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单细胞转录组分析揭示了免疫微环境的变化,并深入了解了从 DCIS 到 IDC 的转变,以及与预后相关的基因。

Single-cell transcriptome analysis reveals immune microenvironment changes and insights into the transition from DCIS to IDC with associated prognostic genes.

机构信息

School of Computer Science and Technology, Hainan University, Haikou, 570228, China.

International Business School, Hainan University, Haikou, 570228, China.

出版信息

J Transl Med. 2024 Oct 3;22(1):894. doi: 10.1186/s12967-024-05706-6.

Abstract

BACKGROUND

Ductal carcinoma in situ (DCIS) of the breast is an early stage of breast cancer, and preventing its progression to invasive ductal carcinoma (IDC) is crucial for the early detection and treatment of breast cancer. Although single-cell transcriptome analysis technology has been widely used in breast cancer research, the biological mechanisms underlying the transition from DCIS to IDC remain poorly understood.

RESULTS

We identified eight cell types through cell annotation, finding significant differences in T cell proportions between DCIS and IDC. Using this as a basis, we performed pseudotime analysis on T cell subpopulations, revealing that differentially expressed genes primarily regulate immune cell migration and modulation. By intersecting WGCNA results of T cells highly correlated with the subtypes and the differentially expressed genes, we identified six key genes: FGFBP2, GNLY, KLRD1, TYROBP, PRF1, and NKG7. Excluding PRF1, the other five genes were significantly associated with overall survival in breast cancer, highlighting their potential as prognostic biomarkers.

CONCLUSIONS

We identified immune cells that may play a role in the progression from DCIS to IDC and uncovered five key genes that can serve as prognostic markers for breast cancer. These findings provide insights into the mechanisms underlying the transition from DCIS to IDC, offering valuable perspectives for future research. Additionally, our results contribute to a better understanding of the biological processes involved in breast cancer progression.

摘要

背景

乳腺导管原位癌(DCIS)是乳腺癌的早期阶段,防止其进展为浸润性导管癌(IDC)对于乳腺癌的早期发现和治疗至关重要。虽然单细胞转录组分析技术已广泛应用于乳腺癌研究,但 DCIS 向 IDC 转化的生物学机制仍知之甚少。

结果

通过细胞注释,我们鉴定了 8 种细胞类型,发现 DCIS 和 IDC 之间 T 细胞比例存在显著差异。在此基础上,我们对 T 细胞亚群进行了伪时间分析,发现差异表达基因主要调节免疫细胞的迁移和调节。通过与 T 细胞高度相关的亚型和差异表达基因的 WGCNA 结果进行交集,我们鉴定出了 6 个关键基因:FGFBP2、GNLY、KLRD1、TYROBP、PRF1 和 NKG7。除了 PRF1 之外,其他 5 个基因与乳腺癌的总生存率显著相关,这表明它们可能是预后生物标志物。

结论

我们鉴定出了可能在 DCIS 向 IDC 进展中发挥作用的免疫细胞,并发现了 5 个可以作为乳腺癌预后标志物的关键基因。这些发现为 DCIS 向 IDC 转化的机制提供了新的见解,为未来的研究提供了有价值的思路。此外,我们的研究结果有助于更好地理解乳腺癌进展过程中的生物学过程。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bdb5/11448450/3cd1b84d348c/12967_2024_5706_Fig1_HTML.jpg

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