang, Liuxu;Tusuphan, Paizigul;Zheng, Junfang
透明细胞肾细胞癌（ccRCC）是一种高度免疫原性的肿瘤，并且免疫功能障碍与ccRCC不良预后相关。据报道，RhoGAPs家族影响ccRCC的发展，但其在ccRCC的免疫和预后预测中的作用尚不清楚。在本研究中，我们发现ARHGAP 11 A是33种RhoGAP中唯一的独立危险因素（风险比[HR] 1.949，95%置信区间[CI] 1.364-2.785）。高ARHGAP 11 A水平与较短的总生存期相关（OS，HR 2.040，95% CI 1.646-3.417），ARHGAP 11 A是ccRCC的预后生物标志物。ARHGAP 11 A基因敲低可抑制肾细胞癌（RCC）细胞增殖、集落形成和迁移，提示ARHGAP 11 A对RCC的发展具有促进作用。从机制上讲，ARHGAP 11 A可能有助于抑制肿瘤免疫微环境（TIME）。高ARHGAP 11 A水平与免疫抑制细胞（包括辅助性T细胞2（Th 2）细胞、调节性T细胞（Treg）细胞、髓源性抑制细胞（MDSC）和M2巨噬细胞）浸润、免疫抑制途径（IL 6-JAK-STAT 3信号传导和IFNγ应答）激活和抑制性免疫检查点（IC）表达相关。ARHGAP 11 A可促进T细胞耗竭，诱导免疫逃逸。低ARHGAP 11 A水平的ccRCC患者更适合免疫检查点抑制剂（ICI）治疗，而高ARHGAP 11 A水平的患者可能受益于ARHGAP 11 A阻断和ICI的联合治疗。总之，ARHGAP 11 A可能作为一种新的预后标志物，治疗靶点，并预测ccRCC对ICIs治疗的临床反应。
Clear cell renal cell carcinoma (ccRCC) is a highly immunogenic tumor and immune dysfunction is associated with ccRCC poor prognosis. The RhoGTPase-activating proteins (RhoGAPs) family was reported to affect ccRCC development, but its role in immunity and prognosis prediction for ccRCC remain unknown. In the current study, we found ARHGAP11A was the only independent risk factor among 33 RhoGAPs (hazard ratio [HR] 1.949, 95% confidence interval [CI] 1.364–2.785). High ARHGAP11A level was associated with shorter overall survival (OS, HR 2.040, 95% CI 1.646–3.417) and ARHGAP11A is a prognostic biomarker for ccRCC. ARHGAP11A knockdown suppressed renal cell carcinoma (RCC) cell proliferation, colony formation, and migration, suggesting the promoting role of ARHGAP11A on RCC development. Mechanistically, ARHGAP11A might contribute to the suppressive tumor immune microenvironment (TIME). High ARHGAP11A level was correlated with infiltration of immunosuppressive cells (including T helper 2 (Th2) cells, regulatory T (Treg) cells, myeloid derived suppressor cells (MDSC), and M2 macrophage cells), activation of immunosuppressive pathways (IL6-JAK-STAT3 signaling and IFNγ response), and expression of inhibitory immune checkpoints (ICs). ARHGAP11A could promote T cell exhaustion and induce immune escape. ccRCC patients with low ARHGAP11A level were more suitable for immune checkpoint inhibitors (ICIs) therapy, while those with high ARHGAP11A level might benefit from a combination of ARHGAP11A blockade and ICIs. In all, ARHGAP11A might serve as a novel prognostic marker, therapeutic target, and predictor in the clinical response to ICIs therapy for ccRCC.
登录
查看更多内容
CTLA4对透明细胞肾细胞癌（CCRCC）的预后价值高的肿瘤淋巴细胞的景观具有深远的影响。
影响因子：
5.8
作者：
Liu S;Wang F;Tan W;Zhang L;Dai F;Wang Y;Fan Y;Yuan M;Yang D;Zheng Y;Deng Z;Liu Y;Cheng Y
通讯作者：
Cheng Y
DOI：
10.1038/s41571-020-00455-z
发表时间：
2021-04
期刊：
Nature reviews. Clinical oncology
影响因子：
--
作者：
Braun DA;Bakouny Z;Hirsch L;Flippot R;Van Allen EM;Wu CJ;Choueiri TK
通讯作者：
Choueiri TK
影响因子：
4.9
作者：
Ferreira, Marcel R.;Santos, Gerson A.;Zambuzzi, Willian F.
通讯作者：
Zambuzzi, Willian F.
影响因子：
4.7
作者：
Fang Z;Sun Q;Yang H;Zheng J
通讯作者：
Zheng J
肾细胞癌患者中偏斜的T-helper（Th）1/2和Th17/T调节细胞平衡。
影响因子：
3.4
作者：
Li L;Yang C;Zhao Z;Xu B;Zheng M;Zhang C;Min Z;Guo J;Rong R
通讯作者：
Rong R