Novel CAF-identifiers via transcriptomic and protein level analysis in HNSC patients
Abstract Cancer-associated fibroblasts (CAFs), a prominent component of the tumor microenvironment, play an important role in tumor development, invasion, and drug resistance. The expression of distinct “CAF-markers” which separates CAFs from normal fibroblasts and epithelial cells, have traditional...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-08-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-40908-w |
| _version_ | 1797559692459769856 |
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| author | Nehanjali Dwivedi Nidhi Shukla K. M. Prathima Manjula Das Sujan K. Dhar |
| author_facet | Nehanjali Dwivedi Nidhi Shukla K. M. Prathima Manjula Das Sujan K. Dhar |
| author_sort | Nehanjali Dwivedi |
| collection | DOAJ |
| description | Abstract Cancer-associated fibroblasts (CAFs), a prominent component of the tumor microenvironment, play an important role in tumor development, invasion, and drug resistance. The expression of distinct “CAF-markers” which separates CAFs from normal fibroblasts and epithelial cells, have traditionally been used to identify them. These commonly used CAF-markers have been reported to differ greatly across different CAF subpopulations, even within a cancer type. Using an unbiased -omic approach from public data and in-house RNAseq data from patient derived novel CAF cells, TIMP-1, SPARC, COL1A2, COL3A1 and COL1A1 were identified as potential CAF-markers by differential gene expression analysis using publicly available single cell sequencing data and in-house RNAseq data to distinguish CAF populations from tumor epithelia and normal oral fibroblasts. Experimental validation using qPCR and immunofluorescence revealed CAF-specific higher expression of TIMP-1 and COL1A2 as compared to other markers in 5 novel CAF cells, derived from patients of diverse gender, habits and different locations of head and neck squamous cell carcinoma (HNSC). Upon immunohistochemical (IHC) analysis of FFPE blocks however, COL1A2 showed better differential staining between tumor epithelia and tumor stroma. Similar data science driven approach utilizing single cell sequencing and RNAseq data from stabilized CAFs can be employed to identify CAF-markers in various cancers. |
| first_indexed | 2024-03-10T17:49:57Z |
| format | Article |
| id | doaj.art-79c66f40e71b41208b53623198ac7b68 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-03-10T17:49:57Z |
| publishDate | 2023-08-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-79c66f40e71b41208b53623198ac7b682023-11-20T09:24:44ZengNature PortfolioScientific Reports2045-23222023-08-0113111010.1038/s41598-023-40908-wNovel CAF-identifiers via transcriptomic and protein level analysis in HNSC patientsNehanjali Dwivedi0Nidhi Shukla1K. M. Prathima2Manjula Das3Sujan K. Dhar4Molecular Immunology, Mazumdar Shaw Medical Foundation, Narayana Health CityMolecular Immunology, Mazumdar Shaw Medical Foundation, Narayana Health CityManipal HospitalMolecular Immunology, Mazumdar Shaw Medical Foundation, Narayana Health CityComputational Biology, Mazumdar Shaw Medical Foundation, Narayana Health CityAbstract Cancer-associated fibroblasts (CAFs), a prominent component of the tumor microenvironment, play an important role in tumor development, invasion, and drug resistance. The expression of distinct “CAF-markers” which separates CAFs from normal fibroblasts and epithelial cells, have traditionally been used to identify them. These commonly used CAF-markers have been reported to differ greatly across different CAF subpopulations, even within a cancer type. Using an unbiased -omic approach from public data and in-house RNAseq data from patient derived novel CAF cells, TIMP-1, SPARC, COL1A2, COL3A1 and COL1A1 were identified as potential CAF-markers by differential gene expression analysis using publicly available single cell sequencing data and in-house RNAseq data to distinguish CAF populations from tumor epithelia and normal oral fibroblasts. Experimental validation using qPCR and immunofluorescence revealed CAF-specific higher expression of TIMP-1 and COL1A2 as compared to other markers in 5 novel CAF cells, derived from patients of diverse gender, habits and different locations of head and neck squamous cell carcinoma (HNSC). Upon immunohistochemical (IHC) analysis of FFPE blocks however, COL1A2 showed better differential staining between tumor epithelia and tumor stroma. Similar data science driven approach utilizing single cell sequencing and RNAseq data from stabilized CAFs can be employed to identify CAF-markers in various cancers.https://doi.org/10.1038/s41598-023-40908-w |
| spellingShingle | Nehanjali Dwivedi Nidhi Shukla K. M. Prathima Manjula Das Sujan K. Dhar Novel CAF-identifiers via transcriptomic and protein level analysis in HNSC patients Scientific Reports |
| title | Novel CAF-identifiers via transcriptomic and protein level analysis in HNSC patients |
| title_full | Novel CAF-identifiers via transcriptomic and protein level analysis in HNSC patients |
| title_fullStr | Novel CAF-identifiers via transcriptomic and protein level analysis in HNSC patients |
| title_full_unstemmed | Novel CAF-identifiers via transcriptomic and protein level analysis in HNSC patients |
| title_short | Novel CAF-identifiers via transcriptomic and protein level analysis in HNSC patients |
| title_sort | novel caf identifiers via transcriptomic and protein level analysis in hnsc patients |
| url | https://doi.org/10.1038/s41598-023-40908-w |
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