Lin Anqi, Fang Jianbo, Cheng Quan, Liu Zaoqu, Luo Peng, Zhang Jian
Department of Oncology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, People's Republic of China.
Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China.
J Inflamm Res. 2022 Sep 23;15:5541-5555. doi: 10.2147/JIR.S379016. eCollection 2022.
The advent of immune checkpoint inhibitors (ICIs) is a revolutionary breakthrough. However, without the selection of a specific target population, the response rate of ICI therapy in lung adenocarcinoma (LUAD) is low, so a clinical challenge has arisen in effectively using biomarkers to determine which patients can benefit from ICI therapy.
In this study, patients were divided according to whether or not nonsynonymous mutations were present in the BCR signaling pathway, and univariate and multivariate Cox regression models were established based on a LUAD cohort treated with ICIs (Miao-LUAD). Then the relationship between the mutation status of the BCR signaling pathway and the prognosis of immunotherapy was examined. Finally, data from The Cancer Genome Atlas (TCGA) LUAD cohort, the Rizvi-LUAD, the Samstein-LUAD, and the Zhujiang Hospital of Southern Medical University LUAD (Local-LUAD) cohort were combined, and the mutation panorama, immunogenicity, tumor microenvironment (TME) and pathway enrichment analysis between the BCR signaling pathway mutant group (BCR signaling MUT) and the BCR signaling pathway wild group (BCR signaling WT) were comprehensively compared.
It was found that, compared with the BCR signaling WT, the BCR signaling MUT had a significantly improved progression-free survival (PFS) rate and overall survival (OS) rate, higher immunogenicity (tumor mutational burden, neoantigen load, and DNA damage response signaling mutations), and anti-tumor immune microenvironment.
These results revealed that the mutation state of the BCR signaling pathway has potential as a biomarker to predict the efficacy of ICIs in LUAD.
免疫检查点抑制剂（ICI）的出现是一项革命性突破。然而，在未选择特定目标人群的情况下，ICI治疗在肺腺癌（LUAD）中的缓解率较低，因此在有效利用生物标志物来确定哪些患者可从ICI治疗中获益方面出现了临床挑战。
在本研究中，根据BCR信号通路中是否存在非同义突变对患者进行分组，并基于接受ICI治疗的LUAD队列（Miao-LUAD）建立单变量和多变量Cox回归模型。然后研究BCR信号通路的突变状态与免疫治疗预后之间的关系。最后，合并来自癌症基因组图谱（TCGA）LUAD队列、Rizvi-LUAD、Samstein-LUAD以及南方医科大学珠江医院LUAD（Local-LUAD）队列的数据，全面比较BCR信号通路突变组（BCR信号MUT）和BCR信号通路野生组（BCR信号WT）之间的突变全景、免疫原性、肿瘤微环境（TME）和通路富集分析。
发现与BCR信号WT相比，BCR信号MUT的无进展生存期（PFS）率和总生存期（OS）率显著提高，免疫原性更高（肿瘤突变负担、新抗原负荷和DNA损伤反应信号突变），且具有抗肿瘤免疫微环境。
这些结果表明，BCR信号通路的突变状态有潜力作为预测ICI在LUAD中疗效的生物标志物。
