Spatial omics technologies for understanding molecular status associated with cancer progression

Abstract

Cancer cells are generally exposed to numerous extrinsic stimulations in the tumor microenvironment. In this environment, cancer cells change their expression profiles to fight against circumstantial stresses, allowing their progression in the challenging tissue space. Technological advancements of spatial omics have had substantial influence on cancer genomics. This technical progress, especially that occurring in the spatial transcriptome, has been drastic and rapid. Here, we describe the latest spatial analytical technologies that have allowed omics feature characterization to retain their spatial and histopathological information in cancer tissues. Several spatial omics platforms have been launched, and the latest platforms finally attained single-cell level or even higher subcellular level resolution. We discuss several key papers elucidating the initial utility of the spatial analysis. In fact, spatial transcriptome analyses reveal comprehensive omics characteristics not only in cancer cells but also their surrounding cells, such as tumor infiltrating immune cells and cancer-associated fibroblasts. We also introduce several spatial omics platforms. We describe our own attempts to investigate molecular events associated with cancer progression. Furthermore, we discuss the next challenges in analyzing the multiomics status of cells, including their morphology and location. These novel technologies, in conjunction with spatial transcriptome analysis and, more importantly, with histopathology, will elucidate even novel key aspects of the intratumor heterogeneity of cancers. Such enhanced knowledge is expected to open a new path for overcoming therapeutic resistance and eventually to precisely stratify patients.

Keywords: cancer progression; multiomics; single‐cell resolution; spatial transcriptome; tumor microenvironment.

FIGURE 1

Sequencing‐based spatial transcriptome platforms. The workflows of Visium HD and STOmics are illustrated in (A) and (B), respectively.

FIGURE 2

Imaging‐based spatial transcriptome platforms. The Xenium, CosMx, and MERSCOPE workflows are shown in (A), (B), and (C), respectively.

FIGURE 3

The representative image of single‐cell spatial transcriptome. Xenium analysis image of a representative case of early lung adenocarcinoma. Visualization was performed using Xenium Explorer.