One-carbon metabolic pathway is a novel molecular signature for CD44-positive intestinal-type gastric cancer
Abstract Intratumoral heterogeneity (ITH), arising from various factors, plays a crucial role in diverse cancers, yet research on ITH remains in its early stages. To explore this phenomenon further, we conducted single-nuclei transcriptome profiling on patient-derived organoids (PDOs) from two histo...
Saved in:
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2025-08-01
|
| Series: | Cell Death Discovery |
| Online Access: | https://doi.org/10.1038/s41420-025-02704-5 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849226689234599936 |
|---|---|
| author | Seyeon Joo Yoojin Bae Bo Kyung Yoon Yeonjin Je Yuna Kim Minki Kim Su-Jin Shin Sungsoon Fang Jie-Hyun Kim |
| author_facet | Seyeon Joo Yoojin Bae Bo Kyung Yoon Yeonjin Je Yuna Kim Minki Kim Su-Jin Shin Sungsoon Fang Jie-Hyun Kim |
| author_sort | Seyeon Joo |
| collection | DOAJ |
| description | Abstract Intratumoral heterogeneity (ITH), arising from various factors, plays a crucial role in diverse cancers, yet research on ITH remains in its early stages. To explore this phenomenon further, we conducted single-nuclei transcriptome profiling on patient-derived organoids (PDOs) from two histologically pure subtypes of gastric cancer. We identified differences in cancer stem cell marker expression among intestinal-type samples and their correlation with one-carbon (1C) metabolism. Notably, some gastric cancer samples, although histologically classified as intestinal-type, exhibited diffuse-like genetic characteristics. This finding suggests the potential for employing a 1C metabolism inhibition strategy as a therapeutic approach for these genetically diffuse-like gastric cancers. This study highlights the necessity of addressing ITH in PDO-based preclinical models and contributes valuable insights toward advancing precision medicine treatments for gastric cancer. |
| format | Article |
| id | doaj-art-f4724c13d71445df805dfb166683e3f9 |
| institution | Kabale University |
| issn | 2058-7716 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death Discovery |
| spelling | doaj-art-f4724c13d71445df805dfb166683e3f92025-08-24T11:08:20ZengNature Publishing GroupCell Death Discovery2058-77162025-08-0111111410.1038/s41420-025-02704-5One-carbon metabolic pathway is a novel molecular signature for CD44-positive intestinal-type gastric cancerSeyeon Joo0Yoojin Bae1Bo Kyung Yoon2Yeonjin Je3Yuna Kim4Minki Kim5Su-Jin Shin6Sungsoon Fang7Jie-Hyun Kim8Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of MedicineDepartment of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of MedicineDepartment of Microbiology and Immunology, Yonsei University College of MedicineDepartment of Medicine, Yonsei University College of MedicineDepartment of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of MedicineGraduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of MedicineDepartment of Pathology, Gangnam Severance Hospital, Yonsei University College of MedicineGraduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of MedicineDepartment of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of MedicineAbstract Intratumoral heterogeneity (ITH), arising from various factors, plays a crucial role in diverse cancers, yet research on ITH remains in its early stages. To explore this phenomenon further, we conducted single-nuclei transcriptome profiling on patient-derived organoids (PDOs) from two histologically pure subtypes of gastric cancer. We identified differences in cancer stem cell marker expression among intestinal-type samples and their correlation with one-carbon (1C) metabolism. Notably, some gastric cancer samples, although histologically classified as intestinal-type, exhibited diffuse-like genetic characteristics. This finding suggests the potential for employing a 1C metabolism inhibition strategy as a therapeutic approach for these genetically diffuse-like gastric cancers. This study highlights the necessity of addressing ITH in PDO-based preclinical models and contributes valuable insights toward advancing precision medicine treatments for gastric cancer.https://doi.org/10.1038/s41420-025-02704-5 |
| spellingShingle | Seyeon Joo Yoojin Bae Bo Kyung Yoon Yeonjin Je Yuna Kim Minki Kim Su-Jin Shin Sungsoon Fang Jie-Hyun Kim One-carbon metabolic pathway is a novel molecular signature for CD44-positive intestinal-type gastric cancer Cell Death Discovery |
| title | One-carbon metabolic pathway is a novel molecular signature for CD44-positive intestinal-type gastric cancer |
| title_full | One-carbon metabolic pathway is a novel molecular signature for CD44-positive intestinal-type gastric cancer |
| title_fullStr | One-carbon metabolic pathway is a novel molecular signature for CD44-positive intestinal-type gastric cancer |
| title_full_unstemmed | One-carbon metabolic pathway is a novel molecular signature for CD44-positive intestinal-type gastric cancer |
| title_short | One-carbon metabolic pathway is a novel molecular signature for CD44-positive intestinal-type gastric cancer |
| title_sort | one carbon metabolic pathway is a novel molecular signature for cd44 positive intestinal type gastric cancer |
| url | https://doi.org/10.1038/s41420-025-02704-5 |
| work_keys_str_mv | AT seyeonjoo onecarbonmetabolicpathwayisanovelmolecularsignatureforcd44positiveintestinaltypegastriccancer AT yoojinbae onecarbonmetabolicpathwayisanovelmolecularsignatureforcd44positiveintestinaltypegastriccancer AT bokyungyoon onecarbonmetabolicpathwayisanovelmolecularsignatureforcd44positiveintestinaltypegastriccancer AT yeonjinje onecarbonmetabolicpathwayisanovelmolecularsignatureforcd44positiveintestinaltypegastriccancer AT yunakim onecarbonmetabolicpathwayisanovelmolecularsignatureforcd44positiveintestinaltypegastriccancer AT minkikim onecarbonmetabolicpathwayisanovelmolecularsignatureforcd44positiveintestinaltypegastriccancer AT sujinshin onecarbonmetabolicpathwayisanovelmolecularsignatureforcd44positiveintestinaltypegastriccancer AT sungsoonfang onecarbonmetabolicpathwayisanovelmolecularsignatureforcd44positiveintestinaltypegastriccancer AT jiehyunkim onecarbonmetabolicpathwayisanovelmolecularsignatureforcd44positiveintestinaltypegastriccancer |