Liu Yaqian, Zhang Ming, Sun Jie, Zhang Jinyuan, Gu Boshi, Li Jun, Pan Bo, Zhao Haidong
Department of Breast Surgery, The Second Affiliated Hospital of Dalian Medical University Dalian, Liaoning, China.
Department of Pharmacy, The Second Affiliated Hospital of Dalian Medical University Dalian, Liaoning, China.
Am J Transl Res. 2024 Sep 15;16(9):4355-4378. doi: 10.62347/VIXN9362. eCollection 2024.
The immune status of the tumor microenvironment significantly impacts the clinical prognosis of triple-negative breast cancer (TNBC). The involvement of long noncoding RNAs (lncRNAs) in tumor immune infiltration is widely acknowledged. Therefore, it is crucial to explore the role of significant immune-related lncRNAs in TNBC.
We acquired RNA, single-cell sequencing, and clinical information on TNBC from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases. To identify immune-related lncRNAs, immune infiltration subgroups were determined and verified using single-sample gene-set enrichment analysis, non-negative matrix factorization, and weighted gene co-expression network analysis. CIBERSORTx, deconvolution, drug sensitivity, and Scissor analyses revealed that differences in cell type and drug efficacy were associated with immune grouping.
TNBC samples were classified into immune-desert (cold) and immune-inflamed (hot) subgroups based on a lncRNA model (including LINC01550, LY86-AS1, LINC00494, LINC00877, CHRM3-AS2, HCP5, MIR155HG, and PIK3CD-AS1). Furthermore, using in vitro experiments, we found that LINC01550 promoted malignant phenotypes, including proliferation, survival, and migration of TNBC. The immune-inflamed subgroup exhibited significantly lower half-maximal inhibitory concentration values for common anti-tumor drugs, including palbociclib, ribociclib, mitoxantrone, and sorafenib (T-test, P < 0.001). This may be related to the fact that the immune-inflamed subgroup has more plasmacytoid dendritic cells (pDCs) and B cells than those in immune-desert subgroups (P < 0.001).
Differences in specific cell infiltration can lead to increased sensitivity of the immune-inflamed subgroup to anti-tumor drugs. The proposed lncRNA model holds great promise to assess the immune landscapes and therapeutic reactions of TNBC patients.
肿瘤微环境的免疫状态对三阴性乳腺癌（TNBC）的临床预后有显著影响。长链非编码RNA（lncRNA）参与肿瘤免疫浸润已得到广泛认可。因此，探索重要的免疫相关lncRNA在TNBC中的作用至关重要。
我们从癌症基因组图谱（TCGA）和基因表达综合数据库（GEO）获取了TNBC的RNA、单细胞测序及临床信息。为鉴定免疫相关lncRNA，使用单样本基因集富集分析、非负矩阵分解和加权基因共表达网络分析来确定并验证免疫浸润亚组。CIBERSORTx、反卷积、药物敏感性和Scissor分析表明，细胞类型和药物疗效的差异与免疫分组相关。
基于lncRNA模型（包括LINC01550、LY86-AS1、LINC00494、LINC00877、CHRM3-AS2、HCP5、MIR155HG和PIK3CD-AS1），TNBC样本被分为免疫荒漠（冷）和免疫炎症（热）亚组。此外，通过体外实验，我们发现LINC01550促进了TNBC的恶性表型，包括增殖、存活和迁移。免疫炎症亚组对包括帕博西尼、瑞博西尼、米托蒽醌和索拉非尼在内的常见抗肿瘤药物的半数最大抑制浓度值显著更低（T检验，P < 0.001）。这可能与免疫炎症亚组比免疫荒漠亚组有更多浆细胞样树突状细胞（pDC）和B细胞有关（P < 0.001）。
特定细胞浸润的差异可导致免疫炎症亚组对抗肿瘤药物的敏感性增加。所提出的lncRNA模型在评估TNBC患者的免疫格局和治疗反应方面具有很大潜力。
