Zheng Yuanyuan, Wang Kainan, Li Ning, Zhang Qianran, Chen Fengxi, Li Man
Department of Oncology, The Second Hospital of Dalian Medical University, Dalian, China.
Department of Foreign Language, Dalian Medical University, Dalian, China.
Front Surg. 2022 May 17;9:837848. doi: 10.3389/fsurg.2022.837848. eCollection 2022.
Breast cancer (BC) is the most common cancer among women worldwide, with enormous heterogeneity. Pyroptosis has a significant impact on the development and progression of tumors. Nonetheless, the possible correlation between pyroptosis-related genes (PRGs) and the BC immune microenvironment has yet to be investigated.
In The Cancer Genome Atlas Breast Cancer cohort, 38 PRGs were shown to be significantly different between malignant and non-malignant breast tissues. The 38 PRGs' consensus clustering grouped 1,089 individuals into two pyroptosis-related (PR) patterns. Using univariate and LASSO-Cox analyses, a PR five-gene predictive signature was constructed based on the differentially expressed genes between two clusters. The tools estimation of stromal and immune cells in malignant tumours using expression data (ESTIMATE), cell type identification by estimating relative subsets Of RNA transcripts (CIBERSORT), and single-sample gene set enrichment analysis (ssGSEA) were used to investigate the BC tumor microenvironment (TME).
In TME, the two PR clusters displayed distinct clinicopathological characteristics, survival outcomes, and immunocyte infiltration features. The developed five-signature model (SEMA3B, IGKC, KLRB1, BIRC3, and PSME2) classified BC patients into two risk groups based on the estimated median risk score. Patients in the low-scoring category had a higher chance of survival and more extensive immunocyte infiltration. An external validation set can yield similar results.
Our data suggest that PRGs have a significant impact on the BC immunological microenvironment. The PR clusters and associated predictive signature stimulate additional research into pyroptosis in order to optimize therapeutic strategies for BC patients and their responses to immune therapy.
乳腺癌（BC）是全球女性中最常见的癌症，具有极大的异质性。细胞焦亡对肿瘤的发生和发展具有重要影响。然而，细胞焦亡相关基因（PRGs）与BC免疫微环境之间的潜在相关性尚未得到研究。
在癌症基因组图谱乳腺癌队列中，38个PRGs在恶性和非恶性乳腺组织之间存在显著差异。这38个PRGs的一致性聚类将1089名个体分为两种细胞焦亡相关（PR）模式。使用单变量和LASSO-Cox分析，基于两个聚类之间的差异表达基因构建了一个PR五基因预测特征。使用基于表达数据估计恶性肿瘤中的基质和免疫细胞（ESTIMATE）、通过估计RNA转录本的相对子集进行细胞类型鉴定（CIBERSORT）以及单样本基因集富集分析（ssGSEA）来研究BC肿瘤微环境（TME）。
在TME中，两个PR聚类表现出不同的临床病理特征、生存结果和免疫细胞浸润特征。开发的五特征模型（SEMA3B、IGKC、KLRB1、BIRC3和PSME2）根据估计的中位风险评分将BC患者分为两个风险组。低评分组的患者生存机会更高，免疫细胞浸润更广泛。外部验证集可得出类似结果。
我们的数据表明PRGs对BC免疫微环境有显著影响。PR聚类和相关的预测特征激发了对细胞焦亡的进一步研究，以优化BC患者的治疗策略及其对免疫治疗的反应。
