Zhao Yaqi, Wu Jie, Li Lan, Zhang Huibo, Zhang Haohan, Li Jing, Zhong Hao, Lei Tianyu, Jin Yan, Xu Bin, Song Qibin
Cancer Center, Renmin Hospital of Wuhan University, Wuhan, China.
Department of Bioinformatics, Wissenschaftszentrum Weihenstephan, Technical University of Munich, Freising, Germany.
Front Genet. 2022 Feb 10;13:820135. doi: 10.3389/fgene.2022.820135. eCollection 2022.
Mainstream application of cancer immunotherapy is hampered by the low response rate of most cancer patients. A novel immunotherapeutic target or a biomarker predicting response to immunotherapy needs to be developed. Guanylate-binding protein 1 (GBP1) is an interferon (IFN)-inducible guanosine triphosphatases (GTPases) involving inflammation and infection. However, the immunological effects of GBP1 in pan-cancer patients are still obscure. Using large-scale public data, we delineated the landscape of GBP1 across 33 cancer types. The correlation between GBP1 expression or mutation and immune cell infiltration was estimated by ESTIMATE, TIMER, xCell, and quanTIseq algorithms. GBP1-related genes and proteins were subjected to function enrichment analysis. Clustering analysis explored the relationship between GBP1 expression and anti-tumor immune phenotypes. We assessed the patient's response to immunotherapy using the tumor immune dysfunction and exclusion (TIDE) score and immunophenoscore (IPS). Furthermore, we validated the predictive power of GBP1 expression in four independent immunotherapy cohorts. GBP1 was differentially expressed in tumors and normal tissues in multiple cancer types. Distinct correlations existed between GBP1 expression and prognosis in cancer patients. GBP1 expression and mutation were positively associated with immune cell infiltration. Function enrichment analysis showed that GBP1-related genes were enriched in immune-related pathways. Positive correlations were also observed between GBP1 expression and the expression of immune checkpoints, as well as tumor mutation burden (TMB). Pan-cancer patients with higher GBP1 expression were more inclined to display "hot" anti-tumor immune phenotypes and had lower TIDE scores and higher immunophenoscore, suggesting that these patients had better responses to immunotherapy. Patients with higher GBP1 expression exhibited improved overall survival and clinical benefits in immunotherapy cohorts, including the Gide et al. cohort [area under the curve (AUC): 0.813], the IMvigor210 cohort (AUC: 0.607), the Lauss et al. cohort (AUC: 0.740), and the Kim et al. cohort (AUC: 0.793). This study provides comprehensive insights into the role of GBP1 in a pan-cancer manner. We identify GBP1 expression as a predictive biomarker for immunotherapy, potentially enabling more precise and personalized immunotherapeutic strategies in the future.
大多数癌症患者的低反应率阻碍了癌症免疫疗法的主流应用。需要开发一种新的免疫治疗靶点或预测免疫治疗反应的生物标志物。鸟苷酸结合蛋白1（GBP1）是一种干扰素（IFN）诱导的鸟苷三磷酸酶（GTPases），与炎症和感染有关。然而，GBP1在泛癌患者中的免疫效应仍不清楚。利用大规模公共数据，我们描绘了GBP1在33种癌症类型中的分布情况。通过ESTIMATE、TIMER、xCell和quanTIseq算法估计GBP1表达或突变与免疫细胞浸润之间的相关性。对GBP1相关基因和蛋白质进行功能富集分析。聚类分析探讨了GBP1表达与抗肿瘤免疫表型之间的关系。我们使用肿瘤免疫功能障碍和排除（TIDE）评分和免疫表型评分（IPS）评估患者对免疫治疗的反应。此外，我们在四个独立的免疫治疗队列中验证了GBP1表达的预测能力。GBP1在多种癌症类型的肿瘤组织和正常组织中存在差异表达。GBP1表达与癌症患者的预后存在明显相关性。GBP1表达和突变与免疫细胞浸润呈正相关。功能富集分析表明，GBP1相关基因富集于免疫相关途径。GBP1表达与免疫检查点的表达以及肿瘤突变负荷（TMB）之间也观察到正相关。GBP1表达较高的泛癌患者更倾向于表现出“热”的抗肿瘤免疫表型，TIDE评分较低，免疫表型评分较高，这表明这些患者对免疫治疗的反应更好。GBP1表达较高的患者在免疫治疗队列中表现出更好的总生存期和临床获益，包括吉德等人的队列[曲线下面积（AUC）：0.813]、IMvigor210队列（AUC：0.607）、劳斯等人的队列（AUC：0.740）以及金等人的队列（AUC：0.793）。本研究以泛癌方式全面深入地了解了GBP1的作用。我们将GBP-1表达确定为免疫治疗的预测生物标志物，有望在未来实现更精确和个性化的免疫治疗策略。
