Deng Dingshan, Li Xiaowen, Qi Tiezheng, Dai Yuanqing, Liu Neng, Li Huihuang
Department of Urology, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China.
National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China.
Front Pharmacol. 2023 May 4;14:1187700. doi: 10.3389/fphar.2023.1187700. eCollection 2023.
Although the durable efficacy of immune checkpoint inhibitors (ICIs) in BLCA has been confirmed in numerous studies, not all patients benefit from their application in the clinic. Platelets are increasingly being found to be closely associated with cancer progression and metastasis; however, their comprehensive role in BLCA remains unclear. We comprehensively explored platelet expression patterns in BLCA patients using an integrated set of 244 related genes. Correlations between these platelet patterns with tumor microenvironment (TME) subtypes, immune characteristics and immunotherapy efficacies were explored. In addition, a platelet risk score (PRS) was generated for individual prognosis and verified the ability to predict prognosis, precise TME phenotypes, and immunotherapy efficacies. Genes were clustered into two patterns that represented different TME phenotypes and had the ability to predict immunotherapy efficacy. We constructed a PRS that could predict individual prognosis with satisfactory accuracy using TCGA-BLCA. The results remained consistent when PRS was validated in the GSE32894 and Xiangya cohort. Moreover, we found that our PRS was positively related to tumor-infiltrating lymphocytes (TILs) in the TCGA-BLCA and Xiangya cohort. As expected, patients with higher PRS exhibited more sensitive to immunotherapy than patients with lower PRS. Finally, we discovered that a high PRS indicated a basal subtype of BLCA, whereas a low PRS indicated a luminal subtype. Platelet-related genes could predict TME phenotypes in BLCA. We constructed a PRS that could predict the TME, prognosis, immunotherapy efficacy, and molecular subtypes in BLCA.
尽管免疫检查点抑制剂（ICIs）在膀胱癌（BLCA）中的持久疗效已在众多研究中得到证实，但并非所有患者在临床应用中都能从中获益。越来越多的研究发现血小板与癌症进展和转移密切相关；然而，它们在膀胱癌中的综合作用仍不清楚。我们使用一组244个相关基因全面探索了膀胱癌患者的血小板表达模式。探讨了这些血小板模式与肿瘤微环境（TME）亚型、免疫特征和免疫治疗疗效之间的相关性。此外，还生成了一个血小板风险评分（PRS）用于个体预后评估，并验证了其预测预后、精确TME表型和免疫治疗疗效的能力。基因被聚类为两种模式，代表不同的TME表型，并具有预测免疫治疗疗效的能力。我们构建了一个PRS，使用TCGA-BLCA数据集能够以令人满意的准确性预测个体预后。在GSE32894和湘雅队列中验证PRS时，结果保持一致。此外，我们发现我们的PRS与TCGA-BLCA和湘雅队列中的肿瘤浸润淋巴细胞（TILs）呈正相关。正如预期的那样，高PRS患者比低PRS患者对免疫治疗表现出更高的敏感性。最后，我们发现高PRS表明膀胱癌的基底亚型，而低PRS表明管腔亚型。血小板相关基因可以预测膀胱癌中的TME表型。我们构建了一个PRS，它可以预测膀胱癌中的TME、预后、免疫治疗疗效和分子亚型。
