Combined spatial Keratin expression profiles at the invasive front represent a prognostic classifier for head and neck cancer
Keratin proteins are intermediate filaments that provide mechanical support and guide a plethora of important functions in epithelial cells. Although Keratins can be effectively used to characterize and differentiate cell lineages in many epithelia, it is still unclear if combinations of Keratin typ...
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Elsevier
2024-06-01
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| Series: | Oral Oncology Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2772906024002401 |
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| author | Peter D. Haughton Wisse E. Haakma Sven van Kempen Emma J. de Ruiter Stefan M. Willems Patrick W.B. Derksen |
| author_facet | Peter D. Haughton Wisse E. Haakma Sven van Kempen Emma J. de Ruiter Stefan M. Willems Patrick W.B. Derksen |
| author_sort | Peter D. Haughton |
| collection | DOAJ |
| description | Keratin proteins are intermediate filaments that provide mechanical support and guide a plethora of important functions in epithelial cells. Although Keratins can be effectively used to characterize and differentiate cell lineages in many epithelia, it is still unclear if combinations of Keratin types and their spatial expression patterns can aid prognostication of head and neck squamous cell carcinoma (HNSCC). Here, we have assessed a panel of Keratin markers in four HPV negative HNSCC patient-derived organoid (PDO) models and their corresponding primary patient tissue to define spatial expression profiles of basal and supra-basal Keratins during invasion in Collagen-I matrices. Based on these profiles we have devised a scoring classification consisting of the following profiles: (i) no expression (Negative), (ii) uniform expression (Homogenous), (iii) heterogeneous expression (Mosaic), (iv) expression in the tumor core (Core), and (v) expression at the invasive front (Edge). Subsequently, this 5-tier system was validated in a well-documented tissue cohort of 157 HNSCC patients. We observe that patients with a Keratin 13 (K13) Edge profile have a significantly better prognosis than patients with K13 Core expression or K13 Negative tumors. Interestingly, we also find that K14 mosaicism strongly correlates with a favorable prognosis. We show that the absence of K13 from the tumor edge, in combination with K14 homogenous expression is a strong biomarker for poor prognosis in HNSCC. In short, our work indicates that defining the spatial expression patterns of basal and supra-basal markers in invasive HNSCC can benefit patient prognostication. |
| format | Article |
| id | doaj-art-6f72331067d14bde9f2b95b30bc56274 |
| institution | Kabale University |
| issn | 2772-9060 |
| language | English |
| publishDate | 2024-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Oral Oncology Reports |
| spelling | doaj-art-6f72331067d14bde9f2b95b30bc562742025-01-09T06:16:04ZengElsevierOral Oncology Reports2772-90602024-06-0110100394Combined spatial Keratin expression profiles at the invasive front represent a prognostic classifier for head and neck cancerPeter D. Haughton0Wisse E. Haakma1Sven van Kempen2Emma J. de Ruiter3Stefan M. Willems4Patrick W.B. Derksen5Department of Pathology, University Medical Centre Utrecht, Utrecht, the NetherlandsDepartment of Pathology, University Medical Centre Utrecht, Utrecht, the NetherlandsDepartment of Pathology, University Medical Centre Utrecht, Utrecht, the NetherlandsDepartment of Pathology, University Medical Centre Utrecht, Utrecht, the NetherlandsDepartment Pathology and Medical Biology, University Medical Centre Groningen, Groningen, the Netherlands; Corresponding author. UMC Groningen, Dept. of Pathology and Medical Biology, Hanzeplein 1, 9713 GZ, Groningen, the Netherlands.Department of Pathology, University Medical Centre Utrecht, Utrecht, the Netherlands; Corresponding author. UMC Utrecht, Dept. of Pathology, Heidelberglaan 100, 3584CX, Utrecht, the Netherlands.Keratin proteins are intermediate filaments that provide mechanical support and guide a plethora of important functions in epithelial cells. Although Keratins can be effectively used to characterize and differentiate cell lineages in many epithelia, it is still unclear if combinations of Keratin types and their spatial expression patterns can aid prognostication of head and neck squamous cell carcinoma (HNSCC). Here, we have assessed a panel of Keratin markers in four HPV negative HNSCC patient-derived organoid (PDO) models and their corresponding primary patient tissue to define spatial expression profiles of basal and supra-basal Keratins during invasion in Collagen-I matrices. Based on these profiles we have devised a scoring classification consisting of the following profiles: (i) no expression (Negative), (ii) uniform expression (Homogenous), (iii) heterogeneous expression (Mosaic), (iv) expression in the tumor core (Core), and (v) expression at the invasive front (Edge). Subsequently, this 5-tier system was validated in a well-documented tissue cohort of 157 HNSCC patients. We observe that patients with a Keratin 13 (K13) Edge profile have a significantly better prognosis than patients with K13 Core expression or K13 Negative tumors. Interestingly, we also find that K14 mosaicism strongly correlates with a favorable prognosis. We show that the absence of K13 from the tumor edge, in combination with K14 homogenous expression is a strong biomarker for poor prognosis in HNSCC. In short, our work indicates that defining the spatial expression patterns of basal and supra-basal markers in invasive HNSCC can benefit patient prognostication.http://www.sciencedirect.com/science/article/pii/S2772906024002401KeratinSpatial expression profilesHead and neck cancerPatient derived tumor organoidsInvasion |
| spellingShingle | Peter D. Haughton Wisse E. Haakma Sven van Kempen Emma J. de Ruiter Stefan M. Willems Patrick W.B. Derksen Combined spatial Keratin expression profiles at the invasive front represent a prognostic classifier for head and neck cancer Oral Oncology Reports Keratin Spatial expression profiles Head and neck cancer Patient derived tumor organoids Invasion |
| title | Combined spatial Keratin expression profiles at the invasive front represent a prognostic classifier for head and neck cancer |
| title_full | Combined spatial Keratin expression profiles at the invasive front represent a prognostic classifier for head and neck cancer |
| title_fullStr | Combined spatial Keratin expression profiles at the invasive front represent a prognostic classifier for head and neck cancer |
| title_full_unstemmed | Combined spatial Keratin expression profiles at the invasive front represent a prognostic classifier for head and neck cancer |
| title_short | Combined spatial Keratin expression profiles at the invasive front represent a prognostic classifier for head and neck cancer |
| title_sort | combined spatial keratin expression profiles at the invasive front represent a prognostic classifier for head and neck cancer |
| topic | Keratin Spatial expression profiles Head and neck cancer Patient derived tumor organoids Invasion |
| url | http://www.sciencedirect.com/science/article/pii/S2772906024002401 |
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