Assessing spatial sequencing and imaging approaches to capture the molecular and pathological heterogeneity of archived cancer tissues
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| Format: | Artículo Open Access |
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Wiley
2025
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| author | Tuan Vo P Prakrithi Kahli Jones Sohye Yoon Pui Yeng Lam Yung‐Ching Kao Ning Ma Samuel X Tan Xinnan Jin Chenhao Zhou Joanna Crawford Shaun Walters Ishaan Gupta Peter H Soyer Kiarash Khosrotehrani Mitchell S Stark Quan Nguyen |
| author_facet | Tuan Vo P Prakrithi Kahli Jones Sohye Yoon Pui Yeng Lam Yung‐Ching Kao Ning Ma Samuel X Tan Xinnan Jin Chenhao Zhou Joanna Crawford Shaun Walters Ishaan Gupta Peter H Soyer Kiarash Khosrotehrani Mitchell S Stark Quan Nguyen Tuan Vo P Prakrithi Kahli Jones Sohye Yoon Pui Yeng Lam Yung‐Ching Kao Ning Ma Samuel X Tan Xinnan Jin Chenhao Zhou Joanna Crawford Shaun Walters Ishaan Gupta Peter H Soyer Kiarash Khosrotehrani Mitchell S Stark Quan Nguyen |
| collection | Wiley Open Access |
| contents | Assessing spatial sequencing and imaging approaches to capture the molecular and pathological heterogeneity of archived cancer tissues Tuan Vo P Prakrithi Kahli Jones Sohye Yoon Pui Yeng Lam Yung‐Ching Kao Ning Ma Samuel X Tan Xinnan Jin Chenhao Zhou Joanna Crawford Shaun Walters Ishaan Gupta Peter H Soyer Kiarash Khosrotehrani Mitchell S Stark Quan Nguyen The Journal of Pathology Abstract Spatial transcriptomics (ST) offers enormous potential to decipher the biological and pathological heterogeneity in precious archival cancer tissues. Traditionally, these tissues have rarely been used and only examined at a low throughput, most commonly by histopathological staining. ST adds thousands of times as many molecular features to histopathological images, but critical technical issues and limitations require more assessment of how ST performs on fixed archival tissues. In this work, we addressed this in a cancer‐heterogeneity pipeline, starting with an exploration of the whole transcriptome by two sequencing‐based ST protocols capable of measuring coding and non‐coding RNAs. We optimised the two protocols to work with challenging formalin‐fixed paraffin‐embedded (FFPE) tissues, derived from skin. We then assessed alternative imaging methods, including multiplex RNAScope single‐molecule imaging and multiplex protein imaging (CODEX). We evaluated the methods’ performance for tissues stored from 4 to 14 years ago, covering a range of RNA qualities, allowing us to assess variation. In addition to technical performance metrics, we determined the ability of these methods to quantify tumour heterogeneity. We integrated gene expression profiles with pathological information, charting a new molecular landscape on the pathologically defined tissue regions. Together, this work provides important and comprehensive experimental technical perspectives to consider the applications of ST in deciphering the cancer heterogeneity in archived tissues. © 2025 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland. 10.1002/path.6383 http://creativecommons.org/licenses/by/4.0/ |
| doi_str_mv | 10.1002/path.6383 |
| format | Artículo Open Access |
| id | wiley_oa_10_1002_path_6383 |
| institution | Wiley Open Access |
| license_str_mv | http://creativecommons.org/licenses/by/4.0/ |
| publishDate | 2025 |
| publisher | Wiley |
| record_format | wiley_oa |
| spellingShingle | Assessing spatial sequencing and imaging approaches to capture the molecular and pathological heterogeneity of archived cancer tissues Tuan Vo P Prakrithi Kahli Jones Sohye Yoon Pui Yeng Lam Yung‐Ching Kao Ning Ma Samuel X Tan Xinnan Jin Chenhao Zhou Joanna Crawford Shaun Walters Ishaan Gupta Peter H Soyer Kiarash Khosrotehrani Mitchell S Stark Quan Nguyen The Journal of Pathology Assessing spatial sequencing and imaging approaches to capture the molecular and pathological heterogeneity of archived cancer tissues Tuan Vo P Prakrithi Kahli Jones Sohye Yoon Pui Yeng Lam Yung‐Ching Kao Ning Ma Samuel X Tan Xinnan Jin Chenhao Zhou Joanna Crawford Shaun Walters Ishaan Gupta Peter H Soyer Kiarash Khosrotehrani Mitchell S Stark Quan Nguyen The Journal of Pathology Abstract Spatial transcriptomics (ST) offers enormous potential to decipher the biological and pathological heterogeneity in precious archival cancer tissues. Traditionally, these tissues have rarely been used and only examined at a low throughput, most commonly by histopathological staining. ST adds thousands of times as many molecular features to histopathological images, but critical technical issues and limitations require more assessment of how ST performs on fixed archival tissues. In this work, we addressed this in a cancer‐heterogeneity pipeline, starting with an exploration of the whole transcriptome by two sequencing‐based ST protocols capable of measuring coding and non‐coding RNAs. We optimised the two protocols to work with challenging formalin‐fixed paraffin‐embedded (FFPE) tissues, derived from skin. We then assessed alternative imaging methods, including multiplex RNAScope single‐molecule imaging and multiplex protein imaging (CODEX). We evaluated the methods’ performance for tissues stored from 4 to 14 years ago, covering a range of RNA qualities, allowing us to assess variation. In addition to technical performance metrics, we determined the ability of these methods to quantify tumour heterogeneity. We integrated gene expression profiles with pathological information, charting a new molecular landscape on the pathologically defined tissue regions. Together, this work provides important and comprehensive experimental technical perspectives to consider the applications of ST in deciphering the cancer heterogeneity in archived tissues. © 2025 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland. 10.1002/path.6383 http://creativecommons.org/licenses/by/4.0/ |
| title | Assessing spatial sequencing and imaging approaches to capture the molecular and pathological heterogeneity of archived cancer tissues |
| topic | The Journal of Pathology |
| url | https://pathsocjournals.onlinelibrary.wiley.com/doi/10.1002/path.6383 |