<br>RYR2突变在乳腺癌中免疫意义的生物信息学分析,BioMed Research International

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RYR2突变在乳腺癌中免疫意义的生物信息学分析
BioMed Research International ( IF 2.6 ) Pub Date : 2021-11-03 , DOI: 10.1155/2021/8072796
Zhiquan Xu ₁ , Ling Xiang ₂ , Rong Wang ₃ , Yongfu Xiong ₄ , He Zhou ₅ , Haitao Gu ₁ , Jijian Wang ₁ , Linglong Peng ₁

Affiliation

背景。目前，免疫治疗广泛用于乳腺癌（BC）患者，肿瘤突变负荷（TMB）被认为是免疫治疗反应的一个有价值的独立预测因子。然而，BC 中特定的基因突变及其与 TMB 和肿瘤浸润免疫细胞的关系尚不完全清楚。方法。使用癌症基因组图谱 (TCGA) 和国际癌症基因组联盟 (ICGC) 数据集的数据进行全面的生物信息分析。通过Kaplan-Meier分析来分析生存曲线。单变量和多变量Cox回归分析用于预后分析。进行基因集富集分析（GSEA）以探索调控机制和功能。使用 CIBERSORT 算法计算肿瘤浸润免疫细胞分数。结果。我们分析了 TCGA 和 ICGC 数据集中的 BC 体细胞突变数据，发现两个队列中均报告了 19 个频繁突变基因，即 SPTA1、TTN、MUC17、MAP3K1、CDH1、FAT3、SYNE1、FLG、HMCN1、RYR2（ryanodine 受体 2） )、GATA3、MUC4、PIK3CA、KMT2C、TP53、PTEN、ZFHX4、MUC16 和 USH2A。其中，我们观察到RYR2突变与较高的TMB和更好的临床预后显着相关。此外，GSEA 揭示了 RYR2 突变丰富的信号通路与免疫相关通路相关。此外，基于CIBERSORT算法，我们发现RYR2突变通过富集CD8+ T细胞、活化的记忆CD4+ T细胞和M1巨噬细胞来增强抗肿瘤免疫反应。结论。 RYR2在BC中频繁突变，其突变与TMB增加、促进抗肿瘤免疫有关；因此，RYR2可以作为预测免疫反应的有价值的生物标志物。

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Bioinformatic Analysis of Immune Significance of RYR2 Mutation in Breast Cancer

Background. Currently, immunotherapy is widely used for breast cancer (BC) patients, and tumor mutation burden (TMB) is regarded as a valuable independent predictor of response to immunotherapy. However, specific gene mutations and their relationship with TMB and tumor-infiltrating immune cells in BC are not fully understood. Methods. Comprehensive bioinformatic analyses were performed using data from The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) datasets. Survival curves were analyzed via Kaplan-Meier analysis. Univariate and multivariate Cox regression analyses were used for prognosis analysis. Gene set enrichment analysis (GSEA) was performed to explore regulatory mechanisms and functions. The CIBERSORT algorithm was used to calculate the tumor-infiltrating immune cell fractions. Results. We analyzed somatic mutation data of BC from TCGA and ICGC datasets and found that 19 frequently mutated genes were reported in both cohorts, namely, SPTA1, TTN, MUC17, MAP3K1, CDH1, FAT3, SYNE1, FLG, HMCN1, RYR2 (ryanodine receptor 2), GATA3, MUC4, PIK3CA, KMT2C, TP53, PTEN, ZFHX4, MUC16, and USH2A. Among them, we observed that RYR2 mutation was significantly associated with higher TMB and better clinical prognosis. Moreover, GSEA revealed that RYR2 mutation-enriched signaling pathways were related to immune-associated pathways. Furthermore, based on the CIBERSORT algorithm, we found that RYR2 mutation enhanced the antitumor immune response by enriching CD8+ T cells, activated memory CD4+ T cells, and M1 macrophages. Conclusion. RYR2 is frequently mutated in BC, and its mutation is related to increased TMB and promotes antitumor immunity; thus, RYR2 may serve as a valuable biomarker to predict the immune response.

更新日期：2021-11-03

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