Integrating microarray-based spatial transcriptomics and RNA-seq reveals tissue architecture in colorectal cancer

IF 8.6 2区 计算机科学 Q1 COMPUTER SCIENCE, THEORY & METHODS Journal of Big Data Pub Date : 2024-09-17 DOI:10.1186/s40537-024-00992-9
Zheng Li, Xiaojie Zhang, Chongyuan Sun, Zefeng Li, He Fei, Dongbing Zhao
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Abstract

Background

The tumor microenvironment (TME) provides a region for intricate interactions within or between immune and non-immune cells. We aimed to reveal the tissue architecture and comprehensive landscape of cells within the TME of colorectal cancer (CRC).

Methods

Fresh frozen invasive adenocarcinoma of the large intestine tissue from 10× Genomics Datasets was obtained from BioIVT Asterand. The integration of microarray-based spatial transcriptomics (ST) and RNA sequencing (RNA-seq) was applied to characterize gene expression and cell landscape within the TME of CRC tissue architecture. Multiple R packages and deconvolution algorithms including MCPcounter, XCELL, EPIC, and ESTIMATE methods were performed for further immune distribution analysis.

Results

The subpopulations of immune and non-immune cells within the TME of the CRC tissue architecture were appropriately annotated. According to ST and RNA-seq analyses, a heterogeneous spatial atlas of gene distribution and cell landscape was comprehensively characterized. We distinguished between the cancer and stromal regions of CRC tissues. As expected, epithelial cells were located in the cancerous region, whereas fibroblasts were mainly located in the stroma. In addition, the fibroblasts were further subdivided into two subgroups (F1 and F2) according to the differentially expressed genes (DEGs), which were mainly enriched in pathways including hallmark-oxidative-phosphorylation, hallmark-e2f-targets and hallmark-unfolded-protein-response. Furthermore, the top 5 DEGs, SPP1, CXCL10, APOE, APOC1, and LYZ, were found to be closely related to immunoregulation of the TME, methylation, and survival of CRC patients.

Conclusions

This study characterized the heterogeneous spatial landscape of various cell subtypes within the TME of the tissue architecture. The TME-related roles of fibroblast subsets addressed the potential crosstalk among diverse cells.

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整合基于芯片的空间转录组学和 RNA-seq 技术揭示结直肠癌的组织结构
背景肿瘤微环境(TME)为免疫细胞和非免疫细胞内部或之间错综复杂的相互作用提供了一个区域。我们的目的是揭示结直肠癌(CRC)TME内的组织结构和细胞的综合景观。方法从BioIVT Asterand公司的10×基因组学数据集中获得新鲜冷冻的大肠浸润性腺癌组织。应用基于微阵列的空间转录组学(ST)和 RNA 测序(RNA-seq)的整合来描述 CRC 组织结构中 TME 内的基因表达和细胞景观。结果 对 CRC 组织结构 TME 中的免疫和非免疫细胞亚群进行了适当的注释。根据ST和RNA-seq分析,全面描述了基因分布和细胞景观的异质性空间图谱。我们区分了 CRC 组织的癌区和基质区。不出所料,上皮细胞位于癌区,而成纤维细胞主要位于基质区。此外,根据差异表达基因(DEGs),成纤维细胞被进一步细分为两个亚组(F1和F2),主要富集在包括霍尔马克氧化磷酸化、霍尔马克-e2f-靶标和霍尔马克未折叠蛋白反应等通路中。此外,研究还发现前 5 个 DEGs(SPP1、CXCL10、APOE、APOC1 和 LYZ)与 TME 的免疫调节、甲基化和 CRC 患者的生存密切相关。成纤维细胞亚群在 TME 中的相关作用揭示了不同细胞之间的潜在串扰。
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来源期刊
Journal of Big Data
Journal of Big Data Computer Science-Information Systems
CiteScore
17.80
自引率
3.70%
发文量
105
审稿时长
13 weeks
期刊介绍: The Journal of Big Data publishes high-quality, scholarly research papers, methodologies, and case studies covering a broad spectrum of topics, from big data analytics to data-intensive computing and all applications of big data research. It addresses challenges facing big data today and in the future, including data capture and storage, search, sharing, analytics, technologies, visualization, architectures, data mining, machine learning, cloud computing, distributed systems, and scalable storage. The journal serves as a seminal source of innovative material for academic researchers and practitioners alike.
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