International Journal of Molecular Medical Science, 2024, Vol.14, No.5, 293-304 http://medscipublisher.com/index.php/ijmms 293 Feature Review Open Access Mapping the Tumor Microenvironment in Colon Cancer with Spatial Transcriptomics Yanru Zhang, Yuhao Deng, Min Zhang, Xin Wang, Fang Wang Institute of Precision Medicine, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510080, Guangdong, China Corresponding author: wangf359@mail.sysu.edu.cn International Journal of Molecular Medical Science, 2024, Vol.14, No.5 doi: 10.5376/ijmms.2024.14.0030 Received: 10 Aug., 2024 Accepted: 15 Sep., 2024 Published: 28 Sep., 2024 Copyright © 2024 Zhang et al., This is an open access article published under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Preferred citation for this article: Zhang Y.R., Deng Y.H., Zhang M., Wang X., and Wang F., 2024, Mapping the tumor microenvironment in colon cancer with spatial transcriptomics, International Journal of Molecular Medical Science, 14(5): 293-304 (doi: 10.5376/ijmms.2024.14.0030) Abstract The tumor microenvironment (TME) in colon cancer is a complex and dynamic entity that plays a critical role in tumor progression, metastasis, and response to therapy. Spatial transcriptomics has emerged as a powerful technology to map the spatial distribution of gene expression within the TME, providing unprecedented insights into the cellular and molecular heterogeneity of tumors. This feature review paper aims to explore the advancements in spatial transcriptomics and its application in understanding the TME of colon cancer. We will discuss various spatial profiling technologies, including imaging-based approaches and next-generation sequencing, that enable high-resolution mapping of gene expression. The review will highlight how these technologies have been used to identify distinct cellular niches, uncover spatially-resolved gene expression patterns, and elucidate the interactions between cancer cells and their microenvironment. Furthermore, we will examine the implications of these findings for cancer prognosis, treatment stratification, and the development of precision therapies. By integrating spatial transcriptomics with other omics data, we can achieve a more comprehensive understanding of the TME, paving the way for novel therapeutic targets and improved clinical outcomes for colon cancer patients. Keywords Tumor microenvironment; Colon cancer; Spatial transcriptomics; Gene expression, Heterogeneity; Precision therapy; Spatial profiling 1 Introduction CThe tumor microenvironment (TME) is a complex and dynamic ecosystem composed of cancer cells, stromal cells, immune cells, and extracellular matrix components. It plays a crucial role in tumor progression, metastasis, and response to therapy. Understanding the TME is essential for developing effective cancer treatments and improving patient outcomes. Recent advancements in spatial transcriptomics (ST) have provided unprecedented insights into the spatial organization and heterogeneity of the TME, enabling researchers to map gene expression patterns within the tissue context (Hu et al., 2022; Ospina et al., 2022; Yu et al., 2022). Spatial transcriptomics technologies have been instrumental in characterizing the spatial heterogeneity of various cancers, including colon cancer. These technologies allow for the simultaneous capture of gene expression data and spatial information, facilitating the identification of distinct cellular neighborhoods and their interactions within the TME (Andersson et al., 2021; Elosua-Bayes et al., 2021; Price et al., 2022). By integrating spatial transcriptomics with other high-throughput sequencing methods, researchers can gain a comprehensive understanding of the molecular and cellular landscape of tumors, which is critical for identifying novel therapeutic targets and biomarkers (Berglund et al., 2018; Wang et al., 2022; Thrane et al., 2018; Wang et al., 2021). This study aims to provide a valuable resource for researchers and clinicians interested in leveraging spatial transcriptomics to advance our understanding of the TME in colon cancer and improve therapeutic strategies. 2 Colon Cancer and Tumor Microenvironment 2.1 Overview of colon cancer pathogenesis Colon cancer, also known as colorectal cancer (CRC), is a major health concern worldwide. It arises from the epithelial cells lining the colon or rectum and progresses through a series of well-defined stages, from benign adenomas to malignant carcinomas. The pathogenesis of colon cancer involves a complex interplay of genetic
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