Michelle G. Zhang , Ryan A. Gallo , Charissa H. Tan , Matthew Camacho , Sohaib Fasih-Ahmad , Acadia H.M. Moeyersoms , Yoseph Sayegh , Sander R. Dubovy , Daniel Pelaez , Andrew J. Rong
{"title":"眼附属皮脂腺癌的单细胞 RNA 图谱揭示了复杂的肿瘤微环境,并确定了新的生物标记物。","authors":"Michelle G. Zhang , Ryan A. Gallo , Charissa H. Tan , Matthew Camacho , Sohaib Fasih-Ahmad , Acadia H.M. Moeyersoms , Yoseph Sayegh , Sander R. Dubovy , Daniel Pelaez , Andrew J. Rong","doi":"10.1016/j.ajo.2024.10.001","DOIUrl":null,"url":null,"abstract":"<div><h3>Purpose</h3><div>Ocular adnexal sebaceous carcinoma (OaSC) is an aggressive malignancy that often necessitates orbital exenteration. Its tumor composition and transcriptional profile remain largely unknown, which poses a significant barrier to medical advances. Here, we report the first in-depth transcriptomic analysis of OaSC at the single-cell resolution and discern mechanisms underlying cancer progression for the discovery of potential globe-sparing immunotherapies, targeted therapies, and biomarkers to guide clinical management.</div></div><div><h3>Design</h3><div>Laboratory investigation with a retrospective observational case series.</div></div><div><h3>Methods</h3><div>Single-cell RNA sequencing was performed on six patient specimens: three primary tumors, two tumors with pagetoid spread, and a normal tarsus sample. Cellular components were identified via gene signatures. Molecular pathways underlying tumorigenesis and pagetoid spread were discerned via gene ontology analysis of the differentially expressed genes between specimens. CALML5 immunohistochemistry was performed on an archival cohort of OaSC, squamous cell carcinoma, ocular surface squamous neoplasia (OSSN), and basal cell carcinoma cases.</div></div><div><h3>Results</h3><div>Analysis of 29,219 cells from OaSC specimens revealed tumor, immune, and stromal cells. Tumor-infiltrating immune cells include a diversity of cell types, including exhausted T-cell populations. In primary OaSC tumors, mitotic nuclear division and oxidative phosphorylation pathways are upregulated, while lipid biosynthesis and metabolism pathways are downregulated. Epithelial tissue migration pathways are upregulated in tumor cells undergoing pagetoid spread. Single-cell RNA sequencing analyses also revealed that CALML5 is upregulated in OaSC tumor cells. Diffuse nuclear and cytoplasmic CALML5 staining was present in 28 of 28 (100%) OaSC cases. Diffuse nuclear and membranous CALML5 staining was present in 5 of 25 (20%) squamous cell carcinoma and OSSN cases, while diffuse nuclear staining was present in 1 of 12 (8%) basal cell carcinoma cases.</div></div><div><h3>Conclusions</h3><div>This study reveals a complex OaSC tumor microenvironment and confirms that the CALML5 immunohistochemical stain is a sensitive diagnostic marker.</div></div>","PeriodicalId":7568,"journal":{"name":"American Journal of Ophthalmology","volume":"270 ","pages":"Pages 8-18"},"PeriodicalIF":4.1000,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Single-Cell RNA Profiling of Ocular Adnexal Sebaceous Carcinoma Reveals a Complex Tumor Microenvironment and Identifies New Biomarkers\",\"authors\":\"Michelle G. Zhang , Ryan A. Gallo , Charissa H. Tan , Matthew Camacho , Sohaib Fasih-Ahmad , Acadia H.M. Moeyersoms , Yoseph Sayegh , Sander R. Dubovy , Daniel Pelaez , Andrew J. Rong\",\"doi\":\"10.1016/j.ajo.2024.10.001\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Purpose</h3><div>Ocular adnexal sebaceous carcinoma (OaSC) is an aggressive malignancy that often necessitates orbital exenteration. Its tumor composition and transcriptional profile remain largely unknown, which poses a significant barrier to medical advances. Here, we report the first in-depth transcriptomic analysis of OaSC at the single-cell resolution and discern mechanisms underlying cancer progression for the discovery of potential globe-sparing immunotherapies, targeted therapies, and biomarkers to guide clinical management.</div></div><div><h3>Design</h3><div>Laboratory investigation with a retrospective observational case series.</div></div><div><h3>Methods</h3><div>Single-cell RNA sequencing was performed on six patient specimens: three primary tumors, two tumors with pagetoid spread, and a normal tarsus sample. Cellular components were identified via gene signatures. Molecular pathways underlying tumorigenesis and pagetoid spread were discerned via gene ontology analysis of the differentially expressed genes between specimens. CALML5 immunohistochemistry was performed on an archival cohort of OaSC, squamous cell carcinoma, ocular surface squamous neoplasia (OSSN), and basal cell carcinoma cases.</div></div><div><h3>Results</h3><div>Analysis of 29,219 cells from OaSC specimens revealed tumor, immune, and stromal cells. Tumor-infiltrating immune cells include a diversity of cell types, including exhausted T-cell populations. In primary OaSC tumors, mitotic nuclear division and oxidative phosphorylation pathways are upregulated, while lipid biosynthesis and metabolism pathways are downregulated. Epithelial tissue migration pathways are upregulated in tumor cells undergoing pagetoid spread. Single-cell RNA sequencing analyses also revealed that CALML5 is upregulated in OaSC tumor cells. Diffuse nuclear and cytoplasmic CALML5 staining was present in 28 of 28 (100%) OaSC cases. Diffuse nuclear and membranous CALML5 staining was present in 5 of 25 (20%) squamous cell carcinoma and OSSN cases, while diffuse nuclear staining was present in 1 of 12 (8%) basal cell carcinoma cases.</div></div><div><h3>Conclusions</h3><div>This study reveals a complex OaSC tumor microenvironment and confirms that the CALML5 immunohistochemical stain is a sensitive diagnostic marker.</div></div>\",\"PeriodicalId\":7568,\"journal\":{\"name\":\"American Journal of Ophthalmology\",\"volume\":\"270 \",\"pages\":\"Pages 8-18\"},\"PeriodicalIF\":4.1000,\"publicationDate\":\"2024-10-10\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"American Journal of Ophthalmology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0002939424004719\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"OPHTHALMOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"American Journal of Ophthalmology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0002939424004719","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"OPHTHALMOLOGY","Score":null,"Total":0}
Single-Cell RNA Profiling of Ocular Adnexal Sebaceous Carcinoma Reveals a Complex Tumor Microenvironment and Identifies New Biomarkers
Purpose
Ocular adnexal sebaceous carcinoma (OaSC) is an aggressive malignancy that often necessitates orbital exenteration. Its tumor composition and transcriptional profile remain largely unknown, which poses a significant barrier to medical advances. Here, we report the first in-depth transcriptomic analysis of OaSC at the single-cell resolution and discern mechanisms underlying cancer progression for the discovery of potential globe-sparing immunotherapies, targeted therapies, and biomarkers to guide clinical management.
Design
Laboratory investigation with a retrospective observational case series.
Methods
Single-cell RNA sequencing was performed on six patient specimens: three primary tumors, two tumors with pagetoid spread, and a normal tarsus sample. Cellular components were identified via gene signatures. Molecular pathways underlying tumorigenesis and pagetoid spread were discerned via gene ontology analysis of the differentially expressed genes between specimens. CALML5 immunohistochemistry was performed on an archival cohort of OaSC, squamous cell carcinoma, ocular surface squamous neoplasia (OSSN), and basal cell carcinoma cases.
Results
Analysis of 29,219 cells from OaSC specimens revealed tumor, immune, and stromal cells. Tumor-infiltrating immune cells include a diversity of cell types, including exhausted T-cell populations. In primary OaSC tumors, mitotic nuclear division and oxidative phosphorylation pathways are upregulated, while lipid biosynthesis and metabolism pathways are downregulated. Epithelial tissue migration pathways are upregulated in tumor cells undergoing pagetoid spread. Single-cell RNA sequencing analyses also revealed that CALML5 is upregulated in OaSC tumor cells. Diffuse nuclear and cytoplasmic CALML5 staining was present in 28 of 28 (100%) OaSC cases. Diffuse nuclear and membranous CALML5 staining was present in 5 of 25 (20%) squamous cell carcinoma and OSSN cases, while diffuse nuclear staining was present in 1 of 12 (8%) basal cell carcinoma cases.
Conclusions
This study reveals a complex OaSC tumor microenvironment and confirms that the CALML5 immunohistochemical stain is a sensitive diagnostic marker.
期刊介绍:
The American Journal of Ophthalmology is a peer-reviewed, scientific publication that welcomes the submission of original, previously unpublished manuscripts directed to ophthalmologists and visual science specialists describing clinical investigations, clinical observations, and clinically relevant laboratory investigations. Published monthly since 1884, the full text of the American Journal of Ophthalmology and supplementary material are also presented online at www.AJO.com and on ScienceDirect.
The American Journal of Ophthalmology publishes Full-Length Articles, Perspectives, Editorials, Correspondences, Books Reports and Announcements. Brief Reports and Case Reports are no longer published. We recommend submitting Brief Reports and Case Reports to our companion publication, the American Journal of Ophthalmology Case Reports.
Manuscripts are accepted with the understanding that they have not been and will not be published elsewhere substantially in any format, and that there are no ethical problems with the content or data collection. Authors may be requested to produce the data upon which the manuscript is based and to answer expeditiously any questions about the manuscript or its authors.