Medical Laboratory Science, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400042, China.
Clinical Laboratory, Chongqing Nanchuan Maternity and Child Healthcare Hospital, Chongqing, 408400, China.
Clin Transl Oncol. 2022 Oct;24(10):1986-1997. doi: 10.1007/s12094-022-02857-0. Epub 2022 Jun 23.
Prostate adenocarcinoma (PRAD) is a high incidence of malignant tumor of the urinary system and the second most common male cancer in the world. Immune checkpoint inhibitor (ICIS) therapy is becoming a new hope for cancer treatment.
To realize the possibility of PRAD patients benefiting from ICIS treatment, we analyzed the mutation spectrum of all PRAD patients, calculated the TMB of each PRAD patient, and divided the patients into high TMB group and low TMB group. Differentially expressed genes (DEGs) between the two groups were identified and path analysis was carried out. The immune cell infiltration of each PRAD patient was evaluated and survival analysis was performed to explore the effect of immune cell infiltration on the prognosis.
We found that high TMB was associated with better survival outcomes, with higher TMB scores in young patients, T2 and N0 patients. 28 hub genes were screened by the overlap between 229 DEGs and immune-related genes. T cells CD8 and CD4 memory activated in the high TMB group were higher than those in the low TMB group, while Mast cells resting in the low TMB group were higher than that in the high TMB group. High neutrophil infiltration is associated with poor prognosis in patients with PRAD. Finally, from the immune genes used to construct the prognostic risk model of TMB, it is found that CHP2 and NRG1 are independent prognostic factors of PRAD.
This study provides new insights into the immune microenvironment and potential immunotherapy of PRAD.
前列腺腺癌（PRAD）是泌尿系统高发的恶性肿瘤，也是全球第二大常见男性癌症。免疫检查点抑制剂（ICIS）治疗正在成为癌症治疗的新希望。
为了实现 PRAD 患者从 ICIS 治疗中获益的可能性，我们分析了所有 PRAD 患者的突变谱，计算了每位 PRAD 患者的 TMB，并将患者分为高 TMB 组和低 TMB 组。鉴定两组之间的差异表达基因（DEGs），并进行路径分析。评估每位 PRAD 患者的免疫细胞浸润情况，并进行生存分析，以探讨免疫细胞浸润对预后的影响。
我们发现高 TMB 与更好的生存结果相关，年轻患者、T2 和 N0 患者的 TMB 评分更高。通过 229 个 DEGs 与免疫相关基因的重叠，筛选出 28 个枢纽基因。高 TMB 组中 CD8 和 CD4 记忆激活的 T 细胞高于低 TMB 组，而低 TMB 组中静止的肥大细胞高于高 TMB 组。高中性粒细胞浸润与 PRAD 患者的预后不良相关。最后，从用于构建 TMB 预后风险模型的免疫基因中发现，CHP2 和 NRG1 是 PRAD 的独立预后因素。
本研究为 PRAD 的免疫微环境和潜在免疫治疗提供了新的见解。
