Gene expression profile identifies distinct molecular subtypes and potential therapeutic genes in Merkel cell carcinoma
Merkel cell carcinoma (MCC) is a rare primary cutaneous neoplasm of neuroendocrine carcinoma of the skin. About 80% of the MCC occurs due to Merkel cell polyomavirus (MCPyV) and 20% of the tumors usually occur due to severe UV exposure which is a more aggressive type of MCC. It tends to have an incr...
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doaj-84ac528094c14a3dbb317fce0229d0332020-11-25T03:42:32ZengElsevierTranslational Oncology1936-52332020-11-011311100816Gene expression profile identifies distinct molecular subtypes and potential therapeutic genes in Merkel cell carcinomaUmair Ali Khan Saddozai0Fengling Wang1Yu Cheng2Zhang Lu3Muhammad Usman Akbar4Wan Zhu5Yongqiang Li6Xinying Ji7Xiangqian Guo8Department of Preventive Medicine, Institute of Biomedical Informatics, Cell Signal Transduction Laboratory, Bioinformatics Center, School of Basic Medical Sciences, Henan University, Kaifeng 475004, ChinaDepartment of Preventive Medicine, Institute of Biomedical Informatics, Cell Signal Transduction Laboratory, Bioinformatics Center, School of Basic Medical Sciences, Henan University, Kaifeng 475004, ChinaPharmacy Department, Luoyang maternal and Child Health Hospital, Luoyang 471023, ChinaDepartment of Preventive Medicine, Institute of Biomedical Informatics, Cell Signal Transduction Laboratory, Bioinformatics Center, School of Basic Medical Sciences, Henan University, Kaifeng 475004, ChinaGomal Center of Biochemistry and Biotechnology, Gomal University, Dera Ismail Khan 29050, PakistanDepartment of Anesthesia, Stanford University, 300 Pasteur Drive, Stanford, CA 94305, USADepartment of Preventive Medicine, Institute of Biomedical Informatics, Cell Signal Transduction Laboratory, Bioinformatics Center, School of Basic Medical Sciences, Henan University, Kaifeng 475004, China; Corresponding authors.Department of Preventive Medicine, Institute of Biomedical Informatics, Cell Signal Transduction Laboratory, Bioinformatics Center, School of Basic Medical Sciences, Henan University, Kaifeng 475004, China; Corresponding authors.Department of Preventive Medicine, Institute of Biomedical Informatics, Cell Signal Transduction Laboratory, Bioinformatics Center, School of Basic Medical Sciences, Henan University, Kaifeng 475004, China; Corresponding authors.Merkel cell carcinoma (MCC) is a rare primary cutaneous neoplasm of neuroendocrine carcinoma of the skin. About 80% of the MCC occurs due to Merkel cell polyomavirus (MCPyV) and 20% of the tumors usually occur due to severe UV exposure which is a more aggressive type of MCC. It tends to have an increased incidence rate among elderly and immunosuppressed individuals. On therapeutic level, sub-classification of MCC through molecular subtyping has emerged as a promising technique for MCC prognosis. In current study, two consistent distinct molecular subtypes of MCCs were identified using gene expression profiling data. Subtypes I MCCs were associated with spliceosome, DNA replication and cellular pathways. On the other hand, genes overexpressed in subtype II were found active in TNF signalling pathway and MAPK signalling pathway. We proposed different therapeutic targets based on subtype specificity, such as PTCH1, CDKN2A, AURKA in case of subtype I and MCL1, FGFR2 for subtype II. Such findings may provide fruitful knowledge to understand the intrinsic subtypes of MCCs and the pathways involved in distinct subtype oncogenesis, and will further advance the knowledge in developing a specific therapeutic strategy for these MCC subtypes.http://www.sciencedirect.com/science/article/pii/S1936523320303089Merkel cell carcinomaMolecular subtypeGene expressionSubtype specific treatment |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Umair Ali Khan Saddozai Fengling Wang Yu Cheng Zhang Lu Muhammad Usman Akbar Wan Zhu Yongqiang Li Xinying Ji Xiangqian Guo |
spellingShingle |
Umair Ali Khan Saddozai Fengling Wang Yu Cheng Zhang Lu Muhammad Usman Akbar Wan Zhu Yongqiang Li Xinying Ji Xiangqian Guo Gene expression profile identifies distinct molecular subtypes and potential therapeutic genes in Merkel cell carcinoma Translational Oncology Merkel cell carcinoma Molecular subtype Gene expression Subtype specific treatment |
author_facet |
Umair Ali Khan Saddozai Fengling Wang Yu Cheng Zhang Lu Muhammad Usman Akbar Wan Zhu Yongqiang Li Xinying Ji Xiangqian Guo |
author_sort |
Umair Ali Khan Saddozai |
title |
Gene expression profile identifies distinct molecular subtypes and potential therapeutic genes in Merkel cell carcinoma |
title_short |
Gene expression profile identifies distinct molecular subtypes and potential therapeutic genes in Merkel cell carcinoma |
title_full |
Gene expression profile identifies distinct molecular subtypes and potential therapeutic genes in Merkel cell carcinoma |
title_fullStr |
Gene expression profile identifies distinct molecular subtypes and potential therapeutic genes in Merkel cell carcinoma |
title_full_unstemmed |
Gene expression profile identifies distinct molecular subtypes and potential therapeutic genes in Merkel cell carcinoma |
title_sort |
gene expression profile identifies distinct molecular subtypes and potential therapeutic genes in merkel cell carcinoma |
publisher |
Elsevier |
series |
Translational Oncology |
issn |
1936-5233 |
publishDate |
2020-11-01 |
description |
Merkel cell carcinoma (MCC) is a rare primary cutaneous neoplasm of neuroendocrine carcinoma of the skin. About 80% of the MCC occurs due to Merkel cell polyomavirus (MCPyV) and 20% of the tumors usually occur due to severe UV exposure which is a more aggressive type of MCC. It tends to have an increased incidence rate among elderly and immunosuppressed individuals. On therapeutic level, sub-classification of MCC through molecular subtyping has emerged as a promising technique for MCC prognosis. In current study, two consistent distinct molecular subtypes of MCCs were identified using gene expression profiling data. Subtypes I MCCs were associated with spliceosome, DNA replication and cellular pathways. On the other hand, genes overexpressed in subtype II were found active in TNF signalling pathway and MAPK signalling pathway. We proposed different therapeutic targets based on subtype specificity, such as PTCH1, CDKN2A, AURKA in case of subtype I and MCL1, FGFR2 for subtype II. Such findings may provide fruitful knowledge to understand the intrinsic subtypes of MCCs and the pathways involved in distinct subtype oncogenesis, and will further advance the knowledge in developing a specific therapeutic strategy for these MCC subtypes. |
topic |
Merkel cell carcinoma Molecular subtype Gene expression Subtype specific treatment |
url |
http://www.sciencedirect.com/science/article/pii/S1936523320303089 |
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