Department of Radiation Oncology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China.
Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai 200032, China.
J Immunol Res. 2022 Aug 9;2022:7978042. doi: 10.1155/2022/7978042. eCollection 2022.
The cytosolic DNA sensor cyclic GMP-AMP synthase (cGAS) plays critical functions in innate immune responses via the production of the second messenger cyclic guanosine monophosphate-adenosine monophosphate (cGAMP), which stimulates the adaptor stimulator of interferon genes (STING). However, the clinical relevance and prognostic value of the cGAS-STING pathway in human cancers remains largely unexplored.
A gene signature related to the cGAS-STING score was identified. The pan-cancer landscape of cGAS-STING expression was calculated using the RNAseq data acquired from the TCGA cohort. Tumor-infiltrating immune cells (TIICs) were determined by the ssGSEA method. Kaplan-Meier curves, Cox regression analyses, and the area under the curve (AUC) were employed to decipher the predictive value of cGAS-STING risk score and TIICs across several human cancers.
Most tumor tissues displayed a higher cGAS-STING score compared with their corresponding nontumor tissues, except for prostate adenocarcinoma (PRAD) and uterine corpus endometrial carcinoma (UCEC). Higher cGAS-STING score was closely associated with poor clinical outcome of kidney renal clear cell carcinoma (KIRC) and kidney renal papillary cell carcinoma (KIRP), whereas the cGAS-STING score predicted a better prognosis in pheochromocytoma and paraganglioma (PCPG). Enrichment analysis showed that cGAS-STING was profoundly implicated in diverse immune-related pathways in KIRC, KIRP, and PCPG. Significant positive correlations were noticed between cGAS-STING score and TIICs, including activated CD8+ T cells, activated CD4+ T cells, monocytes, and mast cells. Finally, the cGAS-STING score was revealed to be an independent prognostic factor for KIRC patients and possessed a strong predictive power for the prognostic evaluation of KIRC and KIRP patients.
We constructed a cGAS-STING gene signature to predict survival and tumor immunity across human cancers, which can serve as a novel prognostic indicator and therapeutic target, especially in KIRC and KIRP.
细胞质 DNA 传感器环鸟苷酸-腺苷酸合酶 (cGAS) 通过产生第二信使环鸟苷酸-单磷酸-腺苷单磷酸 (cGAMP) 发挥关键作用，从而刺激干扰素基因刺激物 (STING) 的衔接物。然而，cGAS-STING 途径在人类癌症中的临床相关性和预后价值在很大程度上仍未得到探索。
确定了与 cGAS-STING 评分相关的基因特征。使用从 TCGA 队列获得的 RNAseq 数据计算了 pan-cancer 中的 cGAS-STING 表达图谱。通过 ssGSEA 方法确定肿瘤浸润免疫细胞 (TIIC)。使用 Kaplan-Meier 曲线、Cox 回归分析和曲线下面积 (AUC) 来破译 cGAS-STING 风险评分和 TIIC 在多种人类癌症中的预测价值。
除了前列腺腺癌 (PRAD) 和子宫体子宫内膜癌 (UCEC) 外，大多数肿瘤组织的 cGAS-STING 评分均高于其相应的非肿瘤组织。较高的 cGAS-STING 评分与肾透明细胞癌 (KIRC) 和肾乳头细胞癌 (KIRP) 的不良临床结局密切相关，而 cGAS-STING 评分预测嗜铬细胞瘤和副神经节瘤 (PCPG) 的预后较好。富集分析表明，cGAS-STING 与 KIRC、KIRP 和 PCPG 中的多种免疫相关途径密切相关。cGAS-STING 评分与 TIICs 之间存在显著的正相关，包括激活的 CD8+T 细胞、激活的 CD4+T 细胞、单核细胞和肥大细胞。最后，cGAS-STING 评分被揭示为 KIRC 患者的独立预后因素，并且对 KIRC 和 KIRP 患者的预后评估具有强大的预测能力。
我们构建了一个 cGAS-STING 基因特征，用于预测人类癌症的生存和肿瘤免疫，它可以作为一种新的预后指标和治疗靶点，特别是在 KIRC 和 KIRP 中。
