Identification of cancer-associated fibrolast subtypes and distinctive role of MFAP5 in CT-detected extramural venous invasion in gastric cancer
Extramural venous invasion (EMVI) detected by computed tomography has been identified as an independent risk factor for distant metastasis in patients with advanced gastric cancer (GC). Cancer-associated fibroblasts (CAFs) are critical for remodeling the tumor microenvironment in GCs. Here, we repor...
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| Format: | Article |
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Elsevier
2025-01-01
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| Series: | Translational Oncology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1936523324003140 |
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| author | Bo Gao Xinyi Gou Caizhen Feng Yinli Zhang Huining Gu Fan Chai Yi Wang Yingjiang Ye Nan Hong Guohua Hu Boshi Sun Jin Cheng Hao Yang |
| author_facet | Bo Gao Xinyi Gou Caizhen Feng Yinli Zhang Huining Gu Fan Chai Yi Wang Yingjiang Ye Nan Hong Guohua Hu Boshi Sun Jin Cheng Hao Yang |
| author_sort | Bo Gao |
| collection | DOAJ |
| description | Extramural venous invasion (EMVI) detected by computed tomography has been identified as an independent risk factor for distant metastasis in patients with advanced gastric cancer (GC). Cancer-associated fibroblasts (CAFs) are critical for remodeling the tumor microenvironment in GCs. Here, we report that MFAP5+ CAFs promote the formation of EMVI imaging in GC. We detected gene expression in pathological samples from 13 advanced GC patients with EMVI. Radiogenomics results showed the degree of CAFs infiltration was directly proportional to the EMVI score and EMT pathway in GC patients. Single-cell sequencing data analysis results showed that MFAP5+CAFs subtypes in GC were negatively correlated with patient prognosis and were enriched in tumor lactylation modification and EMT pathways. Immunohistochemistry results showed that the expression of MFAP5, L-lactyl and EMT markers in GC tissues was proportional to the EMVI score. CAF from gastric cancer tissue was extracted using collagenase method and co-cultured with GC cell line in vitro. After lentivirus knockdown of MFAP5 in CAFs, the levels of L-lactoyl and histone lactylation modifications were significantly reduced, and the sphere-forming and vascularization abilities of CAFs were significantly inhibited. Cell function experiments showed that MFAP5+ CAFs can affect the EMT, metastasis and invasion capabilities of GC cells. In vivo experimental results of the nude mouse in situ EMVI model suggest that MFAP5+ CAF may promote the formation of EMVI imaging features in GC by regulating lactylation modification. This innovative work may provide important new references for the diagnosis and treatment of GC. |
| format | Article |
| id | doaj-art-e65d5f029bed46faa05e657a236575dc |
| institution | Kabale University |
| issn | 1936-5233 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Translational Oncology |
| spelling | doaj-art-e65d5f029bed46faa05e657a236575dc2024-12-09T04:27:07ZengElsevierTranslational Oncology1936-52332025-01-0151102188Identification of cancer-associated fibrolast subtypes and distinctive role of MFAP5 in CT-detected extramural venous invasion in gastric cancerBo Gao0Xinyi Gou1Caizhen Feng2Yinli Zhang3Huining Gu4Fan Chai5Yi Wang6Yingjiang Ye7Nan Hong8Guohua Hu9Boshi Sun10Jin Cheng11Hao Yang12Department of Hernia and Abdominal Wall Surgery, Peking University People's Hospital, Peking University Health Science Center, Beijing, ChinaDepartment of Radiology, Peking University People's Hospital, Peking University Health Science Center, Beijing, ChinaDepartment of Radiology, Peking University People's Hospital, Peking University Health Science Center, Beijing, ChinaDepartment of Pathology, Peking University People's Hospital, Peking University Health Science Center, Beijing, ChinaDepartment of Immunology, School of Basic Medical Sciences, Peking University and NHC Key Laboratory of Medical Immunology, Peking University, Beijing, ChinaDepartment of Radiology, Peking University People's Hospital, Peking University Health Science Center, Beijing, ChinaDepartment of Radiology, Peking University People's Hospital, Peking University Health Science Center, Beijing, ChinaDepartment of Gastrointestinal Surgery, Peking University People's Hospital, Peking University Health Science Center, Beijing, ChinaDepartment of Radiology, Peking University People's Hospital, Peking University Health Science Center, Beijing, ChinaDepartment of Hernia and Abdominal Wall Surgery, Peking University People's Hospital, Peking University Health Science Center, Beijing, ChinaDepartment of General Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, China; Corresponding authors.Department of Radiology, Peking University People's Hospital, Peking University Health Science Center, Beijing, China; Corresponding authors.Department of Oncology Surgery, Harbin Medical University Cancer Hospital, Harbin, China; Corresponding authors.Extramural venous invasion (EMVI) detected by computed tomography has been identified as an independent risk factor for distant metastasis in patients with advanced gastric cancer (GC). Cancer-associated fibroblasts (CAFs) are critical for remodeling the tumor microenvironment in GCs. Here, we report that MFAP5+ CAFs promote the formation of EMVI imaging in GC. We detected gene expression in pathological samples from 13 advanced GC patients with EMVI. Radiogenomics results showed the degree of CAFs infiltration was directly proportional to the EMVI score and EMT pathway in GC patients. Single-cell sequencing data analysis results showed that MFAP5+CAFs subtypes in GC were negatively correlated with patient prognosis and were enriched in tumor lactylation modification and EMT pathways. Immunohistochemistry results showed that the expression of MFAP5, L-lactyl and EMT markers in GC tissues was proportional to the EMVI score. CAF from gastric cancer tissue was extracted using collagenase method and co-cultured with GC cell line in vitro. After lentivirus knockdown of MFAP5 in CAFs, the levels of L-lactoyl and histone lactylation modifications were significantly reduced, and the sphere-forming and vascularization abilities of CAFs were significantly inhibited. Cell function experiments showed that MFAP5+ CAFs can affect the EMT, metastasis and invasion capabilities of GC cells. In vivo experimental results of the nude mouse in situ EMVI model suggest that MFAP5+ CAF may promote the formation of EMVI imaging features in GC by regulating lactylation modification. This innovative work may provide important new references for the diagnosis and treatment of GC.http://www.sciencedirect.com/science/article/pii/S1936523324003140Gastric cancerTumor microenviromentMFAP5+ cancer-associated fibroblastsLactylation modificationExtramural venous invasion |
| spellingShingle | Bo Gao Xinyi Gou Caizhen Feng Yinli Zhang Huining Gu Fan Chai Yi Wang Yingjiang Ye Nan Hong Guohua Hu Boshi Sun Jin Cheng Hao Yang Identification of cancer-associated fibrolast subtypes and distinctive role of MFAP5 in CT-detected extramural venous invasion in gastric cancer Translational Oncology Gastric cancer Tumor microenviroment MFAP5+ cancer-associated fibroblasts Lactylation modification Extramural venous invasion |
| title | Identification of cancer-associated fibrolast subtypes and distinctive role of MFAP5 in CT-detected extramural venous invasion in gastric cancer |
| title_full | Identification of cancer-associated fibrolast subtypes and distinctive role of MFAP5 in CT-detected extramural venous invasion in gastric cancer |
| title_fullStr | Identification of cancer-associated fibrolast subtypes and distinctive role of MFAP5 in CT-detected extramural venous invasion in gastric cancer |
| title_full_unstemmed | Identification of cancer-associated fibrolast subtypes and distinctive role of MFAP5 in CT-detected extramural venous invasion in gastric cancer |
| title_short | Identification of cancer-associated fibrolast subtypes and distinctive role of MFAP5 in CT-detected extramural venous invasion in gastric cancer |
| title_sort | identification of cancer associated fibrolast subtypes and distinctive role of mfap5 in ct detected extramural venous invasion in gastric cancer |
| topic | Gastric cancer Tumor microenviroment MFAP5+ cancer-associated fibroblasts Lactylation modification Extramural venous invasion |
| url | http://www.sciencedirect.com/science/article/pii/S1936523324003140 |
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